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Ye H, Liu R, Cao P, Guo Q, Chen W, Mao H, Yang X. Peritoneal protein clearance, fluid overload, and cardiovascular events in patients undergoing peritoneal dialysis: a prospective cohort study. Ren Fail 2025; 47:2461676. [PMID: 39962729 PMCID: PMC11837914 DOI: 10.1080/0886022x.2025.2461676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 01/24/2025] [Accepted: 01/28/2025] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND The relationship among higher peritoneal protein clearance (PPCl), fluid overload, and increased risk of cardiovascular (CV) events has not been well clarified in peritoneal dialysis (PD) patients. We aimed to examine their associations in a prospective cohort study. METHODS Eligible patients were enrolled from a single center, and PPCl was calculated based on the daily dialysate protein loss corrected for serum albumin. Fluid overload was defined as extracellular water (ECW)/total body water (TBW) ≥0.400 measured by bioelectrical impedance analysis (BIA). The primary outcome was CV events. RESULTS In total, 351 patients were included in this study. After adjustment for confounders, every 5 mL/day increase in PPCl was independently associated with a 27% higher risk of fluid overload determined by BIA (odds ratio: 1.27, 95% confidence interval (CI): 1.17-1.37). After a median follow-up of 46.8 months, 90 patients (25.6%) experienced CV events. In competing risk models adjusted for confounders, both fluid overload and every 5 mL/day increase in PPCl were independently associated with 70% (subdistribution hazard ratio (SHR):1.70, 95%CI: 1.06-2.74) and 9% (SHR: 1.09, 95%CI: 1.04-1.14) increased risk of CV events, respectively. When fluid overload and PPCl were added simultaneously to the models, PPCl remained a strong independent predictor (SHR: 1.07; 95%CI: 1.03-1.13). CONCLUSIONS Higher PPCl was independently associated with fluid overload determined by BIA in PD patients. Moreover, higher PPCl was independently associated with an increased risk of CV events.
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Affiliation(s)
- Hongjian Ye
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Ruihua Liu
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Peiyi Cao
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Qunying Guo
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Wei Chen
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Haiping Mao
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Xiao Yang
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
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Xu T, Ruan Y, Liu N, Wang Y, Zang X, Ma Y, Qi H, Mi X, Yu G, Zhang C, Huang X, Xie J, Chen N, Ren H. Effect of roxadustat on lowering blood lipids in peritoneal dialysis patients with anemia. Ren Fail 2025; 47:2460726. [PMID: 40000368 PMCID: PMC11864003 DOI: 10.1080/0886022x.2025.2460726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 01/21/2025] [Accepted: 01/26/2025] [Indexed: 02/27/2025] Open
Abstract
OBJECTIVES To observe the effect of roxadustat on lowering blood lipids in peritoneal dialysis (PD) patients beyond treating anemia. METHODS In a prospective, multicenter clinical study, we randomly assigned (in a 1:1 ratio) 100 PD patients who had received erythropoiesis-stimulating agent therapy for at least 4 weeks to receive either roxadustat or erythropoietin (EPO) for 48 weeks. The blood lipids, hemoglobin, blood pressure, blood glucose, iron metabolism and inflammatory factors were compared between the two groups at 0, 2, 4, 8, 12, 16, 20, 24 and 48 weeks, respectively. RESULTS At start of switching to roxadustat, hemoglobin seemed to rise a little faster (102.8 ± 15.4 vs. 97.1 ± 17.3 g/L at 2 weeks, p > 0.05), but there was no significant difference in hemoglobin change between the two groups over the course of observation (p = 0.185). At the early stage of the study (12 weeks), the transferrin saturation (TSAT) of roxadustat group decreased significantly from the baseline (32.7 (20.6) vs. 22.1 (18.7)%, p = 0.001). At the end of the study period (48 weeks), total cholesterol (3.89 ± 0.92 vs. 4.52 ± 1.14 mmol/L, p = 0.012), low density lipoprotein cholesterol (2.24 ± 0.74 vs. 2.63 ± 0.82 mmol/L, p = 0.045) and triglyceride (1.35 (0.86) vs. 1.89 (1.27) mmol/l, p = 0.013) in roxadustat group were significantly lower than those in EPO group. CONCLUSIONS Roxadustat not only can improve anemia and iron metabolism, but also can reduce serum cholesterol and triglyceride levels in PD patients after switching from the EPO.
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Affiliation(s)
- Tian Xu
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yilin Ruan
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Na Liu
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yi Wang
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiujuan Zang
- Department of Nephrology, Shanghai Songjiang District Central Hospital, Shanghai, China
| | - Yuhua Ma
- Department of Nephrology, Traditional Chinese Medicine Hospital of Kunshan, Kunshan, Jiangsu, China
| | - Hualin Qi
- Department of Nephrology, The People’s Hospital of Pudong New District in Shanghai, Shanghai, China
| | - Xiuhua Mi
- Department of Nephrology, Shanghai Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
| | - Geping Yu
- Department of Nephrology, Tonglu First People’s Hospital, Tonglu, Hangzhou, China
| | - Chunyan Zhang
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaomin Huang
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingyuan Xie
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Nan Chen
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Ren
- Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Tramontano D, Bini S, Maiorca C, Di Costanzo A, Carosi M, Castellese J, Arizaj I, Commodari D, Covino S, Sansone G, Minicocci I, Arca M, D'Erasmo L. Renal Safety Assessment of Lipid-Lowering Drugs: Between Old Certainties and New Questions. Drugs 2025; 85:755-775. [PMID: 40106181 DOI: 10.1007/s40265-025-02158-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2025] [Indexed: 03/22/2025]
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Quantitative and qualitative changes in plasma lipoprotein profiles are frequently associated with CKD and represent a significant risk factor for CVD in patients with CKD. Guidelines from the European Society of Cardiology and the European Atherosclerosis Society classify CKD as a condition with high or very high cardiovascular risk and set specific low-density lipoprotein cholesterol targets. Conventional lipid-lowering therapies (LLTs), such as statins, ezetimibe, and fibrates, can control CKD-associated dyslipidemia and, to some extent, prevent major atherosclerotic events in patients with CKD, but their use in clinical practice presents challenges because of the potential renal safety concerns. In recent years, novel therapies with the ability to lower both low-density lipoprotein cholesterol and triglycerides have been introduced to the market (e.g., proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, lomitapide, volanesorsen) to improve our ability to control lipid abnormalities. However, their impact on kidney functionality has not been fully elucidated. The aim of this review was to examine the renal safety profiles of various LLTs, with special reference to novel medications, and to highlight important considerations and guidance for the use of these medications in overt CKD or in patients with some degree of renal function impairment. We underscore the lack of a comprehensive understanding of kidney safety, particularly for novel LLT therapies, and strongly emphasize the importance of future dedicated research to fully assess the safety and efficacy of these agents in patients with kidney abnormalities.
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Affiliation(s)
- Daniele Tramontano
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
| | - Simone Bini
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Carlo Maiorca
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Alessia Di Costanzo
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Martina Carosi
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Jacopo Castellese
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Ina Arizaj
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Daniela Commodari
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Stella Covino
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Giorgia Sansone
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Ilenia Minicocci
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Marcello Arca
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Laura D'Erasmo
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
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Shroff GR, Duprez DA, Manning E, Choi Y, Kramer HJ, Chang AR, Jacobs DR. Inflammatory and Cardiovascular Events in CKD: The Multi-Ethnic Study of Atherosclerosis. Am J Kidney Dis 2025:S0272-6386(25)00861-3. [PMID: 40381932 DOI: 10.1053/j.ajkd.2025.03.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 03/13/2025] [Accepted: 03/17/2025] [Indexed: 05/20/2025]
Abstract
RATIONALE & OBJECTIVE Chronic kidney disease (CKD) is associated with a proinflammatory state caused by maladaptive immune response, predisposing to cardiovascular (CVD) and inflammatory/infectious disease outcomes. We sought to examine the association of chronic inflammation-related disease (ChrIRD) as compared to CVD events with worsening kidney function. STUDY DESIGN Longitudinal, observational study over 19 years follow-up. SETTING & PARTICIPANTS Participants free of CVD were enrolled from the Multi-Ethnic Study of Atherosclerosis (MESA), a multicenter, population-based cohort. EXPOSURE Baseline 5-level CKD categories based on modified KDIGO (Kidney Disease Improving Global Outcomes) groups using estimated glomerular filtration rate (eGFR, mL/min/1.73m2) and UACR (urine albumin-creatinine ratio, mg/g). OUTCOME(S) 3 outcomes of interest: time to occurrence of first ChrIRD, time to first CVD, and time to all-cause mortality. ChrIRD encompassed inflammatory or infectious conditions identified using ICD (except kidney codes). ANALYTICAL APPROACH Proportional hazards regression analysis RESULTS: 6,705 participants (mean age 62 years, 53% female, 38.5% White, 27.6% Black, 22% Hispanic, 11.9% Chinese) were studied. Among study participants, 70% had no CKD, 17% low-risk CKD (eGFR>60 + UACR<10-29); 7% moderate-risk CKD (eGFR ≥60 + UACR 30-299), 4.6% high-risk CKD (eGFR 30-59 + UACR <30 or eGFR 45-59 + UACR 30-299 or eGFR ≥60 and UACR ≥300), 0.8% very high-risk (more advanced combinations of eGFR/UACR). Over 19-years follow-up, unadjusted incidence density (events/1000-person-years) of ChrIRD, CVD events were (respectively): 18, 11.9 for no CKD, 26.3, 18.4 low-risk, 39.7, 29.6 moderate-risk, 60.1, 35.4 high-risk CKD and 128.7, 56.6 very high-risk categories. After demographic adjustment, respective HRs (95% CI) for ChrIRD and CVD events were 1.23 (1.10-1.39), 1.35 (1.17-1.55) for low-risk, generally increasing to 3.87 (2.75-5.44), 2.84 (1.85-4.36) for very high-risk CKD categories. LIMITATIONS Unmeasured confounders and selection bias. CONCLUSIONS ChrIRD increased in a graded fashion with worsening CKD risk categories, starting with UACR > 10 mg/g.
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Affiliation(s)
- Gautam R Shroff
- Division of Cardiology and Department of Medicine, Hennepin Healthcare, Minneapolis, MN; University of Minnesota Medical School, Minneapolis, MN.
| | - Daniel A Duprez
- Division of Cardiology, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN
| | - Evan Manning
- Division of Cardiology, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN
| | - Yuni Choi
- Department of Medicine, Division of General Medicine, Columbia University Irving Medical Center, New York, NY
| | - Holly J Kramer
- Department of Public Health Sciences, Loyola University Chicago Stritch School of Medicine, Maywood, IL; Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, IL; Hines VA Medical Center, Hines, IL
| | - Alexander R Chang
- Department of Population of Health Sciences, Geisinger, Danville, PA; Center for Kidney Health Research, Geisinger, Danville, PA; Department of Nephrology, Geisinger, Danville, PA
| | - David R Jacobs
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
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5
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Cheng FWT, Xu W, Tang SCW, Wan EYF. Long-Term Benefits and Safety of Statins in Patients with Kidney Failure: A Target Trial Emulation Study. J Am Soc Nephrol 2025; 36:882-889. [PMID: 39480503 PMCID: PMC12059101 DOI: 10.1681/asn.0000000554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 10/28/2024] [Indexed: 11/02/2024] Open
Abstract
Key Points Patients with kidney failure are at a higher risk of cardiovascular diseases, but the evidence for statin therapy remains inconclusive. The long-term benefits and risks of statin therapy in patients with kidney failure were analyzed using public electronic health records in Hong Kong. Statin therapy was associated with a lower risk of major cardiovascular diseases and all-cause mortality without a higher risk of major adverse events. Background Patients with kidney failure are at elevated risk of cardiovascular diseases. Although statins are commonly used to mitigate cardiovascular risk among the population with high risk, the evidence for initiating statin therapy among patients with kidney failure remains inconclusive. This study aimed to investigate the long-term benefits and risks associated with statin therapy in patients with kidney failure. Methods Using territory-wide public electronic health records in Hong Kong, 3019 statin-eligible individuals with kidney failure and elevated LDL cholesterol ≥100 mg/dl from January 2008 to December 2015 were included for analysis. The framework of target trial emulation was adopted to investigate the risk of the major cardiovascular diseases (i.e ., a composite of myocardial infarction, heart failure, and stroke), all-cause mortality, and major adverse events (i.e ., myopathies and liver dysfunction) between statin initiators and statin noninitiators. The pooled logistic model was used to obtain the hazard ratio for the outcomes of interest in both intention-to-treat (ITT) analysis and per-protocol (PP) analysis. Results Significant risk reduction associated with statin therapy (hazard ratio [95% confidence interval]) was observed for major cardiovascular diseases (ITT: 0.78 [0.62 to 0.98]; PP: 0.66 [0.50 to 0.87]) and all-cause mortality (ITT: 0.80 [0.68 to 0.95]; PP: 0.60 [0.48 to 0.76]). The standardized 5- and 10-year absolute risk reduction in PP analysis was 7% (3% to 11%) and 11% (4% to 18%), respectively. No significant risks for the major adverse events were observed. Conclusions Statin therapy was associated with lower risks of cardiovascular diseases and all-cause mortality in patients with kidney failure without a higher risk of major adverse events.
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Affiliation(s)
- Franco Wing Tak Cheng
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Pharmacy Department, Gleneagles Hong Kong Hospital, Hong Kong SAR, China
| | - Wanchun Xu
- Department of Family Medicine and Primary Care, LKS Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Sydney Chi Wai Tang
- Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Eric Yuk Fai Wan
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Family Medicine and Primary Care, LKS Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health (D4H), Hong Kong Science and Technology Park, Hong Kong SAR, China
- The Institute of Cardiovascular Science and Medicine (ICSM), Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
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6
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Zhu D, Judge PK, Wanner C, Haynes R, Herrington WG. The prevention and management of chronic kidney disease among patients with metabolic syndrome. Kidney Int 2025; 107:816-824. [PMID: 39986466 DOI: 10.1016/j.kint.2024.12.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 12/02/2024] [Accepted: 12/20/2024] [Indexed: 02/24/2025]
Abstract
Treatment of patients with chronic kidney disease (CKD) requires implementation of prevention and management strategies that reduce the risk of kidney failure and CKD-associated cardiovascular risk. Metabolic syndrome is characterized by obesity, high blood pressure, dyslipidemia, and hyperglycemia, and it is common among patients with CKD. Large-scale randomized trials have led to significant advances in the management of CKD, with 5 pharmacotherapies now proven to be nephroprotective and/or cardioprotective in certain types of patients. Renin-angiotensin system inhibitors and sodium-glucose cotransporter 2 inhibitors slow kidney disease progression and reduce heart failure complications for most patients with CKD. In addition, statin-based regimens reduce low-density lipoprotein cholesterol and lower the risk of atherosclerotic disease (with no clinically meaningful effect on kidney outcomes). For patients with type 2 diabetes and albuminuric CKD, the nonsteroidal mineralocorticoid receptor antagonist finerenone and the glucagon-like peptide-1 receptor agonist semaglutide also confer cardiorenal benefits, with semaglutide additionally effective at reducing weight. Together, these randomized data strongly suggest that metabolic syndrome mediates some of the cardiorenal risk observed in CKD. Considered separately, the trials help elucidate which components of metabolic syndrome influence the pathophysiology of kidney disease progression and which separately modify risk of atherosclerotic and nonatherosclerotic cardiovascular outcomes. As we predict complementary and different mechanisms of nephroprotection and cardioprotection for these different interventions, it seems logical that they should be deployed together to maximize benefits. Even when combined, however, these therapies are not a cure, so further trials remain important to reduce the residual cardiorenal risks associated with CKD.
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Affiliation(s)
- Doreen Zhu
- Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
| | - Parminder K Judge
- Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Christoph Wanner
- Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Richard Haynes
- Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - William G Herrington
- Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
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7
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Blum MF, Neuen BL, Grams ME. Risk-directed management of chronic kidney disease. Nat Rev Nephrol 2025; 21:287-298. [PMID: 39885336 DOI: 10.1038/s41581-025-00931-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2025] [Indexed: 02/01/2025]
Abstract
The timely and rational institution of therapy is a key step towards reducing the global burden of chronic kidney disease (CKD). CKD is a heterogeneous entity with varied aetiologies and diverse trajectories, which include risk of kidney failure but also cardiovascular events and death. Developments in the past decade include substantial progress in CKD risk prediction, driven in part by the accumulation of electronic health records data. In addition, large randomized clinical trials have demonstrated the effectiveness of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists in reducing adverse events in CKD, greatly expanding the options for effective therapy. Alongside angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, these classes of medication have been proposed to be the four pillars of CKD pharmacotherapy. However, all of these drug classes are underutilized, even in individuals at high risk. Leveraging prognostic estimates to guide therapy could help clinicians to prescribe CKD-related therapies to those who are most likely to benefit from their use. Risk-based CKD management thus aligns patient risk and care, allowing the prioritization of absolute benefit in determining therapeutic selection and timing. Here, we discuss CKD prognosis tools, evidence-based management and prognosis-guided therapies.
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Affiliation(s)
- Matthew F Blum
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Brendon L Neuen
- The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Morgan E Grams
- New York University Grossman School of Medicine, New York, NY, USA.
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8
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Safarova MS, Weintraub S, Sadaniantz K, Kovell L, Warden BA, Garshick MS, Duell PB, Gianos E. Statin Use in Special Populations for the Prevention of Cardiovascular Disease in Adults. Curr Atheroscler Rep 2025; 27:54. [PMID: 40310600 DOI: 10.1007/s11883-025-01298-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2025] [Indexed: 05/02/2025]
Abstract
PURPOSE OF REVIEW Outcome benefits for HMG-CoA reductase inhibitor (statin) use in the prevention of atherosclerotic cardiovascular disease (ASCVD) are well established and yet, statins remain underutilized with only half of eligible individuals receiving them among certain vulnerable populations. This review critically examines available data to provide a summary of the current evidence for statin use in select populations. RECENT FINDINGS Lipid management can be more complex in patients with chronic kidney disease (CKD), organ transplants, metabolic dysfunction associated with steatotic liver disease (MASLD), and human immunodeficiency virus (HIV). Statins are generally safe and effective to reduce the burden of ASCVD among these highly heterogeneous groups of patients and should be considered with careful attention to their concomitant disease state. Herein, we focus on appropriate statin use in these challenging to treat conditions, their relationship with increased ASCVD risk, and approaches to statin use for ASCVD risk reduction. Although further research is needed to define optimal therapy in select high risk groups for ASCVD prevention, statins are proven to be clinically efficacious, safe, and cost-effective for ASCVD prevention, warranting greater efforts to increase their use.
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Affiliation(s)
- Maya S Safarova
- Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
| | - Spencer Weintraub
- Northwell Cardiovascular Institute, North Shore University Hospital, Manhasset, NY, USA
| | - Katherine Sadaniantz
- Department of Medicine, Division of Cardiovascular Medicine, UMass Chan Medical School, Worcester, MA, USA
| | - Lara Kovell
- Department of Medicine, Division of Cardiovascular Medicine, UMass Chan Medical School, Worcester, MA, USA
| | - Bruce A Warden
- Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA
| | - Michael S Garshick
- Division of Cardiology, Department of Medicine and Department of Dermatology, NYU Langone Health, New York, NY, USA
| | - P Barton Duell
- Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA
- Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health & Science University, Portland, OR, USA
| | - Eugenia Gianos
- Northwell Cardiovascular Institute, Lenox Hill Hospital, New York, NY, USA
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Zhang S, Lin H, Wang J, Rui J, Wang T, Cai Z, Huang S, Gao Y, Ma T, Fan R, Dai R, Li Z, Jia Y, Chen Q, He H, Tan J, Zhu S, Gu R, Dong Z, Li M, Xie E, Fu Y, Zheng J, Jiang C, Sun J, Kong W. Sensing ceramides by CYSLTR2 and P2RY6 to aggravate atherosclerosis. Nature 2025; 641:476-485. [PMID: 40049228 DOI: 10.1038/s41586-025-08792-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 02/14/2025] [Indexed: 04/18/2025]
Abstract
Recent evidence has shown that increased levels of circulating long-chain ceramides predict atherosclerotic cardiovascular disease independently of cholesterol1,2. Although targeting ceramide signalling may provide therapeutic benefits beyond the treatment of hypercholesterolaemia, the underlying mechanism by which circulating ceramides aggravate atherosclerotic cardiovascular disease remains elusive. Here we examine whether circulating long-chain ceramides activate membrane G-protein-coupled receptors to exacerbate atherosclerosis. We perform a systematic screen that combines G-protein-signalling quantification, bioinformatic analysis of G-protein-coupled receptor expression and functional examination of NLRP3 inflammasome activation. The results suggest that CYSLTR2 and P2RY6 are potential endogenous receptors of C16:0 ceramide-induced inflammasome activation in both endothelial cells and macrophages. Inhibition of CYSLTR2 and P2RY6 genetically or pharmacologically alleviates ceramide-induced atherosclerosis aggravation. Moreover, increased ceramide levels correlate with the severity of coronary artery disease in patients with varying degrees of renal impairment. Notably, CYSLTR2 and P2RY6 deficiency mitigates chronic-kidney-disease-aggravated atherosclerosis in mice without affecting cholesterol or ceramide levels. Structural analyses of ceramide-CYSLTR2-Gq complexes reveal that both C16:0 and C20:0 ceramides bind in an inclined channel-like ligand-binding pocket on CYSLTR2. We further reveal an unconventional mechanism underlying ceramide-induced CYSLTR2 activation and the CYSLTR2-Gq interface. Overall, our study provides structural and molecular mechanisms of how long-chain ceramides initiate transmembrane Gq and inflammasome signalling through direct binding to CYSLTR2 and P2RY6 receptors. Therefore, blocking these signals may provide a new therapeutic potential to treat atherosclerosis-related diseases.
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MESH Headings
- Animals
- Atherosclerosis/metabolism
- Atherosclerosis/pathology
- Humans
- Mice
- Ceramides/metabolism
- Ceramides/blood
- Ceramides/chemistry
- Male
- Inflammasomes/metabolism
- Receptors, Leukotriene/metabolism
- Receptors, Leukotriene/chemistry
- Receptors, Leukotriene/genetics
- Receptors, Leukotriene/deficiency
- Receptors, Purinergic P2/metabolism
- Receptors, Purinergic P2/chemistry
- Receptors, Purinergic P2/genetics
- Receptors, Purinergic P2/deficiency
- Female
- NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
- Coronary Artery Disease/pathology
- Coronary Artery Disease/metabolism
- Macrophages/metabolism
- Renal Insufficiency, Chronic/complications
- Renal Insufficiency, Chronic/metabolism
- Renal Insufficiency, Chronic/pathology
- Signal Transduction
- Mice, Inbred C57BL
- Models, Molecular
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Affiliation(s)
- Siting Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Hui Lin
- New Cornerstone Science Laboratory, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China
- Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
| | - Jiale Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
- Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
| | - Jingyu Rui
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
| | - Tengwei Wang
- New Cornerstone Science Laboratory, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China
- School of Pharmacy, Binzhou Medical University, Yantai, China
| | - Zeyu Cai
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Shenming Huang
- New Cornerstone Science Laboratory, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, China
| | - Yanxiang Gao
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Tianfeng Ma
- Department of Vascular and Endovascular Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Rui Fan
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
- Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
| | - Rongbo Dai
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Zhiqing Li
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Yiting Jia
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
- Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
| | - Qiang Chen
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - HaoMing He
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Jiaai Tan
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Shirong Zhu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Rui Gu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Zhigang Dong
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Meihong Li
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Enmin Xie
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Yi Fu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China
| | - Jingang Zheng
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.
| | - Changtao Jiang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China.
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China.
| | - Jinpeng Sun
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China.
- New Cornerstone Science Laboratory, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
- Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China.
- NHC Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Shandong, China.
| | - Wei Kong
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, P. R. China.
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China.
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10
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Ambalavanan J, Caramori ML. Management of Diabetes in Patients with Chronic Kidney Disease. Endocr Res 2025; 50:65-75. [PMID: 40119502 DOI: 10.1080/07435800.2025.2473896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 02/20/2025] [Accepted: 02/25/2025] [Indexed: 03/24/2025]
Abstract
BACKGROUND Patients with diabetes and chronic kidney disease (CKD) are at increased risk of kidney disease progression and cardiovascular events. METHODS In this article, we will summarize the 2022 consensus report by the ADA and KDIGO on diabetes management in CKD and include newly available evidence to assist health care professionals in providing optimal care to patients living with diabetes and CKD. RESULTS Comprehensive care strategies include lifestyle interventions, optimal glycemic, blood pressure, weight, and lipid management, and preferential use of therapies with proven heart and kidney beneficial effects. CONCLUSIONS This article offers a concise overview of the multiple strategies aimed at reducing cardiovascular and kidney risk among people with diabetes and CKD, as recommended by multiple societies.
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Affiliation(s)
- Jayachidambaram Ambalavanan
- Department of Endocrinology and Metabolism, Institute of Clinical Sciences, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Maria Luiza Caramori
- Department of Endocrinology and Metabolism, Institute of Clinical Sciences, Cleveland Clinic Foundation, Cleveland, Ohio, USA
- Department of Medicine, University of Minnesota, Minneapolis, MN, USA
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11
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McIntyre CW, Jain A. Dialysis and cognitive impairment. Nat Rev Nephrol 2025:10.1038/s41581-025-00960-3. [PMID: 40275017 DOI: 10.1038/s41581-025-00960-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/25/2025] [Indexed: 04/26/2025]
Abstract
People with chronic kidney disease who require maintenance dialysis characteristically experience accelerated and aggravated cognitive decline compared with those with advanced kidney disease who are not receiving this form of kidney replacement therapy. This effect is inadequately appreciated, but of crucial importance to patients, their carers and the health-care systems that support them. Although many of the comorbid conditions prevalent in this patient population have the potential to affect brain structure and function, an evolving body of evidence indicates that the dialysis therapy itself has a central role in the pathophysiology of progressive cognitive impairment. Both haemodialysis and peritoneal dialysis are associated with structural and functional changes in the brain that can lead to characteristic short-term symptoms, such as headache, confusion, delirium and brain fog, as well as long-term reductions in cognitive functional ability. Here, we explore the mechanisms, both established and putative, underlying these effects and consider approaches to addressing this issue with both single and complex therapeutic interventions.
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Affiliation(s)
- Chris W McIntyre
- Lilibeth Caberto Kidney Clinical Research Unit, Lawson Health Research Institute, London, Ontario, Canada.
- Departments of Medicine, Medical Biophysics and Paediatrics, Western University, London, Ontario, Canada.
| | - Arsh Jain
- Lilibeth Caberto Kidney Clinical Research Unit, Lawson Health Research Institute, London, Ontario, Canada
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12
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Meng J, Li W, Fu W, Zhang A. Baseline comorbidity of cardiovascular-kidney-metabolic syndrome increases the risk of adverse clinical outcomes in patients with chronic kidney disease. Front Endocrinol (Lausanne) 2025; 16:1563164. [PMID: 40309442 PMCID: PMC12040642 DOI: 10.3389/fendo.2025.1563164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Accepted: 03/31/2025] [Indexed: 05/02/2025] Open
Abstract
Introduction Our study aims to analyze the relationship between different stage of Cardiovascular-Kidney-Metabolic (CKM) Syndrome in Chronic Kidney Disease (CKD) patients and the risk of progression to all-caused mortality or end-stage renal disease (ESRD). Methods and results A retrospective cohort study was performed by collecting baseline data of CKD patients. All participants were followed throughout the course of the study. Cox proportional hazards analysis and Fine-Gray subdistribution model was performed to analyze the prognostic value of different CKM stages on the risk of adverse clinical outcomes (all-caused mortality or progression to ESRD) of these patients. 1,358 patients finally completed the follow-up. Among them, 1,233 patients were alive, and 125 patients had died; and 163 patients progressed to ESRD. Baseline CKM stage 3 (OR=3.906, 95% CI=0.988-16.320, p=0.048) and stage 4 (OR=5.728, 95% CI=1.329-24.698, p=0.019) remain independent risk factors for all-cause mortality in CKD patients, while CKM stage 2b (OR=2.739, 95% CI=1.157-6.486, p=0.022) were identified as having an independent risk factor for progression to ESRD in CKD patients by adjusting confounding factors. Conclusion Our research demonstrated that a high-risk CKM stage can predict adverse clinical outcomes in CKD patients, including all-cause mortality and progression to ESRD.
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Affiliation(s)
- Jiali Meng
- Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Wen Li
- Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Wenjing Fu
- Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Aihua Zhang
- Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China
- The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China
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13
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Rodríguez-Espinosa D, Cuadrado-Payán E, Morantes L, Gomez M, Maduell F, Broseta JJ. Lipid and immunophenotypic profiles in hemodialysis patients with citrate vs. acetate dialysates. Front Cardiovasc Med 2025; 12:1497353. [PMID: 40276257 PMCID: PMC12018436 DOI: 10.3389/fcvm.2025.1497353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 03/18/2025] [Indexed: 04/26/2025] Open
Abstract
Background Chronic kidney disease (CKD) is a significant cardiovascular (CV) risk factor, with dialysis-dependent CKD (DD-CKD) patients facing high mortality rates. Hypercholesterolemia is another crucial CV risk factor, typically managed with lipid-lowering therapy, though its efficacy in DD-CKD remains uncertain. Evidence shows mixed results regarding the benefits of statins in these patients. Citrate-based dialysates are known to reduce inflammatory biomarkers compared to acetate-based ones, potentially impacting lipid profiles and immune responses. This study aimed to determine the effects of citrate vs. acetate dialysate on lipid profiles and immunophenotypes in DD-CKD patients. Methods This unicentric, cross-over, prospective study included 21 hemodialysis patients (10 males, 11 females, average age 62.25 years). Each patient underwent 24 dialysis sessions (12 with each dialysate) and acted as their own control. Lipid profiles, immunological parameters, and nutritional and inflammatory markers were measured before the last session with each dialysate. Results After twelve dialysis sessions with citrate dialysate (CD), compared to acetate dialysate (AD), there was a statistically significant decline in TG and remnant cholesterol, with a decrease in HDL and an increase in LDL. Regarding immunology, C3 complement levels were higher, while CD3+ CD8+ and CD16+ 56+ lymphocytes were lower. Finally, total lymphocytes were lower with AD than with CD. We found no difference in predialysis nutritional nor inflammatory parameters except for ESR, which was higher when subjects used CD than AD. Conclusion There are significant differences in lipid and immunophenotypic profiles with CD in comparison to AD. Interestingly, there could be an advantageous profile given the reduced amount of remnant cholesterol and TG. However, further studies are needed to understand if the observed changes lead to beneficial hard clinical outcomes in DD-CKD patients.
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Affiliation(s)
| | | | | | | | | | - José Jesús Broseta
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
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14
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Marx-Schütt K, Cherney DZI, Jankowski J, Matsushita K, Nardone M, Marx N. Cardiovascular disease in chronic kidney disease. Eur Heart J 2025:ehaf167. [PMID: 40196891 DOI: 10.1093/eurheartj/ehaf167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 01/07/2025] [Accepted: 03/05/2025] [Indexed: 04/09/2025] Open
Abstract
Individuals with chronic kidney disease (CKD) exhibit an increased risk for the development of cardiovascular disease (CVD) with its manifestations coronary artery disease, stroke, heart failure, arrhythmias, and sudden cardiac death. The presence of both, CVD and CKD has a major impact on the prognosis of patients. This association likely reflects the involvement of several pathophysiological mechanisms, including shared risk factors (e.g. diabetes and hypertension), as well as other factors such as inflammation, anaemia, volume overload, and the presence of uraemic toxins. Identifying and characterizing CKD is crucial for appropriate CVD risk prediction. Mitigating CVD risk in patients with CKD mandates a multidisciplinary approach involving cardiologists, nephrologists, and other health care professionals. The present State-of-the-Art Review addresses the current understanding on the pathophysiological link between CVD and CKD, clinical implications and challenges in the treatment of these patients.
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Affiliation(s)
- Katharina Marx-Schütt
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen, Pauwelsstraße 30, Aachen D-52074, Aachen, Germany
| | - David Z I Cherney
- Department of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Joachim Jankowski
- Institute for Molecular Cardiovascular Research, University Hospital, RWTH Aachen, Pauwelsstraße 30, Aachen 52074, Germany
| | - Kunihiro Matsushita
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Massimo Nardone
- Department of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Nikolaus Marx
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen, Pauwelsstraße 30, Aachen D-52074, Aachen, Germany
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15
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Kelly DM, Kelleher EM, Rothwell PM. The Kidney-Immune-Brain Axis: The Role of Inflammation in the Pathogenesis and Treatment of Stroke in Chronic Kidney Disease. Stroke 2025; 56:1069-1081. [PMID: 39851054 PMCID: PMC11932449 DOI: 10.1161/strokeaha.124.047070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2025]
Abstract
Cardiovascular diseases such as stroke are a major cause of morbidity and mortality for patients with chronic kidney disease (CKD). The underlying mechanisms connecting CKD and cardiovascular disease are yet to be fully elucidated, but inflammation is proposed to play an important role based on genetic association studies, studies of inflammatory biomarkers, and clinical trials of anti-inflammatory drug targets. There are multiple sources of both endogenous and exogenous inflammation in CKD, including increased production and decreased clearance of proinflammatory cytokines, oxidative stress, metabolic acidosis, chronic and recurrent infections, dialysis access, changes in adipose tissue metabolism, and disruptions in intestinal microbiota. This review focuses on the mechanisms of inflammation in CKD, dialysis and associated therapies, its proposed impact on stroke pathogenesis and prognosis, and the potential role of anti-inflammatory agents in the prevention and treatment of stroke in patients with CKD.
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Affiliation(s)
- Dearbhla M. Kelly
- Wolfson Centre for the Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences (D.M.K., P.M.R.)
| | - Eoin M. Kelleher
- Nuffield Department of Clinical Neurosciences (E.M.K.), University of Oxford, United Kingdom
| | - Peter M. Rothwell
- Wolfson Centre for the Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences (D.M.K., P.M.R.)
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16
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Eriksson M. The combination of statin and ezetimibe is safe, effective, and preferable. J Intern Med 2025; 297:350-351. [PMID: 39988454 DOI: 10.1111/joim.20070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Affiliation(s)
- Mats Eriksson
- Deptartment of Medicine at Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
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17
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Ghimire A, Wanner C, Tonelli M. Closing CKD Treatment Gaps: Why Practice Guidelines and Better Drug Coverage Are Not Enough. Am J Kidney Dis 2025; 85:406-408. [PMID: 39945704 DOI: 10.1053/j.ajkd.2025.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 01/27/2025] [Accepted: 01/30/2025] [Indexed: 03/24/2025]
Affiliation(s)
- Anukul Ghimire
- Division of Nephrology, University of Calgary, Calgary, Canada
| | - Christoph Wanner
- Division of Nephrology, University of Würzburg, Würzburg, Germany
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18
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Cinza-Sanjurjo S, Pallarés-Carratalá V, Díaz Rodríguez A, Fierro-González D, Turégano-Yedro M, Polo-García J. [Practical approach to the patient with hypercholesterolemia in Spain. SEMERGEN position statement]. Semergen 2025; 51:102460. [PMID: 40139108 DOI: 10.1016/j.semerg.2025.102460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 01/15/2025] [Accepted: 01/22/2025] [Indexed: 03/29/2025]
Abstract
Hypercholesterolemia, specifically the increase in the set of lipoproteins containing apolipoproteinB and, in particular, low-density lipoprotein cholesterol (LDL-C), together with the decrease in high-density lipoprotein cholesterol (HDL-C) constitute the etiopathogenic basis of atherosclerotic vascular disease. Multiple clinical trials have shown that lowering LDL-C by lipid-lowering therapy is associated with a significant decrease in the risk of vascular complications. Thus, LDL-C is the main therapeutic target in patients with dyslipidemia. Unfortunately, current LDL-C control figures are still very low, partly due to insufficient intensification of lipid-lowering therapy, but also due to the need for new tools to achieve these goals. This paper reviews the different lipid-lowering treatment options, including the latest available therapies, and provides a practical approach to achieving LDL-C control goals in patients with hypercholesterolemia, as well as in different patient subgroups.
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Affiliation(s)
- S Cinza-Sanjurjo
- Centro de Salud Milladoiro, Área Sanitaria de Santiago de Compostela, Santiago de Compostela, A Coruña, España; Instituto de Investigación de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña, España; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, España; Grupo de Trabajo de Hipertensión Arterial y Enfermedad Cardiovascular de SEMERGEN; Agencia de Investigación de SEMERGEN; Junta directiva de SEMERGEN.
| | - V Pallarés-Carratalá
- Grupo de Trabajo de Hipertensión Arterial y Enfermedad Cardiovascular de SEMERGEN; Junta directiva de SEMERGEN; Departamento de Medicina, Universitat Jaume I, Castellón, España
| | - A Díaz Rodríguez
- Centro de Salud Bembibre, Bembibre, León, España; Grupo de Trabajo de Lípidos de SEMERGEN
| | - D Fierro-González
- Grupo de Trabajo de Lípidos de SEMERGEN; Centro de Salud de Armunia, León, España
| | - M Turégano-Yedro
- Grupo de Trabajo de Hipertensión Arterial y Enfermedad Cardiovascular de SEMERGEN; Centro de Salud Casar de Cáceres, Casar de Cáceres, Cáceres, España
| | - J Polo-García
- Grupo de Trabajo de Hipertensión Arterial y Enfermedad Cardiovascular de SEMERGEN; Junta directiva de SEMERGEN; Centro de Salud Casar de Cáceres, Casar de Cáceres, Cáceres, España
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19
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Theofilis P, Vlachakis PK, Karakasis P, Kalaitzidis RG. Managing Dyslipidemia in Chronic Kidney Disease: Implications for Cardiovascular and Renal Risk. Curr Atheroscler Rep 2025; 27:41. [PMID: 40117057 DOI: 10.1007/s11883-025-01290-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/10/2025] [Indexed: 03/23/2025]
Abstract
PURPOSE OF REVIEW The review aims to address the complex relationship between dyslipidemia and chronic kidney disease (CKD), emphasizing its dual role in driving cardiovascular disease (CVD) risk and contributing to CKD progression. It explores pathophysiological mechanisms, highlights recent biomarker discoveries, and evaluates contemporary and emerging lipid-lowering therapies tailored for CKD patients. RECENT FINDINGS Recent studies have highlighted the inadequacy of traditional lipid markers like LDL-C in reflecting cardiovascular risk in CKD. Novel biomarkers, such as remnant cholesterol and lipoprotein(a), demonstrate stronger associations with adverse outcomes. Emerging lipid-lowering agents, including bempedoic acid, pemafibrate, and PCSK9 inhibitors, show promise for risk reduction, especially in non-dialysis-dependent CKD. However, evidence remains limited for advanced stages of CKD and dialysis patients. Furthermore, alterations in lipid metabolism, such as dysfunctional HDL and triglyceride-rich lipoproteins, are now recognized as significant contributors to CVD and renal damage in CKD populations. Dyslipidemia is a pivotal modifiable risk factor in CKD, exacerbating both cardiovascular risk and disease progression. While statins remain the cornerstone of therapy in early-to-moderate CKD, their efficacy diminishes in advanced stages. The advent of novel therapeutic options and a deeper understanding of dyslipidemia's pathophysiology hold potential for improving outcomes. Future research should prioritize personalized approaches, focusing on the unique metabolic derangements of CKD and advancing treatments for high-risk and dialysis-dependent patients.
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Affiliation(s)
- Panagiotis Theofilis
- Center for Nephrology "G. Papadakis", General Hospital of Nikaia-Piraeus Agios Panteleimon, 18454, Piraeus, Greece
- First Department of Cardiology, "Hippokration" General Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece
| | - Panayotis K Vlachakis
- First Department of Cardiology, "Hippokration" General Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece
| | - Paschalis Karakasis
- Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642, Thessaloniki, Greece
| | - Rigas G Kalaitzidis
- Center for Nephrology "G. Papadakis", General Hospital of Nikaia-Piraeus Agios Panteleimon, 18454, Piraeus, Greece.
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20
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Hobbs FDR, McManus R, Taylor C, Jones N, Rahman J, Wolstenholme J, Jones L, Hirst J, Mort S, Yu LM. Benefits of aldosterone receptor antagonism in chronic kidney disease: the BARACK-D RCT. Health Technol Assess 2025; 29:1-130. [PMID: 40106397 PMCID: PMC11931407 DOI: 10.3310/pyft6977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025] Open
Abstract
Background Chronic kidney disease affects around 10% of the global population and is associated with significant risk of progression to end-stage renal disease and vascular events. Aldosterone receptor antagonists such as spironolactone have shown prognostic benefits in patients with heart failure, but effects on patients with chronic kidney disease are uncertain. Objectives To determine the effect of low-dose spironolactone on mortality and cardiovascular outcomes in people with chronic kidney disease stage 3b. Design Prospective randomised open blinded end-point trial. Settings Three hundred and twenty-nine general practitioner practices throughout the United Kingdom. Participants Patients meeting the criteria for chronic kidney disease stage 3b (estimated glomerular filtration rate 30-44 ml/minute/1.73 m2) according to National Institute for Health and Care Excellence guidelines were recruited. Due to the higher than anticipated measurement error/fluctuations, the eligible range was extended to 30-50 ml/minute/1.73 m2 following the initial recruitment period. Intervention Participants were randomised 1 : 1 to receive either spironolactone 25 mg once daily in addition to standard care, or standard care only. Outcome measures Primary outcome was the first occurring of all-cause mortality, first hospitalisation for heart disease (coronary heart disease, arrhythmia, atrial fibrillation, sudden death, failed sudden death), stroke, heart failure, transient ischaemic attack or peripheral arterial disease, or first occurrence of any condition not listed at baseline. Secondary outcome measures included changes in blood pressure, renal function, B-type natriuretic peptide, incidence of hyperkalaemia and treatment costs and benefits. Results One thousand four hundred and thirty-four participants were randomised of the 3022 planned. We found no evidence of differences between the intervention and control groups in terms of effectiveness with the primary combined vascular end points, nor with the secondary clinical outcomes, including progression in renal decline. These results were similar for the total treatment periods or a 3-year follow-up period as originally planned. More adverse events were experienced and more participants discontinued treatment in the intervention group. Two-thirds of participants randomised to spironolactone stopped treatment within six months because they met pre-specified safety stop criteria. The addition of low-dose spironolactone was estimated to have a cost per quality-adjusted life-year gained value above the National Institute for Health and Care Excellence's threshold of £30,000. Limitations Main limitations were difficulties in recruiting eligible participants resulting in an underpowered trial with poor ethnic diversity taking twice as long as planned to complete. We have explored the data in secondary analyses that indicate that, despite these difficulties, the findings were reliable. Conclusions The benefits of aldosterone receptor antagonism in chronic kidney disease trial found no evidence to support adding low-dose spironolactone (25 mg daily) in patients with chronic kidney disease stage 3b: there were no changes to cardiovascular events during the trial follow-up, either for the combined primary or individual components. There was also no evidence of benefit observed in rates of renal function decline over the trial, but much higher initial creatinine rise and estimated glomerular filtration rate decline, and to a higher percentage rate, in the intervention arm in the first few weeks of spironolactone treatment, which resulted in a high proportion of participants discontinuing spironolactone treatment at an early stage. These higher rates of negative renal change reduced in scale over the study but did not equalise between arms. The addition of 25 mg of spironolactone therefore provided no reno- or cardio-protection and was associated with an increase in adverse events. Future work These findings might not be applicable to different mineralocorticoid receptor antagonists. Study registration Current Controlled Trials ISRCTN44522369. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/01/52) and is published in full in Health Technology Assessment; Vol. 29, No. 5. See the NIHR Funding and Awards website for further award information.
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Affiliation(s)
- F D Richard Hobbs
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
- NIHR Applied Research Collaboration Oxford and Thames Valley, Oxford, UK
| | - Richard McManus
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
| | - Clare Taylor
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Nicholas Jones
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
| | - Joy Rahman
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
| | - Jane Wolstenholme
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Louise Jones
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
| | - Jennifer Hirst
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
| | - Sam Mort
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
| | - Ly-Mee Yu
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
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Tian D, Chen Q, Zeng L, Hao Y. The impact of blood lipids and statins on renal function and mortality in patients with diabetic nephropathy: A meta-analysis. ACTA PHARMACEUTICA (ZAGREB, CROATIA) 2025; 75:1-22. [PMID: 39686670 DOI: 10.2478/acph-2025-0002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/12/2024] [Indexed: 12/18/2024]
Abstract
The aim of this study is to explore the impact of blood lipids and statins on renal function and all-cause mortality in patients with diabetic nephropathy (DN). PubMed, Embase, Web of Science, and Cochrane Library were systematically searched until April 9, 2024, for relevant studies of blood lipids and statins on renal function and all-cause mortality in patients with DN. After the selection, total cholesterol levels (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), serum creati-nine (SCR), end-stage renal disease (ESRD), and all-cause mortality indexes were extracted for finally meta-analysis. In total, 25 papers containing 21,411 patients with DN were finally included in this study. Levels of TC and LDL-C, which are continuous variables, were higher in DN patients who developed ESRD [TC/weighted mean difference (WMD) = 0.517, 95 % confidence interval (CI): (0.223, 0.812), p = 0.001; LDL-C/WMD = 0.449, 95%CI: (0.200, 0.698), p < 0.001]. In addition, this study also observed that statins may reduce UAE levels [WMD = -46.814, 95% CI: (-71.767, -21.861), p < 0.001]. Finally, the survey indicated that statins may be associated with an ESRD reduction [HR = 0.884, 95% CI: (0.784, 0.998), p = 0.045]. Blood lipids, particularly TC and LDL-C, may slow the progression of DN to ESRD. Besides, statins may protect the kidneys by lowering the excretion of UAE levels and reducing the risk of ESRD. Based on the above outcomes, the findings of this study provided robust evidence-based medical support for the future prevention, surveillance, and management of DN.
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Affiliation(s)
- Dongqin Tian
- 1Department of Nephrology, Zigong First People's Hospital Zigong 643000, Sichuan P.R. China
| | - Qian Chen
- 1Department of Nephrology, Zigong First People's Hospital Zigong 643000, Sichuan P.R. China
| | - Lingli Zeng
- 1Department of Nephrology, Zigong First People's Hospital Zigong 643000, Sichuan P.R. China
| | - Yan Hao
- 1Department of Nephrology, Zigong First People's Hospital Zigong 643000, Sichuan P.R. China
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Mancini GBJ, Ryomoto A, Yeoh E, Iatan I, Brunham LR, Hegele RA. Reappraisal of statin primary prevention trials: implications for identification of the statin-eligible primary prevention patient. Eur J Prev Cardiol 2025:zwaf048. [PMID: 39998386 DOI: 10.1093/eurjpc/zwaf048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/14/2024] [Accepted: 01/28/2025] [Indexed: 02/26/2025]
Abstract
BACKGROUND AND AIMS Identification of patients eligible for primary prevention statin therapy is complex, often relying upon risk algorithms that diverge internationally. Our goal was to develop a simpler global definition of statin-eligible primary prevention patients. METHODS Randomized clinical trials (RCTs) cited in North American and European dyslipidemia guidelines justifying primary prevention statins for cardiovascular risk reduction were critically reappraised according to eligibility criteria and characteristics of actual enrollees. Statin-eligibility based on meeting minimal enrolment criteria versus risks calculated using either the Framingham Risk Score, the Pooled Cohort Equation and the Systematic Coronary Risk Estimate 2 were contrasted. RESULTS Patient scenarios meeting minimal RCT eligibility criteria seldom attained high enough 10 year risk of events according to the algorithms tested and thus would not be eligible for statin therapy. Overall, enrollees were 63.9 ± 8.9 years (mean ± SD) with low density lipoprotein-cholesterol (LDL-C) 3.53 ± 0.91 mmol/L. Enrollees in trials studying the lowest LDL-C levels were generally older and had additional risk factors. CONCLUSIONS Results of primary prevention RCTs justify treatment of more subjects and lower risk subjects than current risk algorithm-based guidelines. Based on a synthesis of RCT inclusion/exclusion criteria and the characteristics of enrollees, we propose that a statin-indicated primary prevention subject is one who is 40 to 70 years with a low density lipoprotein-cholesterol (LDL-C) ≥ 3.0 mmol/L or is 55 to 80 years with LDL-C ≥ 1.8 mmol/L and additional risk factors.
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Affiliation(s)
- G B John Mancini
- Department of Medicine, Division of Cardiology, Centre for Cardiovascular Innovation and Cardiovascular Imaging Research Core Laboratory (CIRCL), University of British Columbia, Vancouver, British Columbia, CANADA
| | - Arnold Ryomoto
- Department of Medicine, Division of Cardiology, Centre for Cardiovascular Innovation and Cardiovascular Imaging Research Core Laboratory (CIRCL), University of British Columbia, Vancouver, British Columbia, CANADA
| | - Eunice Yeoh
- Department of Medicine, Division of Cardiology, Centre for Cardiovascular Innovation and Cardiovascular Imaging Research Core Laboratory (CIRCL), University of British Columbia, Vancouver, British Columbia, CANADA
| | - Iulia Iatan
- Department of Medicine, Division of General Internal Medicine, Centre for Heart and Lung Innovation, University of British Columbia, Vancouver, British Columbia, CANADA
| | - Liam R Brunham
- Department of Medicine, Division of General Internal Medicine, Centre for Heart and Lung Innovation, University of British Columbia, Vancouver, British Columbia, CANADA
| | - Robert A Hegele
- Departments of Medicine and Biochemistry, Division of Endocrinology, Robarts Research Institute, University of Western Ontario, London, Ontario CANADA
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23
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Nicholls SJ, Nelson AJ. Achieving More Optimal Lipid Control with Non-Statin Lipid Lowering Therapy. Curr Atheroscler Rep 2025; 27:32. [PMID: 39954169 PMCID: PMC11829850 DOI: 10.1007/s11883-025-01280-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2025] [Indexed: 02/17/2025]
Abstract
PURPOSE OF REVIEW The use of statins has transformed approaches to the prevention of cardiovascular disease. However, many patients remain at a major risk of experiencing cardiovascular events, due to a range of factors including suboptimal control of low-density lipoprotein cholesterol (LDL-C). Accordingly, there is an ongoing need to develop additional strategies, beyond the use of statins, to achieve more effective reductions in cardiovascular risk. RECENT FINDINGS Genomic studies have implicated the causal role of LDL in atherosclerosis and identified that polymorphisms influencing factors involved in lipid metabolism influence both the level of LDL-C and cardiovascular risk. These findings have highlighted the potential for cardiovascular benefit from development of therapies targeting these factors and incremental benefit when used in combination with statins. Clinical trials have demonstrated that these new agents have favourable effects on both atherosclerotic plaque and cardiovascular events. Additional work has sought to improve intensification of statin therapy and adherence with lipid lowering therapy, to achieve more effective cardiovascular prevention via lipid lowering. Emerging therapies, beyond statins, have the potential to optimise lipid levels and play an effective role in the prevention of cardiovascular disease.
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Affiliation(s)
- Stephen J Nicholls
- Victorian Heart Institute, Monash University, 631 Blackburn Rd, Clayton, Melbourne, Australia.
| | - Adam J Nelson
- Victorian Heart Institute, Monash University, 631 Blackburn Rd, Clayton, Melbourne, Australia
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Yao Y, Xiong J, Wang MY. Dose-response relationship between lipids and all-cause mortality in the dialysis population: a meta-analysis. BMC Nephrol 2025; 26:55. [PMID: 39905322 PMCID: PMC11796159 DOI: 10.1186/s12882-025-03981-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 01/24/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND The use of lipid-lowering drugs in the dialysis population has been controversial and there is no target for the dialysis population. OBJECTIVES To elucidate the dose-response relationship between lipids and all-cause mortality in the dialysis population. METHODS Computer searches of PubMed, Embase, Web of Science, CNKI, and Wanfang. Data were conducted to collect published cohort studies on lipids and all-cause mortality in the dialysis population from home and abroad up to February 2023. Meta-analysis was applied to calculate the combined effect size (Hazard ratio) and its 95% confidence interval and dose-response relationship by applying Stata17.0. RESULTS A total of 11 publications with a cumulative total of 106,808 individuals were included. All-cause mortality was statistically different between the highest dose total cholesterol (TC) group and the low TC group (HR = 0.82, 95% CI = 0.75-0.90, P < 0.05). The TC range for lower all-cause mortality is > 140.5 mg/dL, and on this basis, TC in the range of 180-220 mg/dL may have a better prognosis for dialysis population. There was a nonlinear relationship between Non-high-density lipoprotein cholesterol (NHDL-C) cholesterol and all-cause mortality, with no statistical difference between the high and low dose group. In contrast, Low-density lipoprotein cholesterol (LDL-C) masked its association with all-cause mortality due to changes in death spectrum, differences in relative time risks, and other factors. In the 50-450 mg/dL range, all-cause mortality in the dialysis population was positively associated with triglycerides (TG), with a 2.5% increase in all-cause mortality per 50 mg/dL increase in TG (HR = 1.025, 95% CI = 1.003-1.048, P = 0.01). CONCLUSION TC is a target for monitoring the dialysis population, which has the lowest all-cause mortality in the range of 180-220 mg/dL. However, NHDL-C and LDL-C monitoring is not clinically meaningful. Increased TG can contribute to the risk of higher all-cause mortality in dialysis patients.
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Affiliation(s)
- Ye Yao
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jing Xiong
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Mi-Yuan Wang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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25
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Manski-Nankervis JA, Hunter B, Lumsden N, Laughlin A, McMorrow R, Boyle D, Chondros P, Jesudason S, Radford J, Prictor M, Emery J, Amores P, Tran-Duy A, Nelson C. Effectiveness of Electronic Quality Improvement Activities to Reduce Cardiovascular Disease Risk in People With Chronic Kidney Disease in General Practice: Cluster Randomized Trial With Active Control. JMIR Form Res 2025; 9:e54147. [PMID: 39899838 PMCID: PMC11833263 DOI: 10.2196/54147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 09/12/2024] [Accepted: 12/03/2024] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND Future Health Today (FHT) is a program integrated with electronic medical record (EMR) systems in general practice and comprises (1) a practice dashboard to identify people at risk of, or with, chronic disease who may benefit from intervention; (2) active clinical decision support (CDS) at the point of care; and (3) quality improvement activities. One module within FHT aims to facilitate cardiovascular disease (CVD) risk reduction in people with chronic kidney disease (CKD) through the recommendation of angiotensin-converting enzyme inhibitor inhibitors (ACEI), angiotensin receptor blockers (ARB), or statins according to Australian guidelines (defined as appropriate pharmacological therapy). OBJECTIVE This study aimed to determine if the FHT program increases the proportion of general practice patients with CKD receiving appropriate pharmacological therapy (statins alone, ACEI or ARB alone, or both) to reduce CVD risk at 12 months postrandomization compared with active control (primary outcome). METHODS General practices recruited through practice-based research networks in Victoria and Tasmania were randomly allocated 1:1 to the FHT CKD module or active control. The intervention was delivered to practices between October 4, 2021, and September 30, 2022. Data extracted from EMRs for eligible patients identified at baseline were used to evaluate the trial outcomes at the completion of the intervention period. The primary analysis used an intention-to-treat approach. The intervention effect for the primary outcome was estimated with a marginal logistic model using generalized estimating equations with robust SE. RESULTS Overall, of the 734 eligible patients from 19 intervention practices and 715 from 21 control practices, 82 (11.2%) and 70 (9.8%), respectively, had received appropriate pharmacological therapy (statins alone, ACEI or ARB alone, or both) at 12 months postintervention to reduce CVD risk, with an estimated between-trial group difference (Diff) of 2.0% (95% CI -1.6% to 5.7%) and odds ratio of 1.24 (95% CI 0.85 to 1.81; P=.26). Of the 470 intervention patients and 425 control patients that received a recommendation for statins, 61 (13%) and 38 (9%) were prescribed statins at follow-up (Diff 4.3%, 95% CI 0 to 8.6%; odds ratio 1.55, 95% CI 1.02 to 2.35; P=.04). There was no statistical evidence to support between-group differences in other secondary outcomes and general practice health care use. CONCLUSIONS FHT harnesses the data stored within EMRs to translate guidelines into practice through quality improvement activities and active clinical decision support. In this instance, it did not result in a difference in prescribing or clinical outcomes except for small changes in statin prescribing. This may relate to COVID-19-related disruptions, technical implementation challenges, and recruiting higher performing practices to the trial. A separate process evaluation will further explore factors impacting implementation and engagement with FHT. TRIAL REGISTRATION ACTRN12620000993998; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380119.
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Affiliation(s)
- Jo-Anne Manski-Nankervis
- Primary Care and Family Medicine, Lee Kong Chian School of Medicine, Singapore, Singapore
- Centre for Research Excellence in Interactive Digital Technology to Transform Australia's Chronic Disease Outcomes, Prahan, Australia
- Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia
| | - Barbara Hunter
- Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia
| | - Natalie Lumsden
- Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia
- Western Health Chronic Disease Alliance, Western Health, Sunshine, Australia
| | - Adrian Laughlin
- Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia
| | - Rita McMorrow
- Centre for Research Excellence in Interactive Digital Technology to Transform Australia's Chronic Disease Outcomes, Prahan, Australia
- Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia
- Department of General Practice, University College Cork, Cork, Ireland
| | - Douglas Boyle
- Centre for Research Excellence in Interactive Digital Technology to Transform Australia's Chronic Disease Outcomes, Prahan, Australia
- Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia
| | - Patty Chondros
- Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia
| | - Shilpanjali Jesudason
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia
| | - Jan Radford
- Launceston Clinical School, University of Tasmania, Launceston, Australia
| | - Megan Prictor
- Melbourne Law School, University of Melbourne, Melbourne, Australia
| | - Jon Emery
- Department of General Practice and Primary Care, University of Melbourne, Melbourne, Australia
| | - Paul Amores
- Centre for Health Policy, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
| | - An Tran-Duy
- Centre for Health Policy, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
- Australian Centre for Accelerating Diabetes, University of Melbourne, Melbourne, Australia
| | - Craig Nelson
- Western Health Chronic Disease Alliance, Western Health, Sunshine, Australia
- Department of Medicine, University of Melbourne, Sunshine, Australia
- Department of Nephrology, Western Health, Sunshine, Australia
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Rajesh K, Spring KJ, Smokovski I, Upmanyue V, Mehndiratta MM, Strippoli GFM, Beran RG, Bhaskar SMM. The impact of chronic kidney disease on prognosis in acute stroke: unraveling the pathophysiology and clinical complexity for optimal management. Clin Exp Nephrol 2025; 29:149-172. [PMID: 39627467 DOI: 10.1007/s10157-024-02556-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 08/25/2024] [Indexed: 01/03/2025]
Abstract
BACKGROUND Chronic kidney disease (CKD) significantly increases stroke risk and severity, posing challenges in both acute management and long-term outcomes. CKD contributes to cerebrovascular pathology through systemic inflammation, oxidative stress, endothelial dysfunction, vascular calcification, impaired cerebral autoregulation, and a prothrombotic state, all of which exacerbate stroke risk and outcomes. METHODS This review synthesizes evidence from peer-reviewed literature to elucidate the pathophysiological mechanisms linking CKD and stroke. It evaluates the efficacy and safety of acute reperfusion therapies-intravenous thrombolysis and endovascular thrombectomy-in CKD patients with acute ischemic stroke. Considerations, such as renal function, drug dosage adjustments, and the risk of contrast-induced nephropathy, are critically analyzed. Evidence-based recommendations and research priorities are drawn from an analysis of current practices and existing knowledge gaps. RESULTS CKD influences stroke outcomes through systemic and local pathophysiological changes, necessitating tailored therapeutic approaches. Reperfusion therapies are effective in CKD patients but require careful monitoring of renal function to mitigate risks, such as contrast-induced nephropathy and thrombolytic complications. The bidirectional relationship between stroke and CKD highlights the need for integrated management strategies to address both conditions. Early detection and optimized management of CKD significantly reduce stroke-related morbidity and mortality. CONCLUSION Optimizing stroke care in CKD patients requires a comprehensive understanding of their pathophysiology and clinical management challenges. This article provides evidence-based recommendations, emphasizing individualized treatment decisions and coordinated care. It underscores the importance of integrating renal considerations into stroke treatment protocols and highlights the need for future research to refine therapeutic strategies, address knowledge gaps, and consider tailored interventions to improve outcomes and quality of life for this high-risk population.
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Affiliation(s)
- Kruthajn Rajesh
- Global Health Neurology Lab, Sydney, NSW, 2150, Australia
- UNSW Medicine and Health, University of New South Wales (UNSW), South West Sydney Clinical Campuses, Sydney, NSW 2F170, Australia
| | - Kevin J Spring
- NSW Brain Clot Bank, NSW Health Pathology, Sydney, NSW, 2170, Australia
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Sydney, NSW, 2751, Australia
- School of Medicine, Western Sydney University, Sydney, NSW, 2000, Australia
| | - Ivica Smokovski
- Diabetes and Metabolic Disorders Skopje, Faculty of Medical Sciences, University Clinic of Endocrinology, The Goce Delčev University of Štip, Štip, North Macedonia
| | - Vedant Upmanyue
- Global Health Neurology Lab, Sydney, NSW, 2150, Australia
- UNSW Medicine and Health, University of New South Wales (UNSW), South West Sydney Clinical Campuses, Sydney, NSW 2F170, Australia
| | | | - Giovanni F M Strippoli
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia
- Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari "Aldo Moro", 70124, Bari, Italy
| | - Roy G Beran
- Global Health Neurology Lab, Sydney, NSW, 2150, Australia
- UNSW Medicine and Health, University of New South Wales (UNSW), South West Sydney Clinical Campuses, Sydney, NSW 2F170, Australia
- NSW Brain Clot Bank, NSW Health Pathology, Sydney, NSW, 2170, Australia
- School of Medicine, Western Sydney University, Sydney, NSW, 2000, Australia
- Griffith Health, School of Medicine and Dentistry, Griffith University, Southport, QLD, 4215, Australia
- Department of Neurology & Neurophysiology, Liverpool Hospital and South West Sydney Local Health District, Liverpool, NSW, 2170, Australia
| | - Sonu M M Bhaskar
- Global Health Neurology Lab, Sydney, NSW, 2150, Australia.
- UNSW Medicine and Health, University of New South Wales (UNSW), South West Sydney Clinical Campuses, Sydney, NSW 2F170, Australia.
- NSW Brain Clot Bank, NSW Health Pathology, Sydney, NSW, 2170, Australia.
- Department of Neurology & Neurophysiology, Liverpool Hospital and South West Sydney Local Health District, Liverpool, NSW, 2170, Australia.
- National Cerebral and Cardiovascular Center (NCVC), Department of Neurology, Division of Cerebrovascular Medicine and Neurology, Suita, Osaka, 564-8565, Japan.
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Mae Y, Takata T, Taniguchi S, Fujino Y, Kageyama K, Hanada H, Iyama T, Sugihara T, Isomoto H. Selective peroxisome proliferator-activated receptor-α modulator improves hypertriglyceridemia and muscle quality in patients with chronic kidney disease: A retrospective observational study. Clin Nutr ESPEN 2025; 65:182-188. [PMID: 39603346 DOI: 10.1016/j.clnesp.2024.11.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 10/25/2024] [Accepted: 11/19/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND & AIMS Patients with chronic kidney disease (CKD) often have additional health problems, including sarcopenia and sarcopenic obesity. These conditions involve ectopic fat accumulation within muscles. This ectopic fat deposition reduces muscle quality, leading to weaker muscle strength and poorer physical performance. Persistent hypertriglyceridemia contributes to ectopic fat accumulation. Metabolic abnormalities, including dyslipidemia, are major factors in CKD development. Triglycerides (TG) and muscle quality are thus important factors in CKD management. Recently developed selective peroxisome proliferator-activated receptor α modulator (SPPARMα) hold promises for improving hypertriglyceridemia. However, their effectiveness and impact on muscle quality in CKD patients remain unclear. This study aimed to evaluate the effect of SPPARMα on muscle quality and its efficacy in CKD patients. METHODS This retrospective observational study involved CKD patients with dyslipidemia. We included patients who initiated medications for hypertriglyceridemia. We compared changes in lipid profiles, renal function, and muscle quality, assessed by phase angle, over six months between two groups: those receiving this type of medication and those receiving conventional treatment. RESULTS Among 245 patients diagnosed with CKD and hypertriglyceridemia, 52 started medications for hypertriglyceridemia. Of these, 26 received SPPARMα, and 26 received conventional lipid-lowering medications (statins, ezetimibe, eicosapentaenoic acid, and fibrates). SPPARMα significantly reduced TG (from 296.8 ± 106.1 to 153.0 ± 86.1, p < 0.001) without affecting glomerular filtration rate or urinary protein levels. Conventional treatment also improved TG (from 261.6 ± 89.5 to 173.6 ± 81.3, p < 0.001). Only patients treated with SPPARMα showed significant improvement in muscle quality. Their phase angle increased from 5.41 ± 0.6 to 5.55 ± 0.6 after six months of treatment (p < 0.05). CONCLUSIONS Our study demonstrates that the newly developed SPPARMα significantly lowers TG levels in CKD patients without harming their kidneys. Additionally, only patients treated with SPPARMα showed improvement in muscle quality. These findings suggest that SPPARMα may be a valuable treatment option for CKD patients with dyslipidemia, particularly those with low muscle quality.
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Affiliation(s)
- Yukari Mae
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Tomoaki Takata
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan.
| | - Sosuke Taniguchi
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Yudai Fujino
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Kana Kageyama
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Hinako Hanada
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Takuji Iyama
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Takaaki Sugihara
- School of Health Science, Major in Clinical Laboratory Science, Faculty of Medicine, Tottori University, Japan
| | - Hajime Isomoto
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
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Navaneethan SD, Bansal N, Cavanaugh KL, Chang A, Crowley S, Delgado C, Estrella MM, Ghossein C, Ikizler TA, Koncicki H, St Peter W, Tuttle KR, William J. KDOQI US Commentary on the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD. Am J Kidney Dis 2025; 85:135-176. [PMID: 39556063 DOI: 10.1053/j.ajkd.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 08/04/2024] [Indexed: 11/19/2024]
Abstract
The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the 2024 KDIGO (Kidney Disease: Improving Global Outcomes) guideline for the management of chronic kidney disease (CKD). The KDOQI Work Group reviewed the KDIGO guideline statements and practice points and provided perspective for implementation within the context of clinical practice in the United States. In general, the KDOQI Work Group concurs with several recommendations and practice points proposed by the KDIGO guidelines regarding CKD evaluation, risk assessment, and management options (both lifestyle and medications) for slowing CKD progression, addressing CKD-related complications, and improving cardiovascular outcomes. The KDOQI Work Group acknowledges the growing evidence base to support the use of several novel agents such as sodium/glucose cotransporter 2 inhibitors for several CKD etiologies, and glucagon-like peptide 1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists for type 2 CKD in setting of diabetes. Further, KDIGO guidelines emphasize the importance of team-based care which was also recognized by the work group as a key factor to address the growing CKD burden. In this commentary, the Work Group has also assessed and discussed various barriers and potential opportunities for implementing the recommendations put forth in the 2024 KDIGO guidelines while the scientific community continues to focus on enhancing early identification of CKD and discovering newer therapies for managing kidney disease.
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Affiliation(s)
- Sankar D Navaneethan
- Section of Nephrology, Department of Medicine, Selzman Institute for Kidney Health and Institute of Clinical and Translational Research, Baylor College of Medicine, Houston, Texas; Section of Nephrology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
| | - Nisha Bansal
- Cardiovascular Health Research Unit, Department of Medicine, Washington
| | - Kerri L Cavanaugh
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Alexander Chang
- Department of Population Health Sciences, Geisinger, Danville, Pennsylvania
| | - Susan Crowley
- Section of Nephrology, Department of Medicine, School of Medicine, Yale University, New Haven, Connecticut; Kidney Medicine Section, Medical Services, VA Connecticut Healthcare System, West Haven, Connecticut
| | - Cynthia Delgado
- Nephrology Section, San Francisco Veterans Affairs Health Care System, San Francisco, California; Division of Nephrology, University of California-San Francisco, San Francisco, California
| | - Michelle M Estrella
- Nephrology Section, San Francisco Veterans Affairs Health Care System, San Francisco, California; Division of Nephrology, University of California-San Francisco, San Francisco, California
| | - Cybele Ghossein
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - T Alp Ikizler
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Holly Koncicki
- Division of Nephrology, Mount Sinai Health System, New York, New York
| | - Wendy St Peter
- College of Pharmacy, University of Minnesota, Minneapolis, Minnesota
| | - Katherine R Tuttle
- Institute of Translational Health Sciences, Kidney Research Institute, and Nephrology Division, Washington; School of Medicine, University of Washington, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington
| | - Jeffrey William
- Division of Nephrology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
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Wierzbicki AS. Advances in the pharmacological management of hyperlipidemia through the use of combination therapies. Expert Opin Pharmacother 2025; 26:157-165. [PMID: 39709627 DOI: 10.1080/14656566.2024.2444986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 12/02/2024] [Accepted: 12/17/2024] [Indexed: 12/24/2024]
Abstract
INTRODUCTION Lipid-lowering therapies are well established for the treatment of cardiovascular disease (CVD). Historically monotherapy studies have been performed, but the introduction of statins has led to these drugs being recognized as baseline therapies and to the investigation of combination therapy of both older and newer medications with them. AREAS COVERED Surrogate marker studies have shown additive effects on LDL-C, triglycerides and HDL-C of combination therapies with statins and these have extended to lipoprotein (a). Imaging studies have often shown benefits paralleling lipid studies. However, outcome studies have failed to show added benefits with niacin or fibrates while confirming the benefits of ezetimibe, bempedoic acid and proprotein convertase subtilisin kexin-9 (PCSK-9) inhibitors and icosapent ethyl. EXPERT OPINION Combination therapy for LDL-C in dual combinations is well validated. Data for intervention on triglycerides is limited to icosapent ethyl, but this may exert effects independent of lipids. New drugs targeting triglycerides through apolipoprotein C3 and angiopoietin-like peptides are in development. Studies on combination therapy raising HDL-C have generally disappointed, though cholesterol ester transfer protein (CETP) inhibition remains a target. Lipoprotein (a) is recognized as a CVD risk factor and effective therapies are in development but results on CVD events are lacking.
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Affiliation(s)
- Anthony S Wierzbicki
- Department of Metabolic Medicine/Chemical Pathology Guy's, St Thomas' Hospitals, London, UK
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Li W, Wu C, Li W, Li L. LDL-cholesterol lowering agents (statins and PCSK9 inhibitors) and the risk of intracerebral hemorrhage: A network meta-analysis. J Stroke Cerebrovasc Dis 2025; 34:108224. [PMID: 39755190 DOI: 10.1016/j.jstrokecerebrovasdis.2025.108224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 12/21/2024] [Accepted: 01/01/2025] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND AND PURPOSE Statin therapy reduces the risk of ischemic stroke; however, certain studies have observed an increased incidence of intracerebral hemorrhage (ICH). Moreover, proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors have emerged as a powerful class of lipid-lowering medications, potentially with a lower propensity for causing hemorrhagic events. To investigate this matter further, we conducted a network meta-analysis of randomized controlled trials (RCTs) involving statins and PCSK-9 inhibitors that reported occurrences of ICH. METHODS We performed a literature search of Medline, Web of Science, and The Cochrane Library from database inception until August 2023. All randomized controlled trials of statin therapy and PCSK-9 inhibitors that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. The risk of bias of each included study was assessed by using the Cochrane Handbook for Systematic Reviews of Interventions. We performed network meta-analysis to compare and rank statin and PCSK-9 inhibitors therapies. This study is registered (2023110026. inplasy.com). RESULTS A total of 26251 citations were identified by the search, and 38 potentially eligible articles were included. In total, data from 271411 individuals were analyzed. The data showed that there was not a significant increased risk of intracerebral hemorrhage for all statins and PCSK-9 inhibitors compared with placebo. atorvastatin and rosuvastatin were associated with a lower risk of death than placebo (ORs ranging between 0.79 and 0.82). For risk of intracerebral hemorrhage and mortality. there was not a significant increased risk among all drugs. CONCLUSIONS LDL-Cholesterol lowering agents (statins and PCSK-9 inhibitors) was not associated with a significant increased risk of ICH. Our network meta-analysis provides strong evidence for the safety of statins and PCSK-9 inhibitors, but more studies are needed to further validate this conclusion.
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Affiliation(s)
- Wangwen Li
- Department of Neurology, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China; School of Medicine, Chongqing University, Chongqing 404010, China.
| | - Chuyue Wu
- Department of Neurology, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China; School of Medicine, Chongqing University, Chongqing 404010, China; Chongqing Municipality Clinical Research Center for Geriatric diseases, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China.
| | - Wenkui Li
- Department of Neurology, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China; School of Medicine, Chongqing University, Chongqing 404010, China.
| | - Li Li
- Department of Neurology, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China; School of Medicine, Chongqing University, Chongqing 404010, China.
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Wulandari W, Zakiyah N, Rahayu C, Puspitasari IM, Suwantika AA. Health-related quality of life in hypertensive patients with chronic kidney disease in low and middle-income countries. BMC Nephrol 2025; 26:34. [PMID: 39838338 PMCID: PMC11749374 DOI: 10.1186/s12882-025-03957-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 01/08/2025] [Indexed: 01/23/2025] Open
Abstract
Hypertension and chronic kidney disease (CKD) are interconnected conditions that can significantly affect a person's health-related quality of life (HRQoL). In low- and middle-income countries (LMICs), this disease burden is heightened due to limited health resources and socio-economic challenges. Based on the available literature, this narrative review aims to discuss the HRQoL of hypertensive patients with CKD in LMICs by identifying the current challenges and providing insights into the strategic potential to improve patient's quality of life. This review reveals that the hypertensive population with CKD has a much lower HRQoL than the general population. Various factors, including physical limitations, comorbidities, psychological barriers, logistical challenges, and social support, can influence HRQoL. Limited access to health care, inadequate resources, and a lack of skilled personnel in LMICs further exacerbate these individual challenges. The economic impact of decreased work productivity and increased health costs adds to the disease burden. Improved health access, effective self-management strategies, and social support are needed to improve HRQoL in hypertensive patients with CKD.
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Affiliation(s)
- Wening Wulandari
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21 , Jatinangor, 45363, Indonesia
| | - Neily Zakiyah
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21 , Jatinangor, 45363, Indonesia.
- Centre of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Jatinangor, Indonesia.
| | | | - Irma M Puspitasari
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21 , Jatinangor, 45363, Indonesia
- Centre of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Jatinangor, Indonesia
| | - Auliya A Suwantika
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21 , Jatinangor, 45363, Indonesia
- Centre of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Jatinangor, Indonesia
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Abidor E, Achkar M, Al Saidi I, Lather T, Jdaidani J, Agarwal A, El-Sayegh S. Comprehensive Review of Lipid Management in Chronic Kidney Disease and Hemodialysis Patients: Conventional Approaches, and Challenges for Cardiovascular Risk Reduction. J Clin Med 2025; 14:643. [PMID: 39860649 PMCID: PMC11765848 DOI: 10.3390/jcm14020643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/12/2025] [Accepted: 01/14/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Lipid disorders are very prevalent in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), leading to heightened cardiovascular risk. This review examines the effectiveness of lipid-lowering agents in these populations and explores gaps in the current research. The goal of this review is to assess the efficacy of lipid-lowering therapies in CKD and ESRD patients and identify future research needs. It aims to provide a clearer understanding of how these treatments impact cardiovascular risk in high-risk populations. Methods: We conducted a literature search in Embase, PubMed, Cochrane, and Google Scholar databases using keywords including but not limited to: chronic kidney diseases, dialysis, hemodialysis, dyslipidemia, statins, ezetimibe, and lipid-lowering drugs. Findings from included studies were synthetized to provide an overview of the current management of dyslipidemia in ESRD and HD. Results: Statins show mixed results in CKD and ESRD, with limited benefits in reducing cardiovascular events in dialysis patients. Agents like PCSK9 inhibitors show promising results but require further research, while non-statin therapies like fibrates and omega-3 fatty acids have limited evidence for use in this population. Conclusions: The review underscores the need for further research into lipid-lowering agents in CKD and ESRD patients, highlighting the need for tailored lipid management strategies in vulnerable patients with unique risk factors. More studies are needed to refine treatment strategies and assess the role of exercise and accurate risk calculators in managing cardiovascular outcomes.
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Affiliation(s)
- Erica Abidor
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Michel Achkar
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Ibrahim Al Saidi
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Tanvi Lather
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Jennifer Jdaidani
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Alaukika Agarwal
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Suzanne El-Sayegh
- Department of Medicine, Division of Nephrology, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA
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Zhang Y, Ou G, Peng L, Pan J, Zhang S, Shi J. Genetic association analysis of lipid-lowering drug target genes in chronic kidney disease. Front Endocrinol (Lausanne) 2025; 15:1434145. [PMID: 39877840 PMCID: PMC11772207 DOI: 10.3389/fendo.2024.1434145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 12/23/2024] [Indexed: 01/31/2025] Open
Abstract
Objective The impact of lipid-lowering medications on chronic kidney disease (CKD) remains a subject of debate. This Mendelian randomization (MR) study aims to elucidate the potential effects of lipid-lowering drug targets on CKD development. Methods We extracted 11 genetic variants encoding targets of lipid-lowering drugs from published genome-wide association study (GWAS) summary statistics, encompassing LDLR, HMGCR, PCSK9, NPC1L1, APOB, ABCG5/ABCG8, LPL, APOC3, ANGPTL3, and PPARA. A Mendelian randomization analysis was conducted targeting these drug-related genes. CKD risk was designated as the primary outcome, while estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) were assessed as secondary outcomes. Additionally, mediation analysis was performed utilizing 731 immune cell phenotypes to identify potential mediators. Results The meta-analysis revealed a significant association between ANGPTL3 inhibitors and a reduced risk of CKD (OR [95% CI] = 0.85 [0.75-0.96]). Conversely, LDLR agonists were significantly linked to an increased risk of CKD (OR [95% CI] = 1.11 [1.02-1.22]). Regarding secondary outcomes, lipid-lowering drugs did not significantly affect eGFR and BUN levels. Mediation analysis indicated that the reduction in CKD risk by ANGPTL3 inhibitors was mediated through modulation of the immune cell phenotype, specifically HLA-DR on CD14+ CD16+ monocytes (Mediated proportion: 4.69%; Mediated effect: -0.00899). Conclusion Through drug-targeted MR analysis, we identified a causal relationship between lipid-lowering drug targets and CKD. ANGPTL3 and LDLR may represent promising candidate drug targets for CKD treatment.
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Affiliation(s)
- Yi Zhang
- Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning, China
- Department of Urology, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Guangyang Ou
- Department of Cardiology, Hunan University of Chinese Medicine, Changsha, China
| | - Lei Peng
- Motor Robotics Institute (MRI), South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China
| | - Jian Pan
- Motor Robotics Institute (MRI), South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China
| | - Shaohua Zhang
- Motor Robotics Institute (MRI), South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China
| | - Jianguo Shi
- Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning, China
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Li S, Liu HH, Li JJ. Moderate-Intensity Statin Plus Ezetimibe: Time to Rethink it as an Optimal Initial Lipid-Lowering Strategy. Drugs 2025; 85:51-65. [PMID: 39542994 PMCID: PMC11739249 DOI: 10.1007/s40265-024-02113-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2024] [Indexed: 11/17/2024]
Abstract
Achievement of low-density lipoprotein cholesterol (LDL-C) targets is crucial for the prevention of cardiovascular disease (CVD) in individuals with dyslipidaemia who are at high risk. Current guidelines recommend high-intensity statins at the highest tolerated dose as initial treatment to achieve LDL-C goals. However, the real-world situation is dismal: high-intensity statins are underused and achievement of LDL-C goals is suboptimal. Various challenges exist in the implementation of the recommended initial treatment strategy, including hesitancy to use high-intensity statins, non-adherence, and side effects, and the response to high-intensity statins varies across individuals. Emerging studies have shown another line of lipid-lowering, moderate-intensity statins in combination with ezetimibe, presenting considerable efficacy/effectiveness, along with better safety and adherence compared to statin intensification alone. Here we review the clinical evidence, treatment guidelines and challenges associated with high-intensity statins, and summarise the evidence on the combination therapy, moderate-intensity statin plus ezetimibe, which is the core strategy recommended by the 2023 Chinese Guideline for Lipid Management, as a possible primary treatment to achieve the LDL-C targets across several populations. The upfront use of a moderate-intensity statin plus ezetimibe may improve LDL-C control and lead to the prevention of CVD in real-world settings.
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Affiliation(s)
- Sha Li
- Cardiometabolic Center, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Hui-Hui Liu
- Cardiometabolic Center, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Jian-Jun Li
- Cardiometabolic Center, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China.
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Razi B, Imani D, Aslani S, Reiner Z, Sahebkar A. Statin Therapy and C-reactive Protein in Patients with Kidney Disease: A Systematic Review and Meta-analysis of Randomized Clinical Trials. Curr Drug Targets 2025; 26:132-145. [PMID: 39318006 DOI: 10.2174/0113894501302428240909150925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 08/02/2024] [Accepted: 08/13/2024] [Indexed: 09/26/2024]
Abstract
BACKGROUND Increased levels of inflammation markers in patients with kidney disease, particularly chronic kidney disease (CKD) is an important risk factor. This study explored whether the effect of more potent statins on inflammation in CKD patients is dose-dependent, whether there is any difference between the hydrophilic and lipophilic statins concerning their effects on inflammation markers in patients with CKD, and whether the duration of treatment with statins has any effect on markers of inflammation in these patients. METHODS A systematic literature search of Scopus, PubMed, and ISI Web of Science databases from inception to August 2022 was performed. Eligible studies were stratified based on a target population, intervention duration, dosage and type of statins (high intensity statin and moderate/ low intensity), and solubility of statins. Publication bias was evaluated using Begg's regression asymmetry test for visual inspection of funnel plots. Non-linear effects of dosage of statins and treatment duration were also examined by fractional polynomial modeling. RESULTS Meta-analysis of 10 RCTs (12 studies) on 264 patients with kidney disease and 254 controls showed a significant hs-CRP lowering effect of the dose of statin. Both hydrophilic and lipophilic statins had significant hs-CRP lowering effects. Meta-analysis of 6 publications (7 studies) evaluating the impact of statins on CRP in 235 patients and 197 control subjects showed a significant negative association between treatment with statins group and CRP levels. CONCLUSION Statin treatment decreases significantly the levels of CRP and hs-CRP in patients with kidney disease.
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Affiliation(s)
- Bahman Razi
- Department of Laboratory Sciences and Hematology, Faculty of Paramedicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Danyal Imani
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Aslani
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, 3168, Australia
- Department of Molecular and Translational Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, 3168, Australia
| | - Zeljko Reiner
- Department of Internal Medicine, University Hospital Center Zagreb, University of Zagreb, Kišpatićeva 12, Zagreb, Croatia
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Gallo A, Le Goff W, Santos RD, Fichtner I, Carugo S, Corsini A, Sirtori C, Ruscica M. Hypercholesterolemia and inflammation-Cooperative cardiovascular risk factors. Eur J Clin Invest 2025; 55:e14326. [PMID: 39370572 PMCID: PMC11628670 DOI: 10.1111/eci.14326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 09/02/2024] [Indexed: 10/08/2024]
Abstract
BACKGROUND Maintaining low concentrations of plasma low-density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation. RESULTS Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti-inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid-lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C-reactive protein appears to be independent of the magnitude of LDLc lowering. CONCLUSION Identifying clinical biomarkers of inflammation (e.g. interleukin-6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.
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Affiliation(s)
- Antonio Gallo
- Lipidology and Cardiovascular Prevention Unit, Department of Nutrition, APHP, Hôpital Pitié‐SalpètriêreSorbonne Université, INSERM UMR1166ParisFrance
| | - Wilfried Le Goff
- Lipidology and Cardiovascular Prevention Unit, Department of Nutrition, APHP, Hôpital Pitié‐SalpètriêreSorbonne Université, INSERM UMR1166ParisFrance
| | - Raul D. Santos
- Academic Research Organization Hospital Israelita Albert Einstein and Lipid Clinic Heart Institute (InCor)University of Sao Paulo Medical School HospitalSao PauloBrazil
| | - Isabella Fichtner
- Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”Università degli Studi di MilanoMilanItaly
| | - Stefano Carugo
- Department of Cardio‐Thoracic‐Vascular DiseasesFoundation IRCCS Cà Granda Ospedale Maggiore PoliclinicoMilanItaly
- Department of Clinical Sciences and Community HealthUniversità degli Studi di MilanoMilanItaly
| | - Alberto Corsini
- Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”Università degli Studi di MilanoMilanItaly
| | - Cesare Sirtori
- Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”Università degli Studi di MilanoMilanItaly
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”Università degli Studi di MilanoMilanItaly
- Department of Cardio‐Thoracic‐Vascular DiseasesFoundation IRCCS Cà Granda Ospedale Maggiore PoliclinicoMilanItaly
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Canney M, Atiquzzaman M, Zheng Y, Induruwage D, Zhao Y, Er L, Fordyce CB, Barbour SJ. Evaluating the risk of cardiovascular events associated with different immunosuppression treatments for glomerular diseases. Kidney Int 2025; 107:143-154. [PMID: 39515645 DOI: 10.1016/j.kint.2024.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 09/14/2024] [Accepted: 10/02/2024] [Indexed: 11/16/2024]
Abstract
Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials.
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MESH Headings
- Humans
- Male
- Female
- Retrospective Studies
- Middle Aged
- Immunosuppressive Agents/adverse effects
- Adult
- Glomerular Filtration Rate
- British Columbia/epidemiology
- Cardiovascular Diseases/epidemiology
- Cardiovascular Diseases/chemically induced
- Cardiovascular Diseases/immunology
- Glomerulosclerosis, Focal Segmental/immunology
- Glomerulosclerosis, Focal Segmental/epidemiology
- Glomerulosclerosis, Focal Segmental/drug therapy
- Glomerulosclerosis, Focal Segmental/chemically induced
- Glomerulonephritis, Membranous/drug therapy
- Glomerulonephritis, Membranous/immunology
- Glomerulonephritis, Membranous/epidemiology
- Risk Factors
- Glomerulonephritis, IGA/immunology
- Glomerulonephritis, IGA/drug therapy
- Glomerulonephritis, IGA/complications
- Glomerulonephritis, IGA/epidemiology
- Aged
- Risk Assessment
- Nephrosis, Lipoid/drug therapy
- Nephrosis, Lipoid/immunology
- Nephrosis, Lipoid/epidemiology
- Nephrosis, Lipoid/diagnosis
- Nephrosis, Lipoid/complications
- Calcineurin Inhibitors/adverse effects
- Calcineurin Inhibitors/administration & dosage
- Mycophenolic Acid/adverse effects
- Glomerulonephritis/immunology
- Glomerulonephritis/epidemiology
- Glomerulonephritis/chemically induced
- Glomerulonephritis/diagnosis
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Affiliation(s)
- Mark Canney
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Inflammation and Chronic Disease Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Mohammad Atiquzzaman
- BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada; Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Yuyan Zheng
- BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada
| | - Dilshani Induruwage
- BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada
| | - Yinshan Zhao
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Lee Er
- BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada
| | - Christopher B Fordyce
- Division of Cardiology, Department of Medicine, and Centre for Cardiovascular Innovation, University of British Columbia, Vancouver, British Columbia, Canada
| | - Sean J Barbour
- BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada; Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
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Yang T, Li W, Chen W, Zhu D, Ren Y, Huang X. Protocol for a systematic review and meta-analysis of the combination of ezetimibe and statins for hyperlipidemia. PLoS One 2024; 19:e0312588. [PMID: 39715179 PMCID: PMC11666007 DOI: 10.1371/journal.pone.0312588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 10/09/2024] [Indexed: 12/25/2024] Open
Abstract
INTRODUCTION Hyperlipidemia is increasingly recognized as a significant global health issue, often associated with conditions such as hypertension, diabetes, and obesity. While statins are frequently prescribed to manage lipid levels, recent studies indicate that reliance solely on statin therapy may present certain disadvantages, including prolonged treatment durations, the potential for drug resistance, and various adverse effects. Research indicates that the combination of ezetimibe and statins demonstrates a favorable therapeutic effect in the management of hyperlipidemia. However, existing studies have not consistently confirmed these benefits, and there is no current meta-analysis available. As a result, we will perform a meta-analysis to assess the effectiveness and safety of the combination of ezetimibe and statins in managing hyperlipidemia, aiming to offer evidence-based medical guidance for clinical practice. METHODS AND ANALYSIS The systematic review and meta-analysis will adhere to the PRISMA guidelines for systematic reviews and meta-analyses. We will search for randomized controlled trials that investigate the efficacy and safety of the combination of ezetimibe and statins in treating hyperlipidemia, based on specific criteria. The following electronic databases will be searched by two researchers for relevant records published up to October 1, 2024: Cochrane Central Register of Controlled Trials (CENTRAL) in Cochrane Library, Embase.com, Web of Science, MEDLINE (via PubMed), Wanfang China Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Chinese Scientific Journal Database (VIP). They will also check references and relevant journals manually. Two independent reviewers will handle screening, data extraction, and quality assessment. Subgroup analysis, sensitivity analysis, and publication bias analysis will be performed to assess consistency and reliability. Review Manager 5.4 will be used for data analysis and synthesis, while the GRADE approach will be employed to evaluate the overall study's evidence quality. EXPECTED RESULTS The findings of this systematic review will be shared with various stakeholders who are interested in the combination of ezetimibe and statins for hyperlipidemia. This will offer valuable insights for researchers undertaking future investigations and for clinical practitioners specializing in the treatment of hyperlipidemia. ETHICS AND DISSEMINATION This study is based on a secondary analysis of the literature, so ethical review approval is not required. The final report will be published in a peer-reviewed journal. STUDY REGISTRATION The protocol of the systematic review has been registered on Open Science Framework, with a registration DOI https://doi.org/10.17605/OSF.IO/TEVUY.
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Affiliation(s)
- Tianfu Yang
- The First People’s Hospital of Fuzhou, Fuzhou, Jiangxi, China
| | - Weijuan Li
- Fuzhou Medical College, Nanchang University, Fuzhou, Jiangxi, China
| | - Weiwei Chen
- Fuzhou Medical College, Nanchang University, Fuzhou, Jiangxi, China
| | - Donghong Zhu
- Department of Respiratory, The Ninth Hospital of Nanchang, Nanchang, Jiangxi, China
| | - Yuxi Ren
- Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Xiongfeng Huang
- Fuzhou Medical College, Nanchang University, Fuzhou, Jiangxi, China
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Pesce F, Vadalà M, Almeida E, Fernandez B, Fouque D, Malyszko J, Schmidt-Ott K, Stenvinkel P, Wheeler DC, Seidu S, Cebrian A, Dimov N, Pardo MB, Ziedina I, Habashi N, Manrique J, Marques SHDM, Gallardo MAV, Shehaj L, Nikolova Vlahova MK, Mendonça L, Ksiazek S, Veltri P, Pezzi G, Patella G, Borelli G, Provenzano M, Gesualdo L. International Nephrology Masterclass in Chronic Kidney Disease: Rationale, Summary, and Future Perspectives. Life (Basel) 2024; 14:1668. [PMID: 39768375 PMCID: PMC11677536 DOI: 10.3390/life14121668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 11/30/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the population worldwide, accounting for more than 843 million (M) individuals. The prevalence of CKD (844 M patients) is higher than that of diabetes mellitus (422 M patients), cancer (42 M patients), and HIV (37 M patients), but people are often less aware of it. Global expert groups predict reductions in the nephrology workforce in the next decade, with a declining interest in nephrology careers. Over time, KDIGO guidelines have also focused on topics related to the prevention or management of CKD patients in real-life settings. On these premises, a new educational program with international experts in the field of nephrology took place from November 2022 until March 2023 in Milan, Italy. This multinational masterclass provided an educational platform providing unbiased education on diagnosis and treatment by sharing the most recent research data on CKD and comorbidities, therefore creating a snowball effect to increase the implementation of best practices worldwide, using examples from 'real-life' patient outcomes. This paper provides an overview of the International Nephrology Masterclass (INM) concept, summarizing the key lectures and discussions, and giving an outline of future key developments.
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Affiliation(s)
- Francesco Pesce
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
- Division of Renal Medicine, Ospedale Isola Tiberina-Gemelli, 00816 Rome, Italy;
| | - Maria Vadalà
- Division of Renal Medicine, Ospedale Isola Tiberina-Gemelli, 00816 Rome, Italy;
| | | | | | - Denis Fouque
- University Claude Bernard Lyon, 69100 Villeurbanne, France
| | | | - Kai Schmidt-Ott
- Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany;
| | | | | | - Samuel Seidu
- Leicester City Clinical Commissioning Group, Leicester LE1 6NB, UK;
| | - Ana Cebrian
- Cartagena Casco Health Center, 30201 Murcia, Spain;
| | - Nikolay Dimov
- Nephrology Clinic, University Hospital “Sv. Georgi”, 4002 Plovdiv, Bulgaria;
| | - Marta Blanco Pardo
- División of Nephrology, A Coruña University Hospital, 15006 A Coruña, Spain;
| | | | - Nayaf Habashi
- Department of Nephrology, HaEmeq Hospital Afula, Afula 1834111, Israel;
| | - Joaquin Manrique
- Servicio de Nefrología, Complejo Hospitalario de Navarra, 31008 Pamplona, Spain;
| | | | | | - Larisa Shehaj
- Department of Nephrology, Faculty of Medicine, Bezmialem Vakif University, Istanbul 34093, Türkiye;
| | | | - Luis Mendonça
- Unit of Cardiovascular Research and Development—Unic@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;
| | - Sara Ksiazek
- 6th Medical Department of Internal Medicine with Nephrology & Dialysis, Clinic Ottakring, 1160 Vienna, Austria;
| | - Pierangelo Veltri
- Department of Computer Science, Modeling, Electronics and Systems Engineering, University of Calabria, 87036 Rende, Italy;
| | - Giuseppe Pezzi
- Department of Medical and Surgical Sciences, University of Catanzaro, 88100 Catanzaro, Italy;
| | - Gemma Patella
- Department of Nephrology, Azienda Sanitaria Provinciale, 87100 Cosenza, Italy;
| | - Greta Borelli
- Nephrology, Dialysis and Renal Transplant Unit, IRCSS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Michele Provenzano
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
| | - Loreto Gesualdo
- Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, 70121 Bari, Italy;
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40
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Alhabeeb W, Elasfar A, Kinsara AJ, Aljizeeri A, Jelaidan I, Alghalayini K, AlKheraiji MF, Akbar M, Lawand S, Alyousif SM, Alsifri S, Hassan T. A Saudi Heart Association Position Statement on Cardiovascular Diseases and Diabetes Mellitus. J Saudi Heart Assoc 2024; 36:385-407. [PMID: 39822337 PMCID: PMC11737320 DOI: 10.37616/2212-5043.1407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 11/04/2024] [Accepted: 11/07/2024] [Indexed: 01/19/2025] Open
Abstract
Background Cardiovascular disease (CVD) and diabetes mellitus are prominent public health concerns in Saudi Arabia owing to their increasingly high prevalence and burden. Based on this, the Saudi Heart Association (SHA) set out to develop an official position statement on CVD and diabetes mellitus, with a focus on the prevention and management of these conditions and relevant special populations in the context of Saudi Arabia. Methods A multidisciplinary panel of experts met under the auspices of the SHA in a series of meetings to review and discuss available evidence on the prevention and management of comorbid CVD and diabetes mellitus. Specialized subcommittees reviewed the data and offered context-specific recommendations (taking into account Saudi population characteristics, local healthcare system, available resources and medical expertise), which were later approved by the full expert panel. Results and conclusions The prevalence of diabetes mellitus and CVD is alarming in the Saudi Arabian population. Diabetes mellitus and CVD are interconnected on several levels, including cellular and molecular events as well as epigenetic and genetic mechanisms. Screening for CVD is a priority for patients with diabetes and concomitant risk factors. The expert panel also recommends aggressive management of high blood pressure and dyslipidemia in addition to lifestyle changes and achieving glycemic targets for the prevention of CVD in patients with diabetes. Some glucose-lowering drug classes, namely SGLT2-inhibitors and GLP-1 receptor agonists, offer significant benefits on the level of cardiovascular risk reduction and are thus a powerful addition to the clinical management armamentarium in CVD and diabetes. Special consideration is also advised for patient populations with distinct clinical presentation and needs, such as coronary artery disease, heart failure, and chronic kidney disease, among others.
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Affiliation(s)
- Waleed Alhabeeb
- Department of Cardiac Sciences, King Saud University, Riyadh,
Saudi Arabia
| | | | - Abdulhalim J. Kinsara
- Ministry of National Guard Health Affairs, Jeddah,
Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, COM-WR, Jeddah,
Saudi Arabia
- Department of Cardiology, King Abdullah International Research Center, Jeddah,
Saudi Arabia
| | - Ahmed Aljizeeri
- King Abdulaziz Cardiac Center, Ministry of the National Guard Health Affairs, Riyadh,
Saudi Arabia
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh,
Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh,
Saudi Arabia
| | - Ibrahim Jelaidan
- Ministry of National Guard Health Affairs, Jeddah,
Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, COM-WR, Jeddah,
Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh,
Saudi Arabia
| | | | | | - Mousa Akbar
- Al-Sabah Hospital, Ministry of Health,
Kuwait
| | - Sameh Lawand
- Senior Consultant Interventional Cardiologist at Dallah Hospital, Riyadh,
Saudi Arabia
| | - Sarah M. Alyousif
- Al-Sabah Hospital, Ministry of Health,
Kuwait
- Adult Cardiology Pharmaceutical Care Department, Ministry of National Guard - Health Affairs, Riyadh,
Saudi Arabia
- College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh,
Saudi Arabia
| | - Saud Alsifri
- Endocrinology Department, Alhada Armed Forces Hospital, Taif,
Saudi Arabia
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Elías-López D, Vedel-Krogh S, Kobylecki CJ, Wadström BN, Nordestgaard BG. Impaired Renal Function With Higher Remnant Cholesterol Related to Risk of Atherosclerotic Cardiovascular Disease: A Cohort Study. Arterioscler Thromb Vasc Biol 2024; 44:2647-2658. [PMID: 39445427 DOI: 10.1161/atvbaha.124.321387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 10/01/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND Chronic kidney disease confers a high risk of atherosclerotic cardiovascular disease (ASCVD), partly due to hyperlipidemia. Although statins reduce the risk of ASCVD in chronic kidney disease, residual risk persists. We investigated whether higher remnant cholesterol is associated with an increased risk of ASCVD in statin users and nonusers with impaired renal function. METHODS We included 107 925 individuals from CGPS (Copenhagen General Population Study) initiated in 2003 to 2015, of whom 10 427 had impaired renal function (estimated glomerular filtration rate, <60 mL/min per 1.73 m2). Remnant cholesterol was calculated from a standard lipid profile. ASCVD was myocardial infarction, coronary heart disease death, ischemic stroke, coronary artery bypass graft, or percutaneous coronary intervention extracted from Danish nationwide health registries from baseline through 2018; individuals with events before the start of follow-up were excluded from relevant analysis. RESULTS In individuals with impaired renal function during up to 15 years of follow-up, 597 were diagnosed with myocardial infarction, 618 with ischemic stroke, and 1182 with ASCVD. In these individuals, a 1-mmol/L (39 mg/dL) higher remnant cholesterol level was associated with multivariable-adjusted hazard ratios of 1.22 (95% CI, 1.05-1.42) for myocardial infarction, 1.16 (95% CI, 0.97-1.38) for ischemic stroke, and 1.21 (95% CI, 1.08-1.36) for ASCVD. Corresponding hazard ratios for ASCVD were 1.40 (95% CI, 1.07-1.83) in statin users and 1.16 (95% CI, 1.01-1.34) in nonusers. Of the 1.36-fold excess risk of ASCVD in impaired versus normal renal function, elevated remnant cholesterol and elevated LDL (low-density lipoprotein) cholesterol explained 25% (95% CI, 2.5%-47%) and 0% in statin users and 8.3% (95% CI, 2.4%-14%) and 14% (95% CI, 6.4%-22%) in nonusers, respectively. CONCLUSIONS Our results suggest that higher remnant cholesterol is a good marker of increased risk of ASCVD in individuals with impaired renal function, while higher LDL cholesterol may not be. Patients with chronic kidney disease who have high levels of remnant cholesterol are identifiable through higher non-HDL (high-density lipoprotein) cholesterol or apoB levels.
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Affiliation(s)
- Daniel Elías-López
- Department of Clinical Biochemistry (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
- The Copenhagen General Population Study (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
- Department of Endocrinology and Metabolism and Research Center of Metabolic Diseases, National Institute of Medical Sciences and Nutrition Salvador Zubirán, México City, México (D.E.-L.)
| | - Signe Vedel-Krogh
- Department of Clinical Biochemistry (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
- The Copenhagen General Population Study (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (S.V.-K., B.N.W., B.G.N.)
| | - Camilla Jannie Kobylecki
- Department of Clinical Biochemistry (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
- The Copenhagen General Population Study (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
| | - Benjamin Nilsson Wadström
- Department of Clinical Biochemistry (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
- The Copenhagen General Population Study (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (S.V.-K., B.N.W., B.G.N.)
| | - Børge Grønne Nordestgaard
- Department of Clinical Biochemistry (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
- The Copenhagen General Population Study (D.E.-L., S.V.-K., C.J.K., B.N.W., B.G.N.), Copenhagen University Hospital, Herlev Gentofte, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (S.V.-K., B.N.W., B.G.N.)
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Tang X, Qian H, Lu S, Huang H, Wang J, Li F, Bian A, Ye X, Yang G, Ma K, Xing C, Xu Y, Zeng M, Wang N. Predictive nomogram model for severe coronary artery calcification in end-stage kidney disease patients. Ren Fail 2024; 46:2365393. [PMID: 38874139 PMCID: PMC11232636 DOI: 10.1080/0886022x.2024.2365393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 06/03/2024] [Indexed: 06/15/2024] Open
Abstract
INTRODUCTION The Agatston coronary artery calcification score (CACS) is an assessment index for coronary artery calcification (CAC). This study aims to explore the characteristics of CAC in end-stage kidney disease (ESKD) patients and establish a predictive model to assess the risk of severe CAC in patients. METHODS CACS of ESKD patients was assessed using an electrocardiogram-gated coronary computed tomography (CT) scan with the Agatston scoring method. A predictive nomogram model was established based on stepwise regression. An independent validation cohort comprised of patients with ESKD from multicentres. RESULTS 369 ESKD patients were enrolled in the training set, and 127 patients were included in the validation set. In the training set, the patients were divided into three subgroups: no calcification (CACS = 0, n = 98), mild calcification (0 < CACS ≤ 400, n = 141) and severe calcification (CACS > 400, n = 130). Among the four coronary branches, the left anterior descending branch (LAD) accounted for the highest proportion of calcification. Stepwise regression analysis showed that age, dialysis vintage, β-receptor blocker, calcium-phosphorus product (Ca × P), and alkaline phosphatase (ALP) level were independent risk factors for severe CAC. A nomogram that predicts the risk of severe CAC in ESKD patients has been internally and externally validated, demonstrating high sensitivity and specificity. CONCLUSION CAC is both prevalent and severe in ESKD patients. In the four branches of the coronary arteries, LAD calcification is the most common. Our validated nomogram model, based on clinical risk factors, can help predict the risk of severe coronary calcification in ESKD patients who cannot undergo coronary CT analysis.
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Affiliation(s)
- Xinfang Tang
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Department of Nephrology, the Affiliated Lianyungang Oriental Hospital of Kangda College of Nanjing Medical University, Lianyungang, China
| | - Hanyang Qian
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Department of Nephrology, Nanjing Tongren Hospital, Nanjing, China
| | - Shijiu Lu
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Hui Huang
- Center for Medical Big Data, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jing Wang
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Fan Li
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Department of Nephrology, Nanjing BenQ Medical Center, Nanjing, China
| | - Anning Bian
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Department of Critical Medicine, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaoxue Ye
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Guang Yang
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Kefan Ma
- Department of Imaging, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Changying Xing
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Yi Xu
- Department of Imaging, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Ming Zeng
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Ningning Wang
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
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Zheng K, Qian Y, Wang H, Song D, You H, Hou B, Han F, Zhu Y, Feng F, Lam SM, Shui G, Li X. Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients. Redox Biol 2024; 78:103389. [PMID: 39486359 PMCID: PMC11563940 DOI: 10.1016/j.redox.2024.103389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2024] Open
Abstract
Patients on maintenance hemodialysis exhibit a notably higher risk of cardio-cerebrovascular complications that constitute the major cause of death. Preceding studies have reported conflicting associations between traditional lipid measures and clinical outcome in dialysis patients. In this prospective longitudinal study, we utilized quantitative lipidomics to elucidate, at molecular resolution, changes in lipidome profiles of erythrocyte and plasma samples collected from maintenance hemodialysis patients followed up for 86 months (≈7 years). Primary outcome was defined as cardiovascular-related deaths or new-onset cardio-cerebrovascular events. Cox regression model uncovered plasma/erythrocyte lipids associated with incident cardio-cerebrovascular events in the erythrocyte cohort (n = 117 patients, 37 events) and plasma cohort (n = 45 patients, 11 events), respectively. Both the erythrocyte lipid panel [PA 40:5, PI 34:2, PC 42:6, AUC = 0.83] and plasma lipid panel [PC O-34:1, GM3 18:1; O2/25:0, TG 44:1(16:1_28:0), AUC = 0.94] significantly improved the prediction of cardio-cerebrovascular-related outcome compared to the base model comprising age, sex and dialysis vintage alone. Our findings underscore the pathophysiological significance of anionic phospholipid accretion in erythrocytes in the development of cardio-cerebrovascular complications in dialysis patients. In particular, distorted membrane lipid asymmetry leads to compromised membrane deformability, aberrant cell-cell interactions and altered glutathione metabolism in the erythrocytes of high-risk individuals even at relatively early stage of hemodialysis. Our findings thus underscore the importance of maintaining the RBC pool to lower the risk of cardio-cerebrovascular complications in dialysis patients.
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Affiliation(s)
- Ke Zheng
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yujun Qian
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; Department of Nephrology, Jiangsu Province Hospital/The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Haiyun Wang
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Dan Song
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Hui You
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Bo Hou
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Fei Han
- Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yicheng Zhu
- Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Feng Feng
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Sin Man Lam
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
| | - Guanghou Shui
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
| | - Xuemei Li
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
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Hobbs FDR, McManus RJ, Taylor CJ, Jones NR, Rahman JK, Wolstenholme J, Kim S, Kwon J, Jones L, Hirst JA, Yu LM, Mort S. Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial. Nat Med 2024; 30:3634-3645. [PMID: 39349629 PMCID: PMC11753262 DOI: 10.1038/s41591-024-03263-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 08/22/2024] [Indexed: 12/15/2024]
Abstract
Chronic kidney disease (CKD) is associated with a substantial risk of progression to end-stage renal disease and vascular events. The nonsteroidal mineralocorticoid receptor antagonist (MRA), finerenone, offers cardiorenal protection for people with CKD and diabetes, but there is uncertainty if the steroidal MRA, spironolactone, provides the same protection. In this prospective, randomized, open, blinded endpoint trial, we assessed the effectiveness of 25 mg spironolactone in addition to usual care or usual care alone for reducing cardiovascular outcomes in stage 3b CKD among an older community cohort (mean age = 74.8 years and s.d. = 8.1). We recruited 1,434 adults from English primary care, of whom 1,372 (96%) were included in the primary analysis. The primary outcome was time from randomization until the first occurrence of death, hospitalization for heart disease, stroke, heart failure, transient ischemic attack or peripheral arterial disease, or first onset of any condition listed not present at baseline. Across 3 years of follow-up, the primary endpoint occurred in 113 of 677 participants randomized to spironolactone (16.7%) and 111 of 695 participants randomized to usual care (16.0%) with no significant difference between groups (hazard ratio = 1.05, 95% confidence interval: 0.81-1.37). Two-thirds of participants randomized to spironolactone stopped treatment within 6 months, predominantly because they met prespecified safety stop criteria. The most common reason for stopping spironolactone was a decrease in the estimated glomerular filtration rate that met prespecified stop criteria (n = 239, 35.4%), followed by participants being withdrawn due to treatment side effects (n = 128, 18.9%) and hyperkalemia (n = 54, 8.0%). In conclusion, we found that spironolactone was frequently discontinued due to safety concerns, with no evidence that it reduced cardiovascular outcomes in people with stage 3b CKD. Spironolactone should not be used for people with stage 3b CKD without another explicit treatment indication. ClinicalTrials.gov registration: ISRCTN44522369 .
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Affiliation(s)
- F D Richard Hobbs
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
| | - Richard J McManus
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Clare J Taylor
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Department of Applied Health Sciences, University of Birmingham, Birmingham, UK
| | - Nicholas R Jones
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
| | - Joy K Rahman
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Jane Wolstenholme
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Sungwook Kim
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Joseph Kwon
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Louise Jones
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Jennifer A Hirst
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Ly-Mee Yu
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Sam Mort
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
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Yen CL, Fan PC, Lee CC, Chen JJ, Chen CY, Tu YR, Chu PH, Hsiao CC, Chen YC, Chang CH. The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients. Atherosclerosis 2024; 399:119042. [PMID: 39531896 DOI: 10.1016/j.atherosclerosis.2024.119042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 10/29/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND AND AIMS Different from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients. METHODS By using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: <70 mg/dL, 70-100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics. RESULTS At 5-year follow-up, the LDL-C < 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69-0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65-0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54-0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80-0.91) compared to LDL-C > 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C > 100 mg/dL in study outcomes. CONCLUSIONS Maintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.
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Affiliation(s)
- Chieh-Li Yen
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pei-Chun Fan
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Chia Lee
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jia-Jin Chen
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chao-Yu Chen
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yi-Ran Tu
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pao-Hsien Chu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Cardiology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Ching-Chung Hsiao
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yung-Chang Chen
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chih-Hsiang Chang
- Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Clinical Medicine Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Lolekha P, Khovidhunkit W, Deerochanawong C, Thongtang N, Boonyasirinant T, Rattarasarn C, Chutinet A, Ophascharoensuk V, Somlaw N, Sitthisook S, Suntorntham S, Nitiyanant W, Krittayaphong R. 2024 The Royal College of Physicians of Thailand (RCPT) clinical practice guidelines on management of dyslipidemia for atherosclerotic cardiovascular disease prevention. ASIAN BIOMED 2024; 18:246-267. [PMID: 39697215 PMCID: PMC11650434 DOI: 10.2478/abm-2024-0033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
Background The Royal College of Physicians of Thailand (RCPT) published a Clinical Practice Guideline on Pharmacologic Therapy of Dyslipidemia for Atherosclerotic Cardiovascular Disease (ASCVD) Prevention in 2016. The availability of newer classes of medications for dyslipidemia, supported by extensive clinical research findings, indicates a significant need for the updating of the existing clinical practice guideline. Objectives To serve as guidelines on the management of dyslipidemia for Thai adults. Methods The RCPT Dyslipidemia Guidelines Committee was established with representatives from selected professional societies to revise the 2016 Guideline by critically reviewing the latest evidence. Meetings were conducted from August to December 2023, culminating in a public hearing that engaged various stakeholders in January 2024. The final Thai version received approval in April 2024, while the English translation was completed in October 2024. Results Lifestyle modifications and statins remain the cornerstone of therapy for dyslipidemia in adults across various clinical settings. Emerging evidence regarding newer classes of lipid-lowering medications indicates that these treatments are effective in lowering LDL-cholesterol levels and reducing atherosclerotic cardiovascular events. This suggests that they may serve as an add-on therapy for individuals who cannot achieve target levels or who are at high risk for future cardiovascular events. The Thai CV Risk Score is recommended due to its specificity for the Thai population. Conclusions The 2024 updated clinical practice guidelines establish a framework, provide recommendations, and serve as a comprehensive resource for the contemporary management of dyslipidemia in adults, with the goal of preventing ASCVD in Thailand.
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Affiliation(s)
- Praween Lolekha
- Department of Medicine, Thammasat University, Patrhumthani12121, Thailand
| | - Weerapan Khovidhunkit
- Department of Medicine, King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok10330, Thailand
| | | | - Nuntakorn Thongtang
- Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok10700, Thailand
| | | | - Chatchalit Rattarasarn
- Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok10400, Thailand
| | - Aurauma Chutinet
- Department of Medicine, King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok10330, Thailand
| | | | - Nicha Somlaw
- Department of Medicine, King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok10330, Thailand
| | - Surapun Sitthisook
- Department of Medicine, King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok10330, Thailand
| | | | - Wannee Nitiyanant
- Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok10700, Thailand
| | - Rungroj Krittayaphong
- Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok10700, Thailand
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Belay KE, Feleke Y, Alemneh TA, Haile AM, Abebe DG. Social Determinants of Health for Cardiovascular-Kidney-Metabolic Syndrome Among Patients With Diabetes. J Endocr Soc 2024; 9:bvae208. [PMID: 39669651 PMCID: PMC11635457 DOI: 10.1210/jendso/bvae208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Indexed: 12/14/2024] Open
Abstract
Context Cardiovascular-kidney-metabolic (CKM) syndrome is a recently introduced term that is a complex disease consisting of cardiovascular disease, renal disease, obesity, and diabetes. The association of social determinants of health (SDOH) with CKM syndrome is not fully known. Objective We aimed to assess SDOH affecting CKM syndrome among adult patients with diabetes at follow-up at a tertiary hospital in Ethiopia. Methods A cross-sectional hospital-based study was used. Data were collected using a Kobo toolbox and entered into SPSS version 29 for further analysis. Results A total of 422 adult patients with diabetes were included in this study. The mean ± SD age of the patients was 54.14 ± 13.74 years. Fifty-two percent of the patients were male. In this study, 52.4% had cardiovascular kidney metabolic syndrome. Male patients (AOR: 1.73; 95% CI, 1.01-2.94), lost to follow-up for more than a year due to lack of money (AOR: 2.69; 95% CI, 1.01-7.22), missed an appointment due to lack of transportation in the past 1 year (AOR: 2.98; 95% CI, 1.21-7.33), were patients with disability (AOR: 1.97; 95% CI, 1.12-3.48), had hypertension (AOR: 3.12; 95% CI, 1.85-5.28), had obesity (AOR: 2.27, 95% CI, 1.17, 4.40), and were in retirement (AOR: 2.12; 95% CI, 1.04-4.30) these being more significantly associated with CKM syndrome. Conclusion More than half of patients had CKM syndrome. More attention should be given to SDOH, including male sex, financial constraints, transportation issues, disability, and retirement.
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Affiliation(s)
- Kibret Enyew Belay
- Department of Internal Medicine, Endocrinology and Metabolism Unit, Addis Ababa University, Addis Ababa 1000, Ethiopia
| | - Yeweyenhareg Feleke
- Department of Internal Medicine, Endocrinology and Metabolism Unit, Addis Ababa University, Addis Ababa 1000, Ethiopia
| | - Theodros Aberra Alemneh
- Department of Internal Medicine, Endocrinology and Metabolism Unit, Addis Ababa University, Addis Ababa 1000, Ethiopia
| | - Asteway Mulat Haile
- Department of Internal Medicine, Addis Ababa University, Addis Ababa 1000, Ethiopia
| | - Dawit Girma Abebe
- Department of Internal Medicine, Alert Specialized Hospital, Addis Ababa 1000, Ethiopia
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Olmastroni E, Scotti S, Galimberti F, Xie S, Casula M. Ezetimibe: Integrating Established Use with New Evidence - A Comprehensive Review. Curr Atheroscler Rep 2024; 27:10. [PMID: 39585530 DOI: 10.1007/s11883-024-01248-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/31/2024] [Indexed: 11/26/2024]
Abstract
PURPOSE OF REVIEW To consolidate key information on the efficacy and safety of ezetimibe, with a focus on the latest evidence. RECENT FINDINGS While ezetimibe has long been used alongside statins to help achieve lipid goals when statins are insufficient or in statin-intolerant patients, recent studies confirm and extend its benefits. Ezetimibe, when added to statins, is now recognized as an effective option for high-risk cardiovascular patients. Additionally, for those intolerant to statins, it can be combined with bempedoic acid, offering significant LDL cholesterol reduction. Ezetimibe's favourable tolerability, with fewer side effects than statins, along with the availability of fixed-dose combinations, enhances both treatment efficacy and patient adherence. Overall, this review underscores ezetimibe's evolving role in lipid management, providing valuable guidance for optimizing cardiovascular risk reduction strategies.
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Affiliation(s)
- Elena Olmastroni
- Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy
- IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy
| | - Stefano Scotti
- Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy
- IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy
| | | | - Sining Xie
- Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy
| | - Manuela Casula
- Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy.
- IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
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Chen B, Wang X, Pan D, Wang J. Global Trends and Hotspots in the Association between Chronic Kidney Disease and Cardiovascular Diseases: A Bibliometric Analysis from 2010 to 2023. Cardiorenal Med 2024; 15:1-20. [PMID: 39581182 PMCID: PMC11844684 DOI: 10.1159/000542441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 10/29/2024] [Indexed: 11/26/2024] Open
Abstract
INTRODUCTION This study endeavors to evaluate the distribution patterns and research frontiers within the international literature on the association between chronic kidney disease and cardiovascular diseases in the medical field, through bibliometric analysis and visualized information. METHODS The Web of Science Core Collection database was selected as the data source from 2010 to 2023, and articles related to the association between chronic kidney disease and cardiovascular diseases were retrieved. The article data were analyzed through CiteSpace for bibliometric mapping, involving the examination of keywords, references, country/region distributions, and institutional contributions to identify and understand the evolving research dynamics and frontiers in this interdisciplinary field. RESULTS A total of 2,936 publications on the association between chronic kidney disease and cardiovascular diseases were included. The country with the most publications was USA (n = 904), and the institution with the most publications was University of Pennsylvania (n = 116). The most frequent keywords were chronic kidney disease (n = 2,194), cardiovascular disease (n = 1,188), and mortality (n = 604). The top 20 keywords and top 10 references that burst during 2010 to 2023 were listed. CONCLUSION The association between chronic kidney disease and cardiovascular diseases has sparked extensive research, particularly in high-prevalence areas. From 2010 to 2023, publications on the association between chronic kidney disease and cardiovascular diseases show a linear increase. Current research hotspots and frontiers are mainly in cardiovascular-kidney-metabolic syndrome; innovative therapies and drug impact; gut microbiome; Mendelian randomization analysis. Overall, our study offers a comprehensive scientometric analysis of the association between chronic kidney disease and cardiovascular diseases, providing valuable insights for both researchers and healthcare professionals in the field.
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Affiliation(s)
- Binghao Chen
- School of Economics and Management, University of Science and Technology Beijing, Beijing, China
| | - Xiangqiu Wang
- Peking University Health Science Center, Beijing, China,
| | - Dikang Pan
- Vascular Surgery Department, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Jingyu Wang
- Renal Division, Peking University First Hospital, Beijing, China
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50
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Phang CC, Ng LC, Kadir HA, Liu P, Gan S, Choong LH, Tan CS, Bee YM, Lim C. Recurrent Hospitalizations for Fluid Overload in Diabetes with Kidney Failure Treated with Dialysis. Cardiorenal Med 2024; 14:612-623. [PMID: 39510048 DOI: 10.1159/000542446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 10/22/2024] [Indexed: 11/15/2024] Open
Abstract
INTRODUCTION Diabetes mellitus is the most common cause of end-stage kidney disease (ESKD) in Singapore. ESKD patients have high disease burden and are at increased risk of recurrent hospitalizations, including fluid overload. This study aimed to characterize the risk factors associated with readmissions for fluid overload that will identify high-risk hospitalizations for interventions to reduce readmissions. METHODS Retrospective cohort study of all hospitalizations for fluid overload in adults with diabetes and ESKD on dialysis in SingHealth hospitals between 2018 and 2021. Fluid overload was defined by discharge codes for fluid overload, heart failure, pulmonary edema, and generalized edema. Multivariable Cox regression analysis using the Prentice, Williams and Peterson Total Time model was performed for the outcomes of readmissions for fluid overload within 30 days and 90 days of discharge. RESULTS Among 3,234 hospitalizations for fluid overload, readmission for fluid overload within 30 days and 90 days occurred in 585 (18.1%) and 967 (29.9%) hospitalizations, respectively. Ischemic heart disease, peripheral vascular disease, and lower hemoglobin level were independently associated with readmissions for fluid overload within 30 and 90 days. Additionally, heart failure, hemodialysis (compared to peritoneal dialysis), and lack of statin at discharge were associated with increased 90-day readmission risk. CONCLUSION Modifiable (hemoglobin level, statin use) and non-modifiable factors (ischemic heart disease, peripheral vascular disease, and heart failure) influenced the risk of readmission for fluid overload. These results may guide risk stratification and inform targeted interventions to reduce avoidable, unplanned readmissions for recurrent fluid overload among individuals with diabetes and ESKD.
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Affiliation(s)
- Chee Chin Phang
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
- SingHealth-Duke NUS Academic Medical Center, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Li Choo Ng
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
- Specialty Nursing, Singapore General Hospital, Singapore, Singapore
| | - Hanis Abdul Kadir
- Health Service Research Unit, Singapore General Hospital, Singapore, Singapore
| | - Peiyun Liu
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
- SingHealth-Duke NUS Academic Medical Center, Singapore, Singapore
| | - Sheryl Gan
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
- SingHealth-Duke NUS Academic Medical Center, Singapore, Singapore
| | - Lina HuiLin Choong
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
- SingHealth-Duke NUS Academic Medical Center, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chieh Suai Tan
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
- SingHealth-Duke NUS Academic Medical Center, Singapore, Singapore
| | - Yong Mong Bee
- SingHealth-Duke NUS Academic Medical Center, Singapore, Singapore
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Cynthia Lim
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
- SingHealth-Duke NUS Academic Medical Center, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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