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Bozkurt B, Rossignol P, Vassalotti JA. Albuminuria as a diagnostic criterion and a therapeutic target in heart failure and other cardiovascular disease. Eur J Heart Fail 2025. [PMID: 40425519 DOI: 10.1002/ejhf.3683] [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: 01/22/2025] [Revised: 04/01/2025] [Accepted: 04/17/2025] [Indexed: 05/29/2025] Open
Abstract
The high disease burden and bidirectional relationship of chronic kidney disease (CKD), heart failure (HF) and other cardiovascular disease (CVD) necessitate the need for early diagnosis of these diseases. While current screening and detection methods are recommended by CKD and CVD guidelines, their adoption in practice is low. Urine albumin-to-creatinine ratio (uACR) is recognized as a diagnostic marker for CKD and a prognostic marker for CKD progression, HF and CVD outcomes, therefore albuminuria changes have been accepted as a surrogate outcome for kidney and cardiovascular endpoints. Furthermore, clinical trials investigating guideline-directed medical therapies have shown that uACR reductions are accompanied by risk reductions for cardiovascular, HF and other CKD outcomes. However, uACR is not routinely measured in patients at risk of kidney and heart disease, and its utility for detection, risk stratification and prediction models may not be fully appreciated in routine clinical practice. This review will discuss the effectiveness and implications of uACR screening as a method for heart and kidney disease diagnosis and risk assessment.
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Affiliation(s)
- Biykem Bozkurt
- Department of Medicine, Cardiology Section, Winters Center for Heart Failure Research, Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX, USA
| | - Patrick Rossignol
- Université de Lorraine, Centre d'Investigations Cliniques-Plurithématique 1433 CHRU de Nancy, U1116 Inserm and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
- Medicine and Nephrology-Dialysis Departments, Princess Grace Hospital, Monaco, Monaco
- Monaco Private Hemodialysis Centre, Monaco, Monaco
- M-CRIN (Monaco Clinical Research Infrastructure Network), Monaco, Monaco
| | - Joseph A Vassalotti
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- National Kidney Foundation, Inc, New York, NY, USA
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Yang Y, Li M, Zou H, Yang P, Wang L, Xu G. Dapagliflozin in diabetic kidney disease patients with different filtration status. Eur J Pharm Sci 2025; 207:107045. [PMID: 39961418 DOI: 10.1016/j.ejps.2025.107045] [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: 10/28/2024] [Revised: 02/13/2025] [Accepted: 02/14/2025] [Indexed: 02/23/2025]
Abstract
BACKGROUND Few studies have discussed the effects and mechanism of dapagliflozin on diabetic kidney disease (DKD) with different glomerular filtration rate (GFR) and systolic blood pressure (SBP). This study aimed to investigate the variation in the eGFR and proteinuria after dapagliflozin treatment in DKD patients with different filtration status and SBP levels. METHODS First, we conducted a cross-sectional study to determined hyperfiltration threshold for the DKD trial. Then, we enrolled 259 DKD patients with an eGFR greater than 70 mL/min/1.73m2 and an albumin-to-creatinine ratio (ACR) between 30 and 200 mg/g to receive treatment with dapagliflozin. Hyperfiltration was defined as the 95th percentile of eGFR above the age- and gender- specific in healthy subjects, DKD patients were divided into hyperfiltration and non-hyperfiltration groups, and SBP > 120 mmHg and ≤ 120 mmHg groups. The eGFR, ACR, and blood and urine electrolytes were measured before and after treatment. RESULTS The mean eGFR change at 2 weeks in the hyperfiltration with SBP > 120 mmHg group was greater than in the non-hyperfiltration with SBP ≤ 120 mmHg group (P = 0.048). The mean ACR reduction values were greater in the non-hyperfiltration with SBP ≤ 120 mmHg group than in the hyperfiltration with SBP > 120 mmHg group at 12 weeks (P = 0.042). There was no difference in other blood or urine electrolytes before and after treatment, except for the fractional excretion of sodium (FENa), which significantly increased after 2 weeks (P < 0.001) and recovered after 8 weeks (P = 0.305). CONCLUSION DKD with non-hyperfiltration with SBP ≤ 120 mmHg had a lower mean eGFR decline and greater decrease in the ACR after treatment. The initial increase in FENa and subsequent decrease after dapagliflozin treatment may be the main mechanism behind the eGFR variation.
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Affiliation(s)
- Yang Yang
- Department of Nephrology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, PR China; Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, PR China
| | - Manna Li
- Department of Nephrology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, PR China
| | - Honghong Zou
- Department of Nephrology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, PR China
| | - Pingping Yang
- Department of endocrinology and metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, PR China
| | - Li Wang
- Department of Nephrology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, PR China
| | - Gaosi Xu
- Department of Nephrology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, PR China.
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Veiga AC, Silva-Aguiar RP, Milanez MIO, Aires RS, Moraes YAC, Campos RR, Bergamaschi CT, Caruso-Neves C, Nishi EE. Renal nerves and hypertension contribute to impaired proximal tubule megalin-mediated albumin uptake in renovascular hypertensive rats. Hypertens Res 2025; 48:1491-1502. [PMID: 39820068 DOI: 10.1038/s41440-025-02100-7] [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: 08/08/2024] [Revised: 11/26/2024] [Accepted: 01/06/2025] [Indexed: 01/19/2025]
Abstract
Proteinuria, especially albuminuria, serves as an independent risk factor for progression in cardiovascular and renal diseases. Clinical and experimental studies have demonstrated that renal nerves contribute to renal dysfunction in arterial hypertension (AH). This study hypothesizes that renal nerves mediate the mechanisms of protein endocytosis by proximal tubule epithelial cells (PTEC) and glomerular function; with dysregulation of the renal nerves contributing to proteinuria in Wistar rats with renovascular hypertension (2-kidney, 1-clip model, 2K-1C). Reduced albumin uptake and increased internalization of endocytic receptor megalin in PTEC were found in both the clipped and contralateral kidneys of 2K-1C rats. Renal denervation (DNx) or hydralazine treatment restored these parameters. Moreover, DNx, but not hydralazine, reduced serum creatinine and recovered podocyte numbers in the contralateral kidney of 2K-1C rats. Thus, our data suggest that renal nerves and high arterial pressure contribute to decreased albumin reabsorption by cellular redistribution of megalin in PTEC, while renal nerves remarkably drive glomerular dysfunction in renovascular hypertension, independently of their effect on blood pressure. Created with BioRender.com.
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Affiliation(s)
- A C Veiga
- Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - R P Silva-Aguiar
- Carlos Chagas Filho Biophysics Institute, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - M I O Milanez
- Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - R S Aires
- Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Y A C Moraes
- Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - R R Campos
- Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - C T Bergamaschi
- Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - C Caruso-Neves
- Carlos Chagas Filho Biophysics Institute, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - E E Nishi
- Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
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Tungsanga S, Nantanawijit R, Kiatamornrak P, Kulvichit W, Ngoensawat U, Tachaboon S, Dinhuzen J, Chaisuriyong W, Komolpis K, Peerapornratana S, Praditpornsilpa K, Tungsanga K, Bello AK, Srisawat N. Utility of a novel point-of-care test for albuminuria in communities at high risk for chronic kidney disease in Thailand. BMJ PUBLIC HEALTH 2025; 3:e001412. [PMID: 40017920 PMCID: PMC11812891 DOI: 10.1136/bmjph-2024-001412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 11/14/2024] [Indexed: 03/01/2025]
Abstract
Introduction Chronic kidney disease (CKD) is a major public health concern, and early detection is crucial to prevent adverse outcomes. Albuminuria is an early marker and key prognostic marker in CKD, but reliable tools for its detection are limited particularly in low resource settings. We tested the utility of a novel, affordable point-of-care test (POCT) for albuminuria among high-risk individuals for CKD. Methods This is a community-based cross-sectional study covering 17 primary subdistrict healthcare units in Ban Phaeo District, Samut Sakhon Province, Thailand. The inclusion criteria were asymptomatic adult participants diagnosed with hypertension, diabetes and/or aged over 60 years. We measured serum creatinine and quantitative urine albumin-creatinine ratio (UACR) and administered POCT urine albumin strip test (Albii, K. BioSciences, Bangkok, Thailand) and urine dipstick test for protein. Participants with albuminuria or estimated glomerular filtration rate (eGFR) by CKD-EPI 2009 equation <60 mL/min/1.73 m2 were considered to have suspected CKD. We evaluated diagnostic performance of POCT urine albumin strip. Results Among 2307 participants, 489 (20.3%) participants had reduced eGFR and/or albuminuria. The median eGFR was 93.23 (87.82, 98.73) mL/min/m2, and the median UACR was 9.15 (5.09, 20.96) mg/g. The POCT urine albumin strip showed a sensitivity of 0.70, specificity of 0.97 and accuracy of 0.92 compared with the quantitative UACR. Conversely, the POCT urine dipstick for protein had poor sensitivity, positive predictive value and accuracy. Conclusion The urine albumin test strip is a highly effective tool to conduct point-of-care identification for early CKD among high-risk populations. Given the test's diagnostic performance and ease of use, such test should be incorporated into health policy.
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Affiliation(s)
- Somkanya Tungsanga
- Medicine, Chulalongkorn University, Bangkok, Thailand
- Medicine, University of Alberta, Edmonton, Alberta, Canada
| | | | | | - Win Kulvichit
- Department of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Umphan Ngoensawat
- Thai Red Cross Society, Bangkok, Thailand
- Chulalongkorn University, Bangkok, Thailand
| | - Sasipa Tachaboon
- Thai Red Cross Society, Bangkok, Thailand
- Chulalongkorn University, Bangkok, Thailand
| | - Janejira Dinhuzen
- Thai Red Cross Society, Bangkok, Thailand
- Chulalongkorn University, Bangkok, Thailand
| | | | - Kittinan Komolpis
- Chulalongkorn University, Bangkok, Thailand
- Research Unit of Chulalongkorn University, Bangkok, Thailand
| | - Sadudee Peerapornratana
- Thai Red Cross Society, Bangkok, Thailand
- Department of Medicine, Chulalongkorn University, Bangkok, Thailand
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Kanumilli N, Miszon M, Schnell O, Groop PH. The role of finerenone in the management of CKD in T2D -Practical considerations for primary care. Prim Care Diabetes 2024; 18:565-573. [PMID: 39284756 DOI: 10.1016/j.pcd.2024.09.001] [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: 04/24/2024] [Revised: 09/11/2024] [Accepted: 09/12/2024] [Indexed: 11/24/2024]
Abstract
The prevalence of diabetes and chronic kidney disease (CKD) is increasing worldwide. Diabetic kidney disease is a chronic condition characterized by a gradual increase in urinary albumin excretion, blood pressure, cardiovascular risk, and a decline in glomerular filtration rate (GFR) that can progress to end-stage kidney disease (ESKD). Individuals with diabetes should be screened for CKD annually. Screening should include both measurement of albuminuria and estimation of GFR (eGFR). The structural changes in diabetic kidney disease in individuals with type 1 diabetes are rather uniform, but the histological picture in those with type 2 diabetes and CKD is on the contrary a mix of changes ranging from minor abnormalities to severe glomerulosclerosis, tubulointerstitial fibrosis, and arteriolohyalinosis. Scarring of the kidneys is closely related to the kidney function. Individuals with diabetes often require multiple therapies to prevent progression of CKD and its associated comorbidities and mortality. Management of cardiorenal risk factors, including lifestyle modification, control of blood glucose, blood pressure, and lipids, use of renin-angiotensin-aldosterone system (RAAS) blockers, use of sodium-glucose co-transporter 2 (SGLT2) inhibitors, and the non-steroidal mineralocorticoid receptor antagonist finerenone in individuals with T2D are the cornerstones of therapy. Primary care physicians (PCPs) play a critical role in identifying individuals with CKD, managing early stages of CKD, and referring those with moderate to severe CKD or rapidly declining kidney function to a nephrologist. Referral to a nephrologist should be considered when certain thresholds for eGFR, albuminuria, proteinuria, hematuria, or hypertension are exceeded. This review summarizes current guidelines for the management of CKD and its complications and highlights the role of PCPs in the care of individuals with CKD.
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Affiliation(s)
| | | | - Oliver Schnell
- Forschergruppe Diabetes e. V., Helmholtz Center, Munich, Germany; Sciarc GmbH, Baierbrunn, Germany.
| | - Per-Henrik Groop
- Department of Nephrology, University of Helsinki and University of Helsinki Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Biomedicum, Helsinki, Finland; Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
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Bragg-Gresham JL, Annadanam S, Gillespie B, Li Y, Powe NR, Saran R. Using Risk Assessment to Improve Screening for Albuminuria among US Adults without Diabetes. J Gen Intern Med 2024:10.1007/s11606-024-09185-9. [PMID: 39557751 DOI: 10.1007/s11606-024-09185-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 10/23/2024] [Indexed: 11/20/2024]
Abstract
BACKGROUND Guidelines currently recommend annual screening for albuminuria only among persons with diabetes mellitus (DM). There is no guidance about albuminuria screening in those with other important risk factors for chronic kidney disease (CKD), such as hypertension and/or family history of kidney disease. We sought to create a risk score that predicts the likelihood of albuminuria in adults without diabetes to prompt earlier detection and management of CKD. METHODS Data from 44,322 participants without diabetes, aged 18 + years from the National Health and Nutrition Examination Surveys 1999-2020 were analyzed. Survey-weighted logistic regression was used to assess associations between individual characteristics and presence of albuminuria (urinary albumin to creatinine ratio [UACR] ≥ 30 mg/g), including interaction terms, in three separate models. The sample was divided equally into development and validation data sets. C-statistics were used to assess model fit. RESULTS The prevalence of albuminuria was 9.7% in the US adult population. Higher odds of albuminuria among the non-diabetic population were observed in females, non-Hispanic Black, and smokers, as well as those with low eGFR, hypertension, cardiovascular disease, prediabetes, low HDL cholesterol, and high uric acid levels. Age showed a J-shaped relationship with albuminuria, with lowest odds for ages 25-64 years. The C-statistic was 0.756 for the developmental and 0.752 for the validation set of the final model. Using this model, screening individuals with a predicted probability of ≥ 5% would capture 85% of individuals with albuminuria. CONCLUSIONS These results suggest that it may be helpful to use a risk score framework for albuminuria screening in people without DM to encourage earlier detection and management of CKD. Longitudinal studies are warranted to confirm this approach along with evaluation of its cost effectiveness.
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Affiliation(s)
- Jennifer L Bragg-Gresham
- Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
| | - Surekha Annadanam
- Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Brenda Gillespie
- Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Yiting Li
- Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA
| | - Neil R Powe
- Department of Medicine, University of California, San Francisco and Priscilla Chan and Mark Zuckerberg San Francisco General Hospital, San Francisco, CA, USA
| | - Rajiv Saran
- Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA
- Department of Epidemiology, University of Michigan, School of Public Health, Ann Arbor, MI, USA
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Młynarska E, Buławska D, Czarnik W, Hajdys J, Majchrowicz G, Prusinowski F, Stabrawa M, Rysz J, Franczyk B. Novel Insights into Diabetic Kidney Disease. Int J Mol Sci 2024; 25:10222. [PMID: 39337706 PMCID: PMC11432709 DOI: 10.3390/ijms251810222] [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: 08/20/2024] [Revised: 09/20/2024] [Accepted: 09/21/2024] [Indexed: 09/30/2024] Open
Abstract
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third of type 1 and nearly half of type 2 diabetes patients. As the leading cause of end-stage renal disease (ESRD) globally, DKD develops through a complex interplay of chronic hyperglycemia, oxidative stress, and inflammation. Early detection is crucial, with diagnosis based on persistent albuminuria and reduced estimated glomerular filtration rate (eGFR). Treatment strategies emphasize comprehensive management, including glycemic control, blood pressure regulation, and the use of nephroprotective agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Ongoing research explores novel therapies targeting molecular pathways and non-coding RNAs. Preventive measures focus on rigorous control of hyperglycemia and hypertension, aiming to mitigate disease progression. Despite therapeutic advances, DKD remains a leading cause of ESRD, highlighting the need for continued research to identify new biomarkers and innovative treatments.
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Affiliation(s)
- Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Dominika Buławska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Witold Czarnik
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Filip Prusinowski
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Magdalena Stabrawa
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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Verma S, Mudaliar S, Greasley PJ. Potential Underlying Mechanisms Explaining the Cardiorenal Benefits of Sodium-Glucose Cotransporter 2 Inhibitors. Adv Ther 2024; 41:92-112. [PMID: 37943443 PMCID: PMC10796581 DOI: 10.1007/s12325-023-02652-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 08/17/2023] [Indexed: 11/10/2023]
Abstract
There is a bidirectional pathophysiological interaction between the heart and the kidneys, and prolonged physiological stress to the heart and/or the kidneys can cause adverse cardiorenal complications, including but not limited to subclinical cardiomyopathy, heart failure and chronic kidney disease. Whilst more common in individuals with Type 2 diabetes, cardiorenal complications also occur in the absence of diabetes. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were initially approved to reduce hyperglycaemia in patients with Type 2 diabetes. Recently, these agents have been shown to significantly improve cardiovascular and renal outcomes in patients with and without Type 2 diabetes, demonstrating a robust reduction in hospitalisation for heart failure and reduced risk of progression of chronic kidney disease, thus gaining approval for use in treatment of heart failure and chronic kidney disease. Numerous potential mechanisms have been proposed to explain the cardiorenal effects of SGLT2i. This review provides a simplified summary of key potential cardiac and renal mechanisms underlying the cardiorenal benefits of SGT2i and explains these mechanisms in the clinical context. Key mechanisms related to the clinical effects of SGLT2i on the heart and kidneys explained in this publication include their impact on (1) tissue oxygen delivery, hypoxia and resultant ischaemic injury, (2) vascular health and function, (3) substrate utilisation and metabolic health and (4) cardiac remodelling. Knowing the mechanisms responsible for SGLT2i-imparted cardiorenal benefits in the clinical outcomes will help healthcare practitioners to identify more patients that can benefit from the use of SGLT2i.
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Affiliation(s)
- Subodh Verma
- Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada.
- Department of Surgery, University of Toronto, Toronto, ON, Canada.
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
| | - Sunder Mudaliar
- Endocrinology/Diabetes Section, Veterans Affairs Medical Centre, San Diego, CA, USA
- Department of Medicine, University of California, San Diego, CA, USA
| | - Peter J Greasley
- Early Discovery and Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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Hu M, Shi J, Lu W. Association between proteinuria and adverse pregnancy outcomes: a retrospective cohort study. J OBSTET GYNAECOL 2023; 43:2126299. [PMID: 36178502 DOI: 10.1080/01443615.2022.2126299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Proteinuria during pregnancy is closely related to the occurrence of adverse pregnancy outcomes. One hundred and forty-two women with proteinuria during pregnancy and followed between January 2018 and December 2020 were evaluated. Based on the 24-h proteinuria value, they were divided as mild (n = 76, 300-1000 mg/day), moderate (n = 39, 1000-3500 mg/day) and severe (n = 27, >3500 mg/day) proteinuria. The rates of prematurity, low birth weight and neonatal asphyxia were significantly higher in the severe proteinuria group than in the mild and moderate groups, while the rates of foetal growth restriction and neonatal intensive care unit admission were significantly higher in the severe compared with the mild proteinuria group (all p < .05). Logistic regression analysis showed that moderate proteinuria (OR = 97.2, 95%CI: 7.1-1334.2, p = .001) and severe proteinuria (OR = 34.0, 95%CI: 1.6-711.0, p = .023) were associated with adverse perinatal outcomes. Compared with mild proteinuria, moderate and severe proteinuria are associated with adverse pregnancy outcomes in perinatal infants.Impact StatementWhat is already known on this subject? The production of proteinuria is closely related to the filtration function of the glomerulus, the reabsorption and secretion function of the renal tubules. For women with normal renal function before pregnancy, such physiological changes are less likely to cause adverse symptoms; however, for women with chronic kidney disease before pregnancy, especially those with significantly impaired renal function, the kidneys often cannot compensate for these physiological changes, which can lead to serious complications for both mother and infant.What do the results of this study add? In our study, logistic regression analysis showed that the severity of proteinuria was independently associated with adverse perinatal outcomes. The ROC curve showed that 24-h proteinuria had a predictive value for adverse perinatal outcomes. Therefore, for patients with urine protein quantification ≥0.3 g/24 h, regular 24-h urine protein quantification during pregnancy could help predict adverse perinatal outcomes and improve prognosis.What are the implications of these findings for clinical practice and/or further research? Proteinuria quantification can be used as one of the factors predicting adverse pregnancy outcomes. Thus, monitoring of urinary protein quantification in women during pregnancy should be strengthened for early detection of renal impairment, then interventions be used to improve maternal and infant outcomes.
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Affiliation(s)
- Minjie Hu
- Department of Nephrology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Junfeng Shi
- Department of Nephrology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wei Lu
- Department of Nephrology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
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Elendu C, John Okah M, Fiemotongha KDJ, Adeyemo BI, Bassey BN, Omeludike EK, Obidigbo B. Comprehensive advancements in the prevention and treatment of diabetic nephropathy: A narrative review. Medicine (Baltimore) 2023; 102:e35397. [PMID: 37800812 PMCID: PMC10553077 DOI: 10.1097/md.0000000000035397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 09/05/2023] [Indexed: 10/07/2023] Open
Abstract
Diabetic nephropathy (DN) is a common and severe complication of diabetes mellitus and is the leading cause of chronic kidney disease (CKD) worldwide. Despite current treatments, many individuals with DN progress to end-stage renal disease (ESRD), requiring dialysis or kidney transplantation. The advancement in our understanding of the pathogenesis of diabetic nephropathy has led to the development of new prevention and treatment strategies. We comprehensively reviewed the literature on advances in the prevention and treatment of DN. We searched PubMed, Scopus, and Web of Science databases for articles published between 2000 and 2023, using keywords such as "diabetic nephropathy," "prevention," "treatment," and "recent advances." The recent advances in the prevention and treatment of DN include novel approaches targeting inflammation and fibrosis, such as inhibitors of the nuclear factor kappa-B (NF-kB) pathway, inhibitors of the transforming growth factor-beta (TGF-beta) pathway, and anti-inflammatory cytokines. Other promising strategies include stem cell therapy, gene therapy, and artificial intelligence-based approaches, such as predictive models based on machine learning algorithms that can identify individuals at high risk of developing DN and guide personalized treatment strategies. Combination therapies targeting multiple disease pathways may also offer the most significant potential for improving outcomes for individuals with DN. Overall, the recent advances in the prevention and treatment of DN represent promising avenues for future research and clinical development. Novel therapies targeting inflammation and fibrosis, stem cell and gene therapies, and artificial intelligence-based approaches all show great potential for improving outcomes for individuals with DN.
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Park SK, Jung JY, Kim MH, Oh CM, Ha E, Yang EH, Lee HC, Shin S, Hwang WY, Lee S, Shin SY, Ryoo JH. Changes in proteinuria and the associated risks of ischemic heart disease, acute myocardial infarction, and angina pectoris in Korean population. Epidemiol Health 2023; 45:e2023088. [PMID: 37817566 PMCID: PMC10867523 DOI: 10.4178/epih.e2023088] [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: 12/22/2022] [Revised: 02/13/2023] [Accepted: 03/14/2023] [Indexed: 10/12/2023] Open
Abstract
OBJECTIVES Proteinuria is widely used to predict cardiovascular risk. However, there is insufficient evidence to predict how changes in proteinuria may affect the incidence of cardiovascular disease. METHODS The study included 265,236 Korean adults who underwent health checkups in 2003-2004 and 2007-2008. They were categorized into 4 groups based on changes in proteinuria (negative: negative → negative; resolved: proteinuria ≥1+ → negative; incident: negative → proteinuria ≥1+; persistent: proteinuria ≥1+ → proteinuria ≥1+). We conducted 6 years of follow-up to identify the risks of developing ischemic heart disease (IHD), acute myocardial infarction (AMI), and angina pectoris according to changes in proteinuria. A multivariate Cox proportional-hazards model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident IHD, AMI, and angina pectoris. RESULTS The IHD risk (expressed as HR [95% CI]) was the highest for persistent proteinuria, followed in descending order by incident and resolved proteinuria, compared with negative proteinuria (negative: reference, resolved: 1.211 [95% CI, 1.104 to 1.329], incident: 1.288 [95% CI, 1.184 to 1.400], and persistent: 1.578 [95% CI, 1.324 to 1.881]). The same pattern was associated with AMI (negative: reference, resolved: 1.401 [95% CI, 1.048 to 1.872], incident: 1.606 [95% CI, 1.268 to 2.035], and persistent: 2.069 [95% CI, 1.281 to 3.342]) and angina pectoris (negative: reference, resolved: 1.184 [95% CI, 1.065 to 1.316], incident: 1.275 [95% CI, 1.160 to 1.401], and persistent: 1.554 [95% CI, 1.272 to 1.899]). CONCLUSIONS Experiencing proteinuria increased the risks of IHD, AMI, and angina pectoris even after proteinuria resolved.
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Affiliation(s)
- Sung Keun Park
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ju Young Jung
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min-Ho Kim
- Department of Preventive Medicine, Graduate School, Kyung Hee University, Seoul, Korea
- Informatization Department, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Chang-Mo Oh
- Department of Preventive Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Eunhee Ha
- Department of Occupational and Environment Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Eun Hye Yang
- Department of Occupational and Environmental Medicine, Kyung Hee University Hospital, Seoul, Korea
| | - Hyo Choon Lee
- Department of Occupational and Environmental Medicine, Kyung Hee University Hospital, Seoul, Korea
| | - Soonsu Shin
- Department of Preventive Medicine, Graduate School, Kyung Hee University, Seoul, Korea
| | - Woo Yeon Hwang
- Department of Obstetrics and Gynecology, Kyung Hee University Hospital, Seoul, Korea
| | - Sangho Lee
- Department of Anesthesiology and Pain Medicine, Kyung Hee University Medical Center, Seoul, Korea
| | - So Youn Shin
- Department of Radiology, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jae-Hong Ryoo
- Department of Occupational and Environmental Medicine, Kyung Hee University School of Medicine, Seoul, Korea
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12
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Naaman SC, Bakris GL. Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression. Diabetes Care 2023; 46:1574-1586. [PMID: 37625003 PMCID: PMC10547606 DOI: 10.2337/dci23-0030] [Citation(s) in RCA: 88] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 06/16/2023] [Indexed: 08/27/2023]
Abstract
Management of diabetic kidney disease (DKD) has evolved in parallel with our growing understanding of the multiple interrelated pathophysiological mechanisms that involve hemodynamic, metabolic, and inflammatory pathways. These pathways and others play a vital role in the initiation and progression of DKD. Since its initial discovery, the blockade of the renin-angiotensin system has remained a cornerstone of DKD management, leaving a large component of residual risk to be dealt with. The advent of sodium-glucose cotransporter 2 inhibitors followed by nonsteroidal mineralocorticoid receptor antagonists and, to some extent, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has ushered in a resounding paradigm shift that supports a pillared approach in maximizing treatment to reduce outcomes. This pillared approach is like that derived from the approach to heart failure treatment. The approach mandates that all agents that have been shown in clinical trials to reduce cardiovascular outcomes and/or mortality to a greater extent than a single drug class alone should be used in combination. In this way, each drug class focuses on a specific aspect of the disease's pathophysiology. Thus, in heart failure, β-blockers, sacubitril/valsartan, a mineralocorticoid receptor antagonist, and a diuretic are used together. In this article, we review the evolution of the pillar concept of therapy as it applies to DKD and discuss how it should be used based on the outcome evidence. We also discuss the exciting possibility that GLP-1 RAs may be an additional pillar in the quest to further slow kidney disease progression in diabetes.
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Affiliation(s)
- Sandra C. Naaman
- Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, IL
| | - George L. Bakris
- Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, IL
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13
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Martinez-Arroyo O, Ortega A, Flores-Chova A, Sanchez-Garcia B, Garcia-Garcia AB, Chaves FJ, Martin-Escudero JC, Forner MJ, Redon J, Cortes R. High miR-126-3p levels associated with cardiovascular events in a general population. Eur J Intern Med 2023; 113:49-56. [PMID: 37080818 PMCID: PMC10271715 DOI: 10.1016/j.ejim.2023.04.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 03/27/2023] [Accepted: 04/12/2023] [Indexed: 04/22/2023]
Abstract
BACKGROUND Endothelial dysfunction is a forerunner of atherosclerosis, leading to cardiovascular disease, and albuminuria is a marker of endothelial dysfunction. Circulating levels of microRNAs are emerging as potential biomarkers for cardiovascular disease. Here we estimate the predictive value of a plasma microRNAs signature associated with albuminuria in the incidence of cardiovascular events. METHODS Plasma microRNAs quantified in hypertensive patients by next generation sequencing were validated in a cohort of patients and controls by real-time quantitative PCR. The microRNAs found to be associated with albuminuria were analysed for their prognostic value in predicting cardiovascular events incidence on a retrospective, population-based study (Hortega Study), using Cox proportional hazard models. RESULTS A plasma microRNA profile was identified in the discovery cohort (n = 48) associated with albuminuria and three microRNAs (miR-126-3p, miR-1260b and miR-374a-5p) were confirmed in the validation cohort (n = 98). The microRNA signature discriminates urinary albumin excretion at baseline (n = 1025), and predicts the incidence of cardiovascular events and coronary heart disease and stroke in a general population retrospective study within a 14-year follow-up (n = 926). High miR-126-3p levels were associated with a shorter time free of both cardiovascular events (HR=1.48, (1.36-1.62), p < 0.0001), as well as coronary artery disease and stroke combined (HR=2.49, (2.19-2.83), p < 0.0001). CONCLUSIONS An increased plasma microRNAs profile was identified in hypertensive patients with albuminuria. Increased miR-126-3p suggest it may serve as a prognostic marker for cardiovascular events in a long-term general population. Further studies will assess the potential role of miR-126-3p as a guide for the status of endothelial dysfunction.
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Affiliation(s)
- Olga Martinez-Arroyo
- Cardiometabolic and Renal Risk Research Group, Biomedical Research Institute of Hospital Clinico de Valencia INCLIVA, Valencia, Spain
| | - Ana Ortega
- Cardiometabolic and Renal Risk Research Group, Biomedical Research Institute of Hospital Clinico de Valencia INCLIVA, Valencia, Spain; CIBERCV (CIBER of Cardiovascular Diseases), Madrid, Spain.
| | - Ana Flores-Chova
- Cardiometabolic and Renal Risk Research Group, Biomedical Research Institute of Hospital Clinico de Valencia INCLIVA, Valencia, Spain
| | - Belen Sanchez-Garcia
- Cardiometabolic and Renal Risk Research Group, Biomedical Research Institute of Hospital Clinico de Valencia INCLIVA, Valencia, Spain
| | | | - Felipe J Chaves
- CIBERDEM (CIBER of Diabetes and Metabolic Diseases), Madrid, Spain; Unit of Genomics and Diabetes, Biomedical Research Institute of Hospital Clinico de Valencia INCLIVA, Valencia, Spain
| | - Juan C Martin-Escudero
- Department of Internal Medicine, Rio Hortega Universitary Hospital, Valladolid, Spain; Department of Medicine, Faculty of Medicine, University of Valladolid, Valladolid, Spain
| | - Maria Jose Forner
- Department of Internal Medicine, University Hospital Clinico, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain
| | - Josep Redon
- Cardiometabolic and Renal Risk Research Group, Biomedical Research Institute of Hospital Clinico de Valencia INCLIVA, Valencia, Spain; Department of Internal Medicine, University Hospital Clinico, Valencia, Spain; CIBEROBN (CIBER of Obesity and Nutrition Physiopathology), Madrid, Spain
| | - Raquel Cortes
- Cardiometabolic and Renal Risk Research Group, Biomedical Research Institute of Hospital Clinico de Valencia INCLIVA, Valencia, Spain.
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14
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Huan JM, Ma XT, Li SY, Hu DQ, Chen HY, Wang YM, Su XY, Su WG, Wang YF. Effect of botanical drugs in improving symptoms of hypertensive nephropathy: Analysis of real-world data, retrospective cohort, network, and experimental assessment. Front Pharmacol 2023; 14:1126972. [PMID: 37089916 PMCID: PMC10113664 DOI: 10.3389/fphar.2023.1126972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 03/13/2023] [Indexed: 04/08/2023] Open
Abstract
Background/aim: Hypertensive nephropathy (HN) is a common complication of hypertension. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy. However, botanical drug prescriptions have not been summarized. The purpose of this study is to develop a prescription for improving hypertensive nephropathy, explore the evidence related to clinical application of the prescription, and verify its molecular mechanism of action.Methods: In this study, based on the electronic medical record data on Hypertensive nephropathy, the core botanical drugs and patients’ symptoms were mined using the hierarchical network extraction and fast unfolding algorithm, and the protein interaction network between botanical drugs and Hypertensive nephropathy was established. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. Hierarchical clustering was used to screen for effective botanical drugs. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Animal experiments were performed at the target and pathway levels to analyze the mechanism.Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. In total, 76 effective compounds were obtained using the K-nearest neighbors model, and seven botanical drugs were identified as Gao Shen Formula by hierarchical clustering. Compared with the classical model, the Area under the curve (AUC) value of the K-nearest neighbors model was the best; retrospective cohort verification showed that Gao Shen Formula reduced serum creatinine levels and Chronic kidney disease (CKD) stage [OR = 2.561, 95% CI (1.025–6.406), p < 0.05]. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1β, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways.Conclusion: In the retrospective cohort, we observed that the clinical application of Gao Shen Formula alleviates the decrease in renal function in patients with hypertensive nephropathy. It is speculated that Gao Shen Formula acts by reducing inflammatory reactions, inhibiting renal damage caused by excessive activation of the renin-angiotensin-aldosterone system, and regulating energy metabolism.
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Affiliation(s)
- Jia-Ming Huan
- School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xi-Ting Ma
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR,China
| | - Si-Yi Li
- School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Dong-Qing Hu
- Medical Services Section, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Hao-Yu Chen
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yi-Min Wang
- School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiao-Yi Su
- School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Wen-Ge Su
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
- *Correspondence: Yi-Fei Wang, ; Wen-Ge Su,
| | - Yi-Fei Wang
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
- *Correspondence: Yi-Fei Wang, ; Wen-Ge Su,
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15
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Khan MS, Shahid I, Anker SD, Fonarow GC, Fudim M, Hall ME, Hernandez A, Morris AA, Shafi T, Weir MR, Zannad F, Bakris GL, Butler J. Albuminuria and Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol 2023; 81:270-282. [PMID: 36653095 DOI: 10.1016/j.jacc.2022.10.028] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 10/03/2022] [Indexed: 01/18/2023]
Abstract
Although chronic kidney disease is characterized by low glomerular filtration rate (GFR) or albuminuria, estimated GFR (eGFR) is more widely utilized as a marker of risk profile in cardiovascular diseases, including heart failure (HF). The presence and magnitude of albuminuria confers a strong prognostic association in forecasting risk of incident HF as well as its progression, irrespective of eGFR. Despite the high prevalence of albuminuria in HF, whether it adds incremental prognostic information in clinical practice and serves as an independent risk marker, and whether there are any therapeutic implications of assessing albuminuria in patients with HF is less well-established. In this narrative review, we assess the potential role of albuminuria in risk profiling for development and progression of HF, strengths and limitations of utilizing albuminuria as a risk marker, its ability to serve in HF risk prediction models, and the implications of adopting albuminuria as an effective parameter in cardiovascular trials and practice.
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Affiliation(s)
- Muhammad Shahzeb Khan
- Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA. https://twitter.com/ShahzebkhanMD
| | - Izza Shahid
- Division of Preventive Cardiology, Department of Cardiology, Houston Methodist Academic Institute, Houston, Texas, USA
| | - Stefan D Anker
- Department of Cardiology (CVK), Charité-Universitätsmedizin Berlin; Berlin Institute of Health Center for Regenerative Therapies, German Center for Cardiovascular Research, Berlin, Germany
| | - Gregg C Fonarow
- Division of Cardiology, University of California, Los Angeles, California, USA
| | - Marat Fudim
- Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA; Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Michael E Hall
- Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Adrian Hernandez
- Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA; Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Alanna A Morris
- Division of Cardiology, Emory University, Atlanta, Georgia, USA
| | - Tariq Shafi
- Division of Nephrology, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Matthew R Weir
- Division of Nephrology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Faiez Zannad
- Université de Lorraine, CIC Inserm, CHRU, Nancy, France
| | - George L Bakris
- Department of Medicine, University of Chicago Medicine, Chicago, Illinois, USA
| | - Javed Butler
- Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA; Baylor Scott and White Research Institute, Dallas, Texas, USA.
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16
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Hu H, Cao M, Sun Y, Jin X, Zhao X, Cong X. Efficacy and Safety of Eplerenone for Treating Chronic Kidney Disease: A Meta-Analysis. Int J Hypertens 2023; 2023:6683987. [PMID: 36938116 PMCID: PMC10019978 DOI: 10.1155/2023/6683987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/08/2023] [Accepted: 03/01/2023] [Indexed: 03/17/2023] Open
Abstract
Background In recent years, a large amount of clinical evidence and animal experiments have demonstrated the unique advantages of mineralocorticoid receptor antagonists (MRA) for treating chronic kidney disease (CKD). Aims Accordingly, the present study aimed to systematically assess the second-generation selective MRAs eplerenone's safety and effectiveness for treating CKD. Methods Four databases (PubMed, The Cochrane Library, Embase, and Web of Science) were searched for randomized controlled trials (RCT) correlated with eplerenone for treating CKD up to September 21, 2022. By complying with the inclusion and exclusion criteria, literature screening, and data extraction were conducted. Results A total of 19 randomized controlled articles involving 4501 cases were covered. As suggested from the meta-analysis, significant differences were reported with the 24-h urine protein (MD = -42.23, 95% confidence interval [CI] = -76.72 to -7.73, P = 0.02), urinary albumin-creatinine ratio (UACR) (MD = -23.57, 95% CI = -29.28 to -17.86, P < 0.00001), the systolic blood pressure (SBP) (MD = -2.73, 95% CI = -4.86 to -0.59, P = 0.01), and eGFR (MD = -1.56, 95% CI = -2.78 to -0.34, P = 0.01) in the subgroup of eplerenone vs placebo. The subgroups of eplerenone vs placebo (MD = 0.13, 95% CI = 0.07 to 0.18, P < 0.00001) and eplerenone vs thiazide diuretic (MD = 0.18, 95% CI = 0.13 to 0.23, P < 0.00001) showed the significantly increased potassium levels. However, no statistical significance was reported between the eplerenone treatment groups and the control in the effect exerted by serum creatinine (MD=0.03, 95% CI = -0.01 to 0.07, P = 0.12) and diastolic blood pressure (DBP) (MD = 0.11, 95% CI = -0.41 to 0.63, P = 0.68). Furthermore, significant risks of hyperkalemia were reported in the eplerenone group (K+ ≥ 5.5 mmol/l, RR = 1.70, 95%CI = 1.35 to 2.13, P=<0.00001; K+≥6.0 mmol/l, RR = 1.61, 95% CIs = 1.06 to 2.44, P = 0.02), respectively. Conclusions Eplerenone has beneficial effects on CKD by reducing urinary protein and the systolic blood pressure, but it also elevates the risk of hyperkalemia.
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Affiliation(s)
- Honglei Hu
- 1Department of Endocrinology, Shandong Zibo Central Hospital, Zibo 255000, China
| | - Mengdie Cao
- 2Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215000, China
| | - Yao Sun
- 1Department of Endocrinology, Shandong Zibo Central Hospital, Zibo 255000, China
| | - Xingqian Jin
- 1Department of Endocrinology, Shandong Zibo Central Hospital, Zibo 255000, China
| | - Xiaodong Zhao
- 1Department of Endocrinology, Shandong Zibo Central Hospital, Zibo 255000, China
| | - Xiangguo Cong
- 2Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215000, China
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17
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Chang YM, Liu WJ, Lee CL, Wang JS. Risk of all-cause mortality in subjects with varying degrees of renal impairment with or without dietary protein restriction. ENDOCRINOL DIAB NUTR 2022; 69:669-676. [PMID: 36470642 DOI: 10.1016/j.endien.2022.11.003] [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: 06/24/2021] [Accepted: 09/05/2021] [Indexed: 06/17/2023]
Abstract
BACKGROUND AND OBJECTIVE Low-protein diet (less than 0.8g/kg/day) has been practiced in the management of chronic kidney disease (estimated glomerular filtration rate [eGFR]<60ml/min/1.73m2 or urine albumin-to-creatinine ratios [UACR] ≥30mg/g) for decades. However, its effect on all-cause mortality is unclear. We investigated the association between a low-protein intake and all-cause mortality in subjects with varying degrees of renal impairment. MATERIALS AND METHODS We analyzed participants in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2010. They were divided into four groups according to their eGFR (≥60 or <60ml/min/1.73m2) and UACR (≥30 or <30mg/g). Daily protein intake of the NHANES participants could be assessed using information from the dietary interview questionnaires. The mortality data was retrieved by linking to the National Death Index till the end of 2011. The hazard ratios for all-cause mortality were evaluated by the weighted Cox proportional hazards regression models. RESULTS A total of 8093 participants were analyzed. During a median follow-up of 4.7 years, participants with UACR≥30mg/g (with or without eGFR<60ml/min/1.73m2) had a higher risk of all-cause mortality compared with those having UACR<30mg/g and eGFR≥60ml/min/1.73m2 (reference group). The higher risk of mortality in participants with UACR≥30mg/g was consistently observed in those with or without a low-protein intake. CONCLUSIONS A low-protein intake was not associated with a lower risk of all-cause mortality in subjects with varying degrees of renal impairment.
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Affiliation(s)
- Yi-Min Chang
- Department of Education, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wei-Ju Liu
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chia-Lin Lee
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jun-Sing Wang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Rong Hsing Research Center for Translational Medicine, Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan; Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
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18
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Park SK, Jung JY, Kim MH, Oh CM, Ha E, Shin SS, Lee HC, Hwang WY, Ryoo JH. The association between changes in proteinuria and the risk of cerebral infarction in the Korean population. Diabetes Res Clin Pract 2022; 192:110090. [PMID: 36122864 DOI: 10.1016/j.diabres.2022.110090] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/06/2022] [Accepted: 09/12/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Proteinuria is a risk factor for cerebral infarction. It is known that proteinuria can change over time. However, published data is scarce for the association between changes in proteinuria and the risk of cerebral infarction. METHOD Study participants were 276,861 Koreans who were assessed for urine dipstick proteinuria both in 2003-2004 and 2007-2008. They were categorized into four groups by changes in proteinuria over 4 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1 + ). We used multivariate adjusted Cox-proportional hazard model in calculating the adjusted hazard ratios (HR) and 95% confidence interval (CI) for cerebral infarction until 2013 according to changes in proteinuria. RESULT Adjusted HR and 95% CI for cerebral infarction significantly increased in order of persistent, incident, and resolved proteinuria, compared with negative proteinuria (negative: reference, resolved: 1.166 [1.009-1.347], incident: 1.345 [1.188-1.522], and persistent: 1.443 [1.089-1.912]). In gender subgroup analysis, men showed the more clear association between changes in proteinuria and the risk of cerebral infarction (negative: reference, resolved: 1.284 [1.057-1.560], incident: 1.351 [1.149-1.589], and persistent: 1.428 [1.014-2.012]). CONCLUSION All types of proteinuria changes were associated with the increased risk of cerebral infarction, even in participants with once manifested but vanishing proteinuria.
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Affiliation(s)
- Sung Keun Park
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea.
| | - Ju Young Jung
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea.
| | - Min-Ho Kim
- Department of Preventive Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea; Informatization Department, Ewha Womans University Seoul Hospital, Seoul, Korea..
| | - Chang-Mo Oh
- Departments of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
| | - Eunhee Ha
- Department of Occupational and Environment Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
| | - Soon Su Shin
- Department of Occupational & Environmental Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea.
| | - Hyo Choon Lee
- Department of Occupational & Environmental Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea.
| | - Woo Yeon Hwang
- Department of Obstetrics and Gynecology, Kyung Hee University Hospital, Seoul, Republic of Korea.
| | - Jae-Hong Ryoo
- Departments of Occupational and Environmental Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
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19
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de Fallois J, Schenk S, Kowald J, Lindner TH, Engesser M, Münch J, Meigen C, Halbritter J. The diagnostic value of native kidney biopsy in low grade, subnephrotic, and nephrotic range proteinuria: A retrospective cohort study. PLoS One 2022; 17:e0273671. [PMID: 36054109 PMCID: PMC9439248 DOI: 10.1371/journal.pone.0273671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 08/12/2022] [Indexed: 11/23/2022] Open
Abstract
Background In nephrotic range proteinuria of adult-onset, kidney biopsy is the diagnostic gold standard in determining the underlying cause of disease. However, in low grade or subnephrotic proteinuria the diagnostic value of kidney biopsy as first-line diagnostics is less well established. Methods We conducted a retrospective analysis of all native kidney biopsies at our institution (n = 639) between 01/2012 and 05/2021 for comparison of histological diagnoses and clinical outcomes stratified by amount of proteinuria at the time of kidney biopsy: A: <300mg/g creatinine (low grade), B: 300-3500mg/g creatinine (subnephrotic), C >3500mg/g creatinine (nephrotic). Results Nephrotic range proteinuria was associated with the highest frequency (49.3%) of primary glomerulopathies followed by subnephrotic (34.4%) and low grade proteinuria (37.7%). However, within the subnephrotic group, the amount of proteinuria at kidney biopsy was linearly associated with renal and overall survival (HR 1.05 per Δ100mg protein/g creatinine (95% CI: 1.02–1.09, p = 0.001)) independent of present histological diagnoses and erythrocyturia. Conclusion Frequency of primary glomerulopathies supports to perform kidney biopsy in patients with subnephrotic proteinuria. These patients have a substantial risk of ESKD and death upon follow-up. Therefore, diagnostic accuracy including histopathology is essential to guide personalized treatment and avert detrimental courses.
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Affiliation(s)
- Jonathan de Fallois
- Medical Department III, Division of Nephrology, University of Leipzig Medical Center, Leipzig, Germany
- * E-mail:
| | - Soeren Schenk
- Medical Department III, Division of Nephrology, University of Leipzig Medical Center, Leipzig, Germany
| | - Jan Kowald
- Medical Department III, Division of Nephrology, University of Leipzig Medical Center, Leipzig, Germany
| | - Tom H. Lindner
- Medical Department III, Division of Nephrology, University of Leipzig Medical Center, Leipzig, Germany
| | - Marie Engesser
- Medical Department III, Division of Nephrology, University of Leipzig Medical Center, Leipzig, Germany
| | - Johannes Münch
- Medical Department III, Division of Nephrology, University of Leipzig Medical Center, Leipzig, Germany
- Departement of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Christof Meigen
- LIFE Child, Hospital for Children and Adolescents, Medical Faculty, Leipzig University, Leipzig, Germany
| | - Jan Halbritter
- Medical Department III, Division of Nephrology, University of Leipzig Medical Center, Leipzig, Germany
- Departement of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
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20
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Hypertension mediated kidney and cardiovascular damage and risk stratification: Redefining concepts. Nefrologia 2022. [DOI: 10.1016/j.nefro.2021.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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21
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Márquez DF, Rodríguez-Sánchez E, de la Morena JS, Ruilope LM, Ruiz-Hurtado G. Hypertension mediated kidney and cardiovascular damage and risk stratification: Redefining concepts. Nefrologia 2022; 42:519-530. [PMID: 36792306 DOI: 10.1016/j.nefroe.2021.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 10/18/2021] [Indexed: 06/18/2023] Open
Abstract
Hypertension mediated organ damage (HMOD) refers to structural or functional changes in arteries or target organs that can be present in long-standing hypertension, but it can be also found in naïve never treated patients. Traditionally, cardiovascular risk is stratified with charts or calculators that tend to underestimate the real cardiovascular risk. The diagnosis of HMOD automatically reclassifies patients to the highest level of cardiovascular risk. Subclinical HMOD can be present already at the diagnosis of hypertension and more than 25% of hypertensives are misclassified with the routine tests recommended by hypertension guidelines. Whether HMOD regression improves cardiovascular outcomes has never been investigated in randomized clinical trials and remains controversial. However, different drugs have been probed with promising results in high cardiovascular risk patients, such as the new antidiabetic or the novel non-steroid mineralocorticoid antagonists. Accordingly, trials have shown that lowering blood pressure reduces cardiovascular events. In this narrative review, we will discuss the role of HMOD in cardiovascular risk stratification, the different types of organ damage, and the evidence available to define whether HMOD can be used as a therapeutic target.
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Affiliation(s)
- Diego Francisco Márquez
- Unidad de Hipertensión Arterial-Servicio de Clínica Médica, Hospital San Bernardo, Salta, Argentina; Instituto de NefroUrología y Nutrición de Salta, Salta, Argentina
| | - Elena Rodríguez-Sánchez
- Cardiorenal Translational Laboratory, Instituto de Investigación Imas12 and Hospital 12 de Octubre, Madrid, Spain
| | - Julián Segura de la Morena
- Cardiorenal Translational Laboratory, Instituto de Investigación Imas12 and Hospital 12 de Octubre, Madrid, Spain; Unidad de Hipertensión Arterial, Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Luis Miguel Ruilope
- Cardiorenal Translational Laboratory, Instituto de Investigación Imas12 and Hospital 12 de Octubre, Madrid, Spain; Unidad de Hipertensión Arterial, Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, Spain; Escuela de Estudios Postdoctorales and Investigación, Universidad Europea de Madrid, Madrid, Spain; CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Gema Ruiz-Hurtado
- Cardiorenal Translational Laboratory, Instituto de Investigación Imas12 and Hospital 12 de Octubre, Madrid, Spain; Unidad de Hipertensión Arterial, Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, Spain; CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain.
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22
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Han E, Kim MK, Im SS, Jang BK, Kim HS. Non-alcoholic fatty liver disease and sarcopenia is associated with the risk of albuminuria independent of insulin resistance, and obesity. J Diabetes Complications 2022; 36:108253. [PMID: 35817677 DOI: 10.1016/j.jdiacomp.2022.108253] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 06/21/2022] [Accepted: 06/28/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Although non-alcoholic fatty liver disease (NAFLD) is associated with metabolic disorders, its influence on albuminuria has not been determined. The aim of this study was to identify the relationship between NAFLD and albuminuria in the general Korean population. METHODS Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) of 2008-2011 were analyzed (n = 1795). Albuminuria was defined as an albumin-to-creatinine ratio of ≥30 mg/g in random spot urine samples. NAFLD was defined as a fatty liver index (FLI) ≥60 or NAFLD liver fat score (LFS) > -0.64. RESULTS A total of 289 (16.1 %) subjects were classified as having albuminuria. Subjects with NAFLD exhibited a higher rate of albuminuria than subjects without NAFLD (crude odds ratios [ORs] = 2.60-2.95, all P < 0.001). Regardless of hypertension, insulin resistance, or obesity, the risk for albuminuria was higher in the NAFLD group than in the group without NAFLD (measured by either FLI or LFS; all P < 0.001). When subjects with NAFLD had sarcopenia, the risk of albuminuria further increased (OR = 4.33-4.64, all P < 0.001). Multiple logistic regression analyses also demonstrated that NAFLD was independently associated with albuminuria (OR = 2.58, 95 % confidence interval [CI] = 1.66-4.02, P < 0.001 for FLI, OR = 1.87, 95 % CI = 1.28-2.75, P = 0.001 for LFS). CONCLUSIONS NAFLD was associated with an increased risk of albuminuria in the general Korean population. This association was independent of hypertension, insulin resistance, chronic kidney disease, diabetes and obesity, and stronger in subjects with sarcopenia.
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Affiliation(s)
- Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Mi Kyung Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Seung-Soon Im
- Department of Physiology, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Hye Soon Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.
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23
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Da Silva Lodge M, Pullen N, Pereira M, Johnson TS. Urinary levels of pro-fibrotic transglutaminase 2 (TG2) may help predict progression of chronic kidney disease. PLoS One 2022; 17:e0262104. [PMID: 35041708 PMCID: PMC8765645 DOI: 10.1371/journal.pone.0262104] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 12/16/2021] [Indexed: 01/04/2023] Open
Abstract
Renal clinical chemistry only detects kidney dysfunction after considerable damage has occurred and is imperfect in predicting long term outcomes. Consequently, more sensitive markers of early damage and better predictors of progression are being urgently sought, to better support clinical decisions and support shorter clinical trials. Transglutaminase 2 (TG2) is strongly implicated in the fibrotic remodeling that drives chronic kidney disease (CKD). We hypothesized that urinary TG2 and its ε-(γ-glutamyl)-lysine crosslink product could be useful biomarkers of kidney fibrosis and progression. Animal models: a rat 4-month 5/6th subtotal nephrectomy model of CKD and a rat 8-month streptozotocin model of diabetic kidney disease had 24-hour collection of urine, made using a metabolic cage, at regular periods throughout disease development. Patients: Urine samples from patients with CKD (n = 290) and healthy volunteers (n = 33) were collected prospectively, and progression tracked for 3 years. An estimated glomerular filtration rate (eGFR) loss of 2-5 mL/min/year was considered progressive, with rapid progression defined as > 5 mL/min/year. Assays: TG2 was measured in human and rat urine samples by enzyme-linked immunosorbent assay (ELISA) and ε-(γ-glutamyl)-lysine by exhaustive proteolytic digestion and amino acid analysis. Urinary TG2 and ε-(γ-glutamyl)-lysine increased with the development of fibrosis in both animal model systems. Urinary TG2 was 41-fold higher in patients with CKD than HVs, with levels elevated 17-fold by CKD stage 2. The urinary TG2:creatinine ratio (UTCR) was 9 ng/mmol in HV compared with 114 ng/mmol in non-progressive CKD, 1244 ng/mmol in progressive CKD and 1898 ng/mmol in rapidly progressive CKD. Both urinary TG2 and ε-(γ-glutamyl)-lysine were significantly associated with speed of progression in univariate logistic regression models. In a multivariate model adjusted for urinary TG2, ε-(γ-glutamyl)-lysine, age, sex, urinary albumin:creatinine ratio (UACR), urinary protein:creatinine ratio (UPCR), and CKD stage, only TG2 remained statistically significant. Receiver operating characteristic (ROC) curve analysis determined an 86.4% accuracy of prediction of progression for UTCR compared with 73.5% for UACR. Urinary TG2 and ε-(γ-glutamyl)-lysine are increased in CKD. In this pilot investigation, UTCR was a better predictor of progression in patients with CKD than UACR. Larger studies are now warranted to fully evaluate UTCR value in predicting patient outcomes.
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Affiliation(s)
- Michelle Da Silva Lodge
- Academic Nephrology Unit and Sheffield Kidney Institute, University of Sheffield Medical School, Sheffield, United Kingdom
| | - Nick Pullen
- Pfizer Global Research and Development, Cambridge, MA, United States of America
| | - Miguel Pereira
- Statistical Sciences and Innovation, UCB Pharma, Slough, United Kingdom
| | - Timothy S. Johnson
- Academic Nephrology Unit and Sheffield Kidney Institute, University of Sheffield Medical School, Sheffield, United Kingdom
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24
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Park YJ, Yang PS, Yu HT, Kim TH, Jang E, Uhm JS, Pak HN, Lee MH, Lip GY, Joung B. Association of proteinuria and hypertension with incident atrial fibrillation in an elderly population: nationwide data from a community-based elderly cohort. J Hypertens 2022; 40:128-135. [PMID: 34857705 PMCID: PMC8654251 DOI: 10.1097/hjh.0000000000002987] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/26/2021] [Accepted: 07/17/2021] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The excess risk of atrial fibrillation in relation to the presence of proteinuria associated with hypertension has not been well elucidated. We aimed to determine the effect of hypertension and/or proteinuria on the incidence of atrial fibrillation. Second, we evaluated whether the associations with temporal changes in proteinuria status on the incidence of atrial fibrillation. METHODS AND RESULTS A total of 85 434 participants with hypertension and 125 912 participants without hypertension with age at least 60 years from the Korea National Health Insurance Service-Senior cohort were included. Amongst controls (participants without proteinuria and hypertension), hypertension only, proteinuria only, and hypertension with proteinuria groups, the adjusted incidences of atrial fibrillation were 0.51, 0.69. 0.78 and 0.99 per 100 person-years, respectively after inverse probability of treatment weighting. Compared with controls, the weighted risks of atrial fibrillation in the hypertension only, proteinuria only and hypertension with proteinuria groups were increased by 37% (hazard ratio 1.37, 95% confidence interval, CI 1.30-1.44, P = 0.001), 55% (hazard ratio 1.55, 95% CI 1.28-1.88, P < 0.001), and 98% (hazard ratio 1.98, 95% CI 1.62-2.43, P < 0.001), respectively. Populations who had proteinuria in the first examination had an increased risk of atrial fibrillation even in the group whereby the proteinuria was resolved on the second examination (hazard ratio 1.36, 95% CI 1.12-2.31, P < 0.001). The presence of proteinuria in first and second analysis had the highest risk of incident atrial fibrillation (hazard ratio 1.61, 95% CI 1.12-2.31). CONCLUSION In conclusion, hypertension and/or proteinuria were associated with increased risk of atrial fibrillation, with the greatest risks when both are present. Proteinuria could be a useful factor for predicting atrial fibrillation development.
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Affiliation(s)
- Yoon Jung Park
- Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul
| | - Pil-Sung Yang
- Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Hee Tae Yu
- Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul
| | - Tae-Hoon Kim
- Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul
| | - Eunsun Jang
- Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul
| | - Jae-Sun Uhm
- Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul
| | - Hui-Nam Pak
- Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul
| | - Moon-Hyoung Lee
- Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul
| | - Gregory Y.H. Lip
- Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
| | - Boyoung Joung
- Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul
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25
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Kociánová E. Why take organ damage in hypertension seriously? VNITRNI LEKARSTVI 2022; 68:303-308. [PMID: 36283821 DOI: 10.36290/vnl.2022.064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
The focus of recent European guidelines has been early initiation of antihypertensive therapy in risk groups, rapid achievement of target blood pressure with fixed combinations of antihypertensive drugs, and the best possible management of an individuals cardiovascular risk. Early intervention in the development of hypertension-mediated organ damage (HMOD) has been shown to have an effect on the subsequent reduction in the risk of cardiovascular events. The point of HMOD origination correlates with the magnitude and duration of blood pressure elevation, and there is no clearly defined boundary from which vascular damage begins to develop. A reduction in blood pressure with pharmacotherapy demonstrably decreases the risk of ischaemic heart disease, stroke, as well as the mortality rate (1). Large clinical trials have consistently shown a significant reduction in the risk of these complications with antihypertensive medications across the entire spectrum from mild to severe hypertension, including hypertension in the elderly as well as isolated systolic hypertension (2). Based on the latest knowledge, a reduction in blood pressure by a mere 5 mm Hg has a cardioprotective effect even in normotensive individuals, which fundamentally changes the view on the diagnosis and definition of hypertension as a disease (3).
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26
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Ballermann BJ, Nyström J, Haraldsson B. The Glomerular Endothelium Restricts Albumin Filtration. Front Med (Lausanne) 2021; 8:766689. [PMID: 34912827 PMCID: PMC8667033 DOI: 10.3389/fmed.2021.766689] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 11/05/2021] [Indexed: 12/29/2022] Open
Abstract
Inflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Another example is the chronic endothelial dysfunction that develops in cardiovascular disease and in metabolic disorders like diabetes. While the glomerular endothelium is a porous sieve that filters prodigious amounts of water and small solutes, it also bars the bulk of albumin and large plasma proteins from passing into the glomerular filtrate. This endothelial barrier function is ascribed predominantly to the endothelial glycocalyx with its endothelial surface layer, that together form a relatively thick, mucinous coat composed of glycosaminoglycans, proteoglycans, glycolipids, sialomucins and other glycoproteins, as well as secreted and circulating proteins. The glycocalyx/endothelial surface layer not only covers the glomerular endothelium; it extends into the endothelial fenestrae. Some glycocalyx components span or are attached to the apical endothelial cell plasma membrane and form the formal glycocalyx. Other components, including small proteoglycans and circulating proteins like albumin and orosomucoid, form the endothelial surface layer and are bound to the glycocalyx due to weak intermolecular interactions. Indeed, bound plasma albumin is a major constituent of the endothelial surface layer and contributes to its barrier function. A role for glomerular endothelial cells in the barrier of the glomerular capillary wall to protein filtration has been demonstrated by many elegant studies. However, it can only be fully understood in the context of other components, including the glomerular basement membrane, the podocytes and reabsorption of proteins by tubule epithelial cells. Discovery of the precise mechanisms that lead to glycocalyx/endothelial surface layer disruption within glomerular capillaries will hopefully lead to pharmacological interventions that specifically target this important structure.
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Affiliation(s)
| | - Jenny Nyström
- Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
| | - Börje Haraldsson
- Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
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27
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Chang YM, Liu WJ, Lee CL, Wang JS. Risk of all-cause mortality in subjects with varying degrees of renal impairment with or without dietary protein restriction. ENDOCRINOL DIAB NUTR 2021. [DOI: 10.1016/j.endinu.2021.09.009] [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: 10/19/2022]
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28
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Fotheringham AK, Solon-Biet SM, Bielefeldt-Ohmann H, McCarthy DA, McMahon AC, Ruohonen K, Li I, Sullivan MA, Whiddett RO, Borg DJ, Cogger VC, Ballard WO, Turner N, Melvin RG, Raubenheimer D, Le Couteur DG, Simpson SJ, Forbes JM. Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure. iScience 2021; 24:103308. [PMID: 34820603 PMCID: PMC8602032 DOI: 10.1016/j.isci.2021.103308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 04/29/2021] [Accepted: 10/15/2021] [Indexed: 02/06/2023] Open
Abstract
The kidneys balance many byproducts of the metabolism of dietary components. Previous studies examining dietary effects on kidney health are generally of short duration and manipulate a single macronutrient. Here, kidney function and structure were examined in C57BL/6J mice randomized to consume one of a spectrum of macronutrient combinations (protein [5%–60%], carbohydrate [20%–75%], and fat [20%–75%]) from weaning to late-middle age (15 months). Individual and interactive impacts of macronutrients on kidney health were modeled. Dietary protein had the greatest influence on kidney function, where chronic low protein intake decreased glomerular filtration rates and kidney mass, whereas it increased kidney immune infiltration and structural injury. Kidney outcomes did not align with cardiometabolic risk factors including glucose intolerance, overweight/obesity, dyslipidemia, and hypertension in mice with chronic low protein consumption. This study highlights that protein intake over a lifespan is an important determinant of kidney function independent of cardiometabolic changes.
Chronic high macronutrient intake from any source increases kidney function (GFR) Low protein intake led to greater kidney tubular structural injury and inflammation Lower protein intake decreased kidney mass and glomerular filtration capacity Kidney outcomes did not align with longevity or cardiometabolic outcomes
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Affiliation(s)
- Amelia K Fotheringham
- Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia.,Faculty of Medicine, University of Queensland, Brisbane 4067, QLD, Australia
| | - Samantha M Solon-Biet
- Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia.,School of Medical Sciences, University of Sydney, Sydney 2006, NSW, Australia
| | - Helle Bielefeldt-Ohmann
- School of Veterinary Science, University of Queensland, Gatton Campus, Gatton 4343, QLD, Australia.,School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane 4067, QLD, Australia
| | - Domenica A McCarthy
- Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia
| | - Aisling C McMahon
- Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia.,Centre for Education and Research on Aging, and Aging and Alzheimer's Institute, Concord Hospital, Sydney 2139, NSW, Australia.,ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney 2139, NSW, Australia
| | - Kari Ruohonen
- Animal Nutrition and Health, Cargill, Sandnes, Norway
| | - Isaac Li
- Faculty of Medicine, University of Queensland, Brisbane 4067, QLD, Australia
| | - Mitchell A Sullivan
- Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia
| | - Rani O Whiddett
- Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia
| | - Danielle J Borg
- Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia.,Faculty of Medicine, University of Queensland, Brisbane 4067, QLD, Australia
| | - Victoria C Cogger
- Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia.,Centre for Education and Research on Aging, and Aging and Alzheimer's Institute, Concord Hospital, Sydney 2139, NSW, Australia.,ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney 2139, NSW, Australia
| | - William O Ballard
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, NSW, Australia
| | - Nigel Turner
- Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales Sydney, NSW 2052, Australia
| | - Richard G Melvin
- Department of Biomedical Sciences, University of Minnesota Medical School, 1035 University Drive, Duluth 55812, MN, USA
| | - David Raubenheimer
- Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia.,School of Life and Environmental Sciences, University of Sydney, NSW, Australia
| | - David G Le Couteur
- Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia.,Centre for Education and Research on Aging, and Aging and Alzheimer's Institute, Concord Hospital, Sydney 2139, NSW, Australia.,ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney 2139, NSW, Australia
| | - Stephen J Simpson
- Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia.,School of Life and Environmental Sciences, University of Sydney, NSW, Australia
| | - Josephine M Forbes
- Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia.,Faculty of Medicine, University of Queensland, Brisbane 4067, QLD, Australia.,Department of Medicine, University of Melbourne, Heidelberg, VIC 3084, Australia
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29
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Mancia G, Facchetti R, Bombelli M, Cuspidi C, Grassi G. White-Coat Hypertension: Pathophysiological and Clinical Aspects: Excellence Award for Hypertension Research 2020. Hypertension 2021; 78:1677-1688. [PMID: 34757765 DOI: 10.1161/hypertensionaha.121.16489] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Few issues of modern cardiovascular medicine have been as controversial as the relationship between white-coat hypertension (WCH), that is, a common condition in which office blood pressure is elevated while out-of-office blood pressure (ambulatory blood pressure or home blood pressure) is normal. While earlier studies showed no increased risk of cardiovascular events in WCH compared with the normotensive state, more recent studies have changed this conclusion by showing that an increased cardiovascular risk represents a trait of this hypertensive phenotype. The present article will review a number of issues related to WCH, that is, its definition, pathophysiological background, clinical alterations, and prognostic significance. This will be done by considering the available evidence published during the last decades, with special focus on the data collected in PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni)-a research project performed with a cross-sectional and longitudinal design, which has provided a series of novel clinical information on WCH throughout the years. The final part of the article will discuss the therapeutic implications of the abovementioned evidence, as well as some controversial or still undefined issues related to WCH, whose investigation will be an important goal to pursue by future research.
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Affiliation(s)
- Giuseppe Mancia
- University of Milano-Bicocca (G.M.), University of Milano-Bicocca, Milan, Italy
| | - Rita Facchetti
- Clinica Medica, Department of Medicine and Surgery (R.F., M.B., C.C., G.G.), University of Milano-Bicocca, Milan, Italy
| | - Michele Bombelli
- Clinica Medica, Department of Medicine and Surgery (R.F., M.B., C.C., G.G.), University of Milano-Bicocca, Milan, Italy
| | - Cesare Cuspidi
- Clinica Medica, Department of Medicine and Surgery (R.F., M.B., C.C., G.G.), University of Milano-Bicocca, Milan, Italy
| | - Guido Grassi
- Clinica Medica, Department of Medicine and Surgery (R.F., M.B., C.C., G.G.), University of Milano-Bicocca, Milan, Italy
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30
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Mosenzon O, Wiviott SD, Heerspink HJL, Dwyer JP, Cahn A, Goodrich EL, Rozenberg A, Schechter M, Yanuv I, Murphy SA, Zelniker TA, Gause-Nilsson IAM, Langkilde AM, Fredriksson M, Johansson PA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Sabatine MS, Raz I. The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58. Diabetes Care 2021; 44:1805-1815. [PMID: 34233928 PMCID: PMC8385472 DOI: 10.2337/dc21-0076] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 05/14/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve albuminuria in patients with high cardiorenal risk. We report albuminuria change in the Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) cardiovascular outcome trial, which included populations with lower cardiorenal risk. RESEARCH DESIGN AND METHODS DECLARE-TIMI 58 randomized 17,160 patients with type 2 diabetes, creatinine clearance >60 mL/min, and either atherosclerotic cardiovascular disease (CVD; 40.6%) or risk-factors for CVD (59.4%) to dapagliflozin or placebo. Urinary albumin-to-creatinine ratio (UACR) was tested at baseline, 6 months, 12 months, and yearly thereafter. The change in UACR over time was measured as a continuous and categorical variable (≤15, >15 to <30, ≥30 to ≤300, and >300 mg/g) by treatment arm. The composite cardiorenal outcome was a ≥40% sustained decline in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage kidney disease, and cardiovascular or renal death; specific renal outcome included all except cardiovascular death. RESULTS Baseline UACR was available for 16,843 (98.15%) participants: 9,067 (53.83%) with ≤15 mg/g, 2,577 (15.30%) with >15 to <30 mg/g, 4,030 (23.93%) with 30-300 mg/g, and 1,169 (6.94%) with >300 mg/g. Measured as a continuous variable, UACR improved from baseline to 4.0 years with dapagliflozin, compared with placebo, across all UACR and eGFR categories (all P < 0.0001). Sustained confirmed ≥1 category improvement in UACR was more common in dapagliflozin versus placebo (hazard ratio 1.45 [95% CI 1.35-1.56], P < 0.0001). Cardiorenal outcome was reduced with dapagliflozin for subgroups of UACR ≥30 mg/g (P < 0.0125, P interaction = 0.033), and the renal-specific outcome was reduced for all UACR subgroups (P < 0.05, P interaction = 0.480). CONCLUSIONS In DECLARE-TIMI 58, dapagliflozin demonstrated a favorable effect on UACR and renal-specific outcome across baseline UACR categories, including patients with normal albumin excretion. The results suggest a role for SGLT2i also in the primary prevention of diabetic kidney disease.
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Affiliation(s)
- Ofri Mosenzon
- Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel .,Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Stephen D Wiviott
- TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Hiddo J L Heerspink
- University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | | | - Avivit Cahn
- Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel.,Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Erica L Goodrich
- TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Aliza Rozenberg
- Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel.,Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Meir Schechter
- Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel.,Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Ilan Yanuv
- Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel.,Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Sabina A Murphy
- TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Thomas A Zelniker
- TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | | | | | | | | | - Deepak L Bhatt
- TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Lawrence A Leiter
- Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Darren K McGuire
- Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX.,Parkland Health and Hospital System, Dallas, TX
| | - John P H Wilding
- Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, U.K
| | - Marc S Sabatine
- TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Itamar Raz
- Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel.,Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
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Guide de Pratique Clinique. Prise en charge de l’hypertension artérielle chez l’adulte en Tunisie. LA TUNISIE MÉDICALE 2021. [PMCID: PMC9003593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Ce document a été réalisé dans le cadre d'une collaboration entre l'Instance Nationale de l’Évaluation et de l'Accréditation en Santé (INEAS), la Société Tunisienne de Cardiologie et de Chirurgie Cardiovasculaire (STCCCV) et la Caisse Nationale d’Assurance Maladie (CNAM).
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32
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Molina P, Gavela E, Vizcaíno B, Huarte E, Carrero JJ. Optimizing Diet to Slow CKD Progression. Front Med (Lausanne) 2021; 8:654250. [PMID: 34249961 PMCID: PMC8267004 DOI: 10.3389/fmed.2021.654250] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 05/31/2021] [Indexed: 12/15/2022] Open
Abstract
Due to the unique role of the kidney in the metabolism of nutrients, patients with chronic kidney disease (CKD) lose the ability to excrete solutes and maintain homeostasis. Nutrient intake modifications and monitoring of nutritional status in this population becomes critical, since it can affect important health outcomes, including progression to kidney failure, quality of life, morbidity, and mortality. Although there are multiple hemodynamic and metabolic factors involved in the progression and prognosis of CKD, nutritional interventions are a central component of the care of patients with non-dialysis CKD (ND-CKD) and of the prevention of overweight and possible protein energy-wasting. Here, we review the reno-protective effects of diet in adults with ND-CKD stages 3-5, including transplant patients.
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Affiliation(s)
- Pablo Molina
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, Spain
- Department of Medicine, Universitat de València, Valencia, Spain
| | - Eva Gavela
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, Spain
| | - Belén Vizcaíno
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, Spain
| | - Emma Huarte
- Department of Nephrology, Hospital San Pedro, Logroño, Spain
| | - Juan Jesús Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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33
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Summarizing the Effective Herbs for the Treatment of Hypertensive Nephropathy by Complex Network and Machine Learning. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5590743. [PMID: 34194519 PMCID: PMC8214481 DOI: 10.1155/2021/5590743] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 05/04/2021] [Accepted: 06/03/2021] [Indexed: 12/13/2022]
Abstract
Hypertensive nephropathy is a common complication of hypertension. Traditional Chinese medicine has been used in the clinical treatment of hypertensive nephropathy for a long time, but the commonly used prescriptions have not been summarized, and the basic therapeutic approaches have not been discussed. Based on data from 3 years of electronic medical records of traditional Chinese medicine used at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, a complex network and machine learning algorithm was used to explore the prescribed herbs of traditional Chinese medicine in the treatment of hypertensive nephropathy (HN). In this study, complex network algorithms were used to describe traditional Chinese medicine prescriptions for HN treatment. The Apriori algorithm was used to analyze the compatibility of these treatments with modern medicine. Data on the targets and regulatory genes related to hypertensive nephropathy and the herbs that affect their expression were obtained from public databases, and then, the signaling pathways enriched with these genes were identified on the basis of their participation in biological processes. A clustering algorithm was used to analyze the therapeutic pathways at multiple levels. A total of 1499 prescriptions of traditional Chinese medicines used for the treatment of hypertensive renal damage were identified. Fourteen herbs used to treat hypertensive nephropathy act through different biological pathways: huangqi, danshen, dangshen, fuling, baizhu, danggui, chenpi, banxia, gancao, qumai, cheqianzi, ezhu, qianshi, and niuxi. We found the formulae of these herbs and observed that they could downregulate the expression of inflammatory cytokines such as TNF, IL1B, and IL6 and the NF-κB and MAPK signaling pathways to reduce the renal inflammatory damage caused by excessive activation of RAAS. In addition, these herbs could facilitate the deceleration in the decline of renal function and relieve the symptoms of hypertensive nephropathy. In this study, the traditional Chinese medicine approach for treating hypertensive renal damage is summarized and effective treatment prescriptions were identified and analyzed. Data mining technology provided a feasible method for the collation and extraction of traditional Chinese medicine prescription data and provided an objective and reliable tool for use in determining the TCM treatments of hypertensive nephropathy.
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34
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Persson F, Bain SC, Mosenzon O, Heerspink HJL, Mann JFE, Pratley R, Raz I, Idorn T, Rasmussen S, von Scholten BJ, Rossing P. Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial. Diabetes Care 2021; 44:1020-1026. [PMID: 33504496 PMCID: PMC7985419 DOI: 10.2337/dc20-1622] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 01/02/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE A post hoc analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events. RESEARCH DESIGN AND METHODS LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5-5 years in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with >30% reduction (n = 2,928), 30-0% reduction (n = 1,218), or any increase in UACR (n = 4,124), irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [<30 mg/g, 30-300 mg/g, or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes. RESULTS For MACE, hazard ratios (HRs) for those with >30% and 30-0% UACR reduction were 0.82 (95% CI 0.71, 0.94; P = 0.006) and 0.99 (0.82, 1.19; P = 0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs were 0.67 (0.49, 0.93; P = 0.02) and 0.97 (0.66, 1.43; P = 0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in >30% reduction subgroups with baseline micro- or macroalbuminuria. CONCLUSIONS A reduction in albuminuria during the 1st year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential.
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Affiliation(s)
| | - Stephen C Bain
- Diabetes Research Unit Cymru, Swansea University Medical School, Swansea, U.K
| | - Ofri Mosenzon
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.,Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel
| | - Hiddo J L Heerspink
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Johannes F E Mann
- KfH Kidney Center, Munich, and Friedrich Alexander University, Erlangen, Germany
| | | | - Itamar Raz
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
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35
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Lin M, Heizati M, Wang L, Nurula M, Yang Z, Wang Z, Abudoyreyimu R, Wu Z, Li N. A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes. Blood Press 2021; 30:145-153. [PMID: 33682538 DOI: 10.1080/08037051.2021.1880881] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
PURPOSE Hypertension commonly co-exists with diabetes mellitus (DM), and both are closely related to adverse health outcomes. The activation of aldosterone and mineralocorticoid receptor (MR) may play important roles in this process. Therefore, we aim to evaluate the efficacy of MR antagonists on cardiovascular risk factors, including blood pressure (BP), glucose, lipids, renal function, fibrosis and inflammatory and its safety in patients with both hypertension and DM. METHODS We searched PubMed, Embase, Web of Science and Cochrane databases for clinical trials published until December 31, 2019. Studies comparing the effect of spironolactone to placebo in patients with hypertension and DM were included. Mean difference with 95% confidence intervals was used to report outcomes. RESULTS Eleven randomised placebo-controlled trials with 640 participants were finally included with mean follow-up of 5 months. Compared to placebo, spironolactone significantly reduced office systolic (-6.57, 95%CI: -9.21, -3.93) and diastolic BP (-2.63, 95%CI: -4.25, -1.02) as well as ambulatory BP; increased glycosylated haemoglobin by 0.3 but no clear effect on fasting glucose. Spironolactone induced a significantly reduction of urinary albumin but increased serum creatinine (7.60, 95%CI: 4.94, 10.27) and decreased glomerular filtration rate (-4.28, 95%CI: -6.38, -2.18). Markers of fibrosis and inflammation, including NIIINP, PICP, hs-CRP and TNF-α were also decreased after spironolactone therapy. For lipid metabolism, there was no significant difference between groups. Spironolactone mildly increased serum potassium (0.30, 95%CI: 0.23, 0.37). 2.5% subjects treated with spironolactone experienced mild to moderate hyperkalaemia and received medication or dietary advice and another 1.6% developed severe hyperkalaemia and withdrawn from the studies. CONCLUSION Spironolactone reduced BP and urinary albumin, improve fibrosis and inflammation, whereas slightly increases the glycosylated haemoglobin and serum creatinine in patients with hypertension and diabetes. Long-term RCTs to assess the effects of spironolactone on cardiovascular events in this population are warranted.
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Affiliation(s)
- Mengyue Lin
- Xinjiang Medical University, Urumqi, China.,Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.,Xinjiang Hypertension Institute, Urumqi, China.,National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, China
| | - Mulalibike Heizati
- Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.,Xinjiang Hypertension Institute, Urumqi, China.,National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, China
| | - Lin Wang
- Xinjiang Medical University, Urumqi, China.,Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.,Xinjiang Hypertension Institute, Urumqi, China.,National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, China
| | - Muyesaier Nurula
- Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.,Xinjiang Hypertension Institute, Urumqi, China.,National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, China
| | - Zhikang Yang
- Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.,Xinjiang Hypertension Institute, Urumqi, China.,National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, China
| | - Zhongrong Wang
- Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.,Xinjiang Hypertension Institute, Urumqi, China.,National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, China
| | - Reyila Abudoyreyimu
- Xinjiang Medical University, Urumqi, China.,Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.,Xinjiang Hypertension Institute, Urumqi, China.,National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, China
| | - Zihao Wu
- Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.,Xinjiang Hypertension Institute, Urumqi, China.,National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, China
| | - Nanfang Li
- Xinjiang Medical University, Urumqi, China.,Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.,Xinjiang Hypertension Institute, Urumqi, China.,National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, China
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36
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Renal outcomes and blood pressure patterns in diabetic and nondiabetic individuals at high cardiovascular risk. J Hypertens 2021; 39:766-774. [PMID: 33560052 DOI: 10.1097/hjh.0000000000002697] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Diabetes and hypertension are risk factors for renal and cardiovascular outcomes. Data on the association of achieved blood pressure (BP) with renal outcomes in patients with and without diabetes are sparse. We investigated the association of achieved SBP, DBP with renal outcomes and urinary albumin excretion (UAE) in people with vascular disease. METHODS In this pooled analysis, we assessed renal outcome data from high-risk patients aged 55 years or older with a history of cardiovascular disease, 70% of whom had hypertension, randomized to The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and to Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease trials investigating telmisartan, ramipril and their combination with a median follow-up of 56 months. Standardized office BP was measured every 6 months, estimated glomerular filtration rate (eGFR) and UAE at baseline, 2 years and study end. Associations of mean achieved BP on treatment were investigated on major renal outcomes including end-stage renal disease (ESRD), decline of eGFR by at least 40%, doubling of creatinine and the composites thereof and on UAE. Analyses were by Cox regression analysis, analysis of variance and Chi2-test. Of 30 937 patients with complete data, 19 450 patients without and 11 487 with diabetes were enrolled between 1 December 2001 and 31 July 2003 and followed until 31 July 2008. Data were pooled as the outcomes for telmisartan 80 mg/day (n = 2903) or placebo (n = 2907) for Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease and ramipril 10 mg/day (n = 8407), telmisartan 80 mg/day (n = 8386) or the combination of both (n = 8334) were similar. RESULTS For both those with and without diabetes, the hazard ratios for the composites ESRD or doubling of serum creatinine (707 events overall) and ESRD or 40% eGFR loss (2371 events overall) reached a nadir at achieved SBP of 120 to less than 140 mmHg, and increased with higher and lower SBP with similar relative risk with or without diabetes. For example, risk for the former composite reached a hazard ratios 3.06 (confidence interval 1.90-4.92) with a mean achieved SBP more than 160 mmHg compared with 120 to less than 130 mmHg with diabetes and hazard ratios 2.14 (1.09-4.26) without diabetes. In contrast, the development of new microalbuminuria and macroalbuminuria (3002 and 846 events overall) associated linearly over the whole range of achieved SBP (apart from a slight increase in risk at SBP less than 120 mmHg only in those without diabetes). Absolute risks for the composite and albuminuria outcomes were consistently greater in those with diabetes as compared with without diabetes with high event rates over the whole SBP spectrum. The increased renal risk at low SBP was not related to a meaningful reduction of mandated study drugs or open label renin-angiotensin-aldosterone system inhibition. CONCLUSION In patients at high cardiovascular risk, SBP levels more than 140 mmHg and less than 120 are associated with increased risk for renal outcomes. Renal risk was greater in diabetes across the whole range of achieved SBP and DBP. These data suggest similar target BP range in patients with and without diabetes to prevent renal outcomes, a frequent complication in high-risk vascular patients. CLINICAL TRIAL REGISTRATION Clinical Trial registration: http://clinicaltrials.gov.Unique identifier: NCT00153101.
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37
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Olsen E, Holzhauer B, Julius S, Kjeldsen SE, Larstorp ACK, Mancia G, Mehlum MH, Mo R, Rostrup M, Søraas CL, Zappe D, Weber MA. Cardiovascular outcomes at recommended blood pressure targets in middle-aged and elderly patients with type 2 diabetes mellitus compared to all middle-aged and elderly hypertensive study patients with high cardiovascular risk. Blood Press 2021; 30:90-97. [PMID: 33403890 DOI: 10.1080/08037051.2020.1856642] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
PURPOSE Event-based clinical outcome trials have shown limited evidence to support guidelines recommendations to lower blood pressure (BP) to <130/80 mmHg in middle-aged and elderly hypertensive patients with diabetes mellitus or with general high cardiovascular (CV) risk. We addressed this issue by post-hoc analysing the risk of CV events in patients who participated in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and compared the hypertensive patients with type 2 diabetes mellitus with all high-risk hypertensive patients. MATERIALS AND METHODS Patients were divided into 4 groups according to the proportion of on-treatment visits before the occurrence of an event (<25% to ≥75%) in which BP was reduced to <140/90 or <130/80 mmHg. Patients with diabetes mellitus (n = 5250) were compared with the entire VALUE population with high CV risk (n = 15,245). RESULTS After adjustments for baseline differences between groups, a reduction in the proportion of visits in which BP was reduced to <140/90 mmHg, but not to <130/80 mmHg, was accompanied by a progressive increase in the risk of CV morbidity and mortality as well as stroke, myocardial infarction and heart failure in both diabetes mellitus and in all high-risk patients. Target BP <130/80 mmHg reduced stroke risk in the main population but not in the diabetes mellitus patients. Patients with diabetes mellitus had higher event rates for the primary cardiac endpoint and all-cause mortality driven by a higher rate of heart failure. CONCLUSION In the high-risk hypertensive patients of the VALUE trial achieving more frequently BP <140/90 mmHg, but not <130/80 mmHg, showed principally the same protective effect on overall and cause-specific cardiovascular outcomes in patients with diabetes mellitus and in the general high-risk hypertensive population.
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Affiliation(s)
- Eirik Olsen
- Department of Cardiology, St. Olav's Hospital, and University of Trondheim, Trondheim, Norway
| | | | - Stevo Julius
- Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Sverre E Kjeldsen
- Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.,Departments of Cardiology and Nephrology, Oslo University Hospital, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Cardiovascular & Renal Research Center, Oslo University Hospital, Oslo, Norway
| | - Anne Cecilie K Larstorp
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Cardiovascular & Renal Research Center, Oslo University Hospital, Oslo, Norway.,Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
| | | | - Maria H Mehlum
- Department of Geriatrics, Oslo University Hospital, Oslo, Norway
| | - Rune Mo
- Department of Cardiology, St. Olav's Hospital, and University of Trondheim, Trondheim, Norway
| | - Morten Rostrup
- Cardiovascular & Renal Research Center, Oslo University Hospital, Oslo, Norway.,Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.,Department of Behavioural Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Camilla L Søraas
- Cardiovascular & Renal Research Center, Oslo University Hospital, Oslo, Norway.,Unit of Environmental and Occupational Medicine, Oslo University Hospital, Oslo, Norway
| | | | - Michael A Weber
- Department of Cardiovascular Medicine, State University of New York, Downstate College of Medicine, NY, USA
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Cosimato C, Agoritsas T, Mavrakanas TA. Mineralocorticoid receptor antagonists in patients with chronic kidney disease. Pharmacol Ther 2020; 219:107701. [PMID: 33027644 DOI: 10.1016/j.pharmthera.2020.107701] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 09/17/2020] [Indexed: 11/24/2022]
Abstract
Mineralocorticoid receptor antagonists (MRA) can reduce cardiovascular morbidity and mortality in patients with heart failure and ischemic heart disease. In addition, these agents have been used in patients with diabetic nephropathy to control proteinuria and slow down chronic kidney disease (CKD) progression. Current guidelines recommend against the use of MRAs in patients with advanced CKD. However, there is growing interest on their use in this population that has unmet needs (high cardiovascular morbidity and mortality) and unique challenges (risk of acute kidney injury or hyperkalemia). This narrative review discusses the emerging role of MRAs for the management of cardiovascular disease and/or the prevention of CKD progression, highlighting results from randomized controlled trials and presenting real-world data from available registries. Results from recent trials in patients on maintenance dialysis are also discussed.
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Affiliation(s)
- Cosimo Cosimato
- Division of General Internal Medicine, Department of Medicine, University Hospitals of Geneva & Faculty of Medicine, Geneva, Switzerland
| | - Thomas Agoritsas
- Division of General Internal Medicine, Department of Medicine, University Hospitals of Geneva & Faculty of Medicine, Geneva, Switzerland; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Thomas A Mavrakanas
- Division of General Internal Medicine, Department of Medicine, University Hospitals of Geneva & Faculty of Medicine, Geneva, Switzerland; Division of Nephrology, Department of Medicine, McGill University, Montreal, Quebec, Canada.
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39
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Abstract
Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease in the United States. Approximately 30% to 40% of individuals with diabetes mellitus develop DKD, and the presence of DKD significantly elevates the risk for morbidity and mortality. Understanding of DKD has grown in recent years. This review describes the pathogenesis of DKD and expands on evidence-based strategies for DKD management, integrating traditional approaches for hyperglycemia, hypertension, and albuminuria management with emerging therapeutic options. Given the public health burden of DKD, it is essential to prioritize prevention, recognition, and management of DKD in the primary care setting.
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40
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Thethi TK, Pratley R, Meier JJ. Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. Diabetes Obes Metab 2020; 22:1263-1277. [PMID: 32267058 PMCID: PMC7384149 DOI: 10.1111/dom.14054] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 03/27/2020] [Accepted: 04/05/2020] [Indexed: 01/02/2023]
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended for glycaemic management in patients with type 2 diabetes (T2D). Oral semaglutide, the first oral GLP-1RA, has recently been approved for clinical use, based on the results of the randomized, Phase 3a Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) clinical trials. The PIONEER programme tested oral semaglutide in patients with T2D of duration ranging from 3.5 to 15 years, from monotherapy through to insulin add-on, in global populations and two trials dedicated to Japanese patients. Outcomes (glycated haemoglobin [HbA1c] and body weight reduction, plus other relevant efficacy and safety endpoints) were tested against both placebo and active standard-of-care medications. A separate trial evaluated the cardiovascular safety of oral semaglutide in patients with T2D at high cardiovascular risk. Over periods of treatment up to 78 weeks, oral semaglutide 7 and 14 mg once daily reduced HbA1c and body weight across the spectrum of T2D, and improved other diabetes-related endpoints, such as fasting plasma glucose. Oral semaglutide provided significantly better efficacy than placebo and commonly used glucose-lowering medications from the dipeptidyl peptidase-4 inhibitor (sitagliptin) and sodium-glucose co-transporter-2 inhibitor (empagliflozin) classes, as well as the subcutaneous GLP-1RAs liraglutide and dulaglutide. Oral semaglutide was well tolerated in line with the known safety profile of GLP-1RAs, with transient gastrointestinal events being the most common side effects reported. Cardiovascular safety was demonstrated for oral semaglutide in patients with cardiovascular disease or high cardiovascular risk. The results of the PIONEER programme suggest that oral semaglutide is efficacious and well tolerated for glycaemic control of T2D. The availability of oral semaglutide may help to broaden treatment choice and facilitate adoption of earlier GLP-1RA treatment in the paradigm of T2D management.
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Affiliation(s)
- Tina K. Thethi
- AdventHealth Translational Research InstituteOrlandoFloridaUSA
| | - Richard Pratley
- AdventHealth Translational Research InstituteOrlandoFloridaUSA
| | - Juris J. Meier
- Diabetes Centre Bochum‐Hattingen, St Josef‐HospitalRuhr‐University BochumBochumGermany
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41
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Muzurović E, Mikhailidis DP. Impact of glucagon-like peptide 1 receptor agonists and sodium-glucose transport protein 2 inhibitors on blood pressure and lipid profile. Expert Opin Pharmacother 2020; 21:2125-2135. [DOI: 10.1080/14656566.2020.1795132] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Emir Muzurović
- Department of Internal Medicine, Endocrinology Section, Clinical Center of Montenegro, Podgorica, Montenegro
- University of Montenegro Faculty of Medicine, Podgorica, Montenegro
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK
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Yang CW, Guo YC, Li CI, Liu CS, Lin CH, Liu CH, Wang MC, Yang SY, Li TC, Lin CC. Subclinical Atherosclerosis Markers of Carotid Intima-Media Thickness, Carotid Plaques, Carotid Stenosis, and Mortality in Community-Dwelling Adults. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17134745. [PMID: 32630321 PMCID: PMC7369727 DOI: 10.3390/ijerph17134745] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/24/2020] [Accepted: 06/29/2020] [Indexed: 12/21/2022]
Abstract
Carotid intima–media thickness (IMT), plaque, and stenosis are widely used as early surrogate markers of subclinical atherosclerosis and strong predictors of future deaths and cardiovascular events. Albuminuria is an indicator of generalized endothelial dysfunction that speeds up atherosclerosis. However, previous studies reporting these associations cannot rule out the confounding effect of albuminuria. We aimed to examine the independent and joint relationships between IMT markers and 10-year mortality in community-dwelling Taiwanese adults. This work was a community-based prospective cohort study consisting of 2956 adults aged at least 30 years recruited in 2007 and followed up through 2019. Cox proportional hazard regression models were used to examine associations of these subclinical atherosclerosis markers with mortality. During an average of 9.41 years of follow up, 242 deaths occurred. The mortality rate was 8.70 per 1000 person-years. Compared with those with carotid IMT less than 1.0 mm, persons with severely increased carotid IMT (≥2.0 mm) had an increased risk for death (hazard ratio (HR): 1.79; 95% confidence interval (CI): 1.07, 3.00). Compared with those without carotid plaque, persons with carotid plaque were more likely to have an increased risk for death (1.65; 1.21–2.32). Compared with those with carotid stenosis less than 25%, persons with carotid stenosis of 25–36% had a significant increased risk for death (1.57; 1.12–2.22). Considering these three IMT markers along with the traditional risk factors (c-statistic: 0.85) significantly increased their predictive ability of mortality compared with any individual variable’s predictive ability (all p-values < 0.001 for comparisons of c-statistic values). Carotid IMT measures, including IMT thickness, carotid plaque, and carotid stenosis were significant independent predictors of mortality. Our study supports evidence of blood pressure-related media thickening markers to assess future mortality risks in Chinese adults of general population.
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Affiliation(s)
- Chuan-Wei Yang
- Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan; (C.-W.Y.); (C.-I.L.)
| | - Yuh-Cherng Guo
- Department of Neurology, China Medical University Hospital, Taichung 404, Taiwan; (Y.-C.G.); (C.-H.L.)
- School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan; (C.-S.L.); (C.-H.L.); (M.-C.W.)
| | - Chia-Ing Li
- Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan; (C.-W.Y.); (C.-I.L.)
- School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan; (C.-S.L.); (C.-H.L.); (M.-C.W.)
| | - Chiu-Shong Liu
- School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan; (C.-S.L.); (C.-H.L.); (M.-C.W.)
- Department of Family Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - Chih-Hsueh Lin
- School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan; (C.-S.L.); (C.-H.L.); (M.-C.W.)
- Department of Family Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - Chung-Hsiang Liu
- Department of Neurology, China Medical University Hospital, Taichung 404, Taiwan; (Y.-C.G.); (C.-H.L.)
| | - Mu-Cyun Wang
- School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan; (C.-S.L.); (C.-H.L.); (M.-C.W.)
- Department of Family Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - Shing-Yu Yang
- Department of Public Health, College of Public Health, China Medical University, Taichung 404, Taiwan;
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung 404, Taiwan;
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung 404, Taiwan
- Correspondence: (T.-C.L.); (C.-C.L.); Tel.: +886-4-2205-3366 (ext. 6605); Fax: 886-4-2207-8539
| | - Cheng-Chieh Lin
- School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan; (C.-S.L.); (C.-H.L.); (M.-C.W.)
- Department of Family Medicine, China Medical University Hospital, Taichung 404, Taiwan
- Correspondence: (T.-C.L.); (C.-C.L.); Tel.: +886-4-2205-3366 (ext. 6605); Fax: 886-4-2207-8539
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Semicarbazide-sensitive amine oxidase inhibition ameliorates albuminuria and glomerulosclerosis but does not improve tubulointerstitial fibrosis in diabetic nephropathy. PLoS One 2020; 15:e0234617. [PMID: 32555665 PMCID: PMC7302447 DOI: 10.1371/journal.pone.0234617] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 05/29/2020] [Indexed: 11/19/2022] Open
Abstract
Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme with a unique dual function in controlling inflammation as well as reactive oxygen species (ROS) generation. We have demonstrated benefit of SSAO inhibition in acute kidney fibrosis. However the function of SSAO in chronic kidney disease (CKD) and diabetic kidney disease (DKD) is yet to be determined. We aimed to assess the effectiveness of a SSAO inhibitor (SSAOi; PXS-4728A) as an antifibrotic agent using a diabetic model of CKD. Diabetic mice were treated with SSAOi for 24 weeks and outcomes compared with untreated diabetic mice and telmisartan treated animals as a standard of care comparator. Extracellular matrix markers, fibronectin and oxidative stress, were downregulated in diabetic mice treated with SSAOi compared with untreated diabetic mice. Expression of the pan-leukocyte marker CD45 was also supressed by SSAOi. SSAO inhibition in diabetic mice resulted in a significant reduction in glomerulosclerosis and associated albuminuria compared to untreated diabetic mice. However, the effect of SSAO inhibition was less obvious in the tubulointerstitial compartment than in the glomeruli. Therefore, SSAO may be a potential target for diabetic glomerulosclerosis.
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Gianesello L, Del Prete D, Ceol M, Priante G, Calò LA, Anglani F. From protein uptake to Dent disease: An overview of the CLCN5 gene. Gene 2020; 747:144662. [PMID: 32289351 DOI: 10.1016/j.gene.2020.144662] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 04/07/2020] [Indexed: 12/12/2022]
Abstract
Proteinuria is a well-known risk factor, not only for renal disorders, but also for several other problems such as cardiovascular diseases and overall mortality. In the kidney, the chloride channel Cl-/H+ exchanger ClC-5 encoded by the CLCN5 gene is actively involved in preventing protein loss. This action becomes evident in patients suffering from the rare proximal tubulopathy Dent disease because they carry a defective ClC-5 due to CLCN5 mutations. In fact, proteinuria is the distinctive clinical sign of Dent disease, and mainly involves the loss of low-molecular-weight proteins. The identification of CLCN5 disease-causing mutations has greatly improved our understanding of ClC-5 function and of the ClC-5-related physiological processes in the kidney. This review outlines current knowledge regarding the CLCN5 gene and its protein product, providing an update on ClC-5 function in tubular and glomerular cells, and focusing on its relationship with proteinuria and Dent disease.
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Affiliation(s)
- Lisa Gianesello
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy.
| | - Dorella Del Prete
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy.
| | - Monica Ceol
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy.
| | - Giovanna Priante
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy.
| | - Lorenzo Arcangelo Calò
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy.
| | - Franca Anglani
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy.
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Álvarez-Aliaga A, Frómeta-Guerra A, Suárez-Quesada A, Del Llano-Sosa D, Berdú-Saumell J, Lago-Santiesteban YA. Prognostic model of the adaptive changes from hypertensive cardiopathy: from mild diastolic dysfunction to depressed systolic function. Medwave 2020; 20:e7873. [PMID: 32469849 DOI: 10.5867/medwave.2020.03.7873] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 03/18/2020] [Indexed: 11/27/2022] Open
Abstract
Introduction By definition, hypertensive cardiopathy is a series of complex and variable effects responsible for the chronic elevation of blood pressure in the heart. It stands out within a broad spectrum of cardiovascular diseases associated with hypertension. Objective To evaluate the capacity to predict the development of adaptive changes to hypertensive cardiopathy within ten years following diagnosis of the condition, using a model based on prognostic factors. Methods A prospective cohort study was conducted in hypertensive patients. The patients were followed at the specialized hypertension physicians office of the specialty policlinic attached to Carlos Manuel de Céspedes University Hospital, in the Bayamo Municipality, Granma Province, Cuba, from 1 January 2008 to 31 December 2018. Results Coxs proportional regression model showed a significant statistical relationship between most of the factors and the development of the adaptive changes in hypertensive cardiopathy within ten years of follow-up after the diagnosis of this condition. The lack of blood pressure control (Hazard ratio: 2.090; confidence interval 95%: 1.688 to 2.588; p: 0.000) followed by stage 2 of hypertension (hazard ratio: 1.987; confidence interval 95%: 1.584 to 2.491; p: 0.000) were the main factors. Internal validation of the model, discriminant capacity (C- statistic: 0.897) and calibration Hosmer-Lemeshow (χ2: 5.384; p: 0.716), was acceptable. Conclusions We develop a model to predict the progression of hypertensive cardiopathy from grade I to grade IV with adequate discriminatory capacity. The model is based on prognostic factors, among which characteristic effects of arterial hypertension, diabetes mellitus, and chronic kidney disease stood out.
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Affiliation(s)
- Alexis Álvarez-Aliaga
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. . ORCID: 0000-0002-4706-3821
| | - Adonis Frómeta-Guerra
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0003-0436-5974
| | - Alexis Suárez-Quesada
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0002-7672-5601
| | - David Del Llano-Sosa
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0002-0104-1715
| | - Joel Berdú-Saumell
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0002-8818-2704
| | - Yasel Alberto Lago-Santiesteban
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0003-2933-0663
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Chung YR, Kim YH, Byeon HE, Jo DH, Kim JH, Lee K. Effect of a Single Intravitreal Bevacizumab Injection on Proteinuria in Patients With Diabetes. Transl Vis Sci Technol 2020; 9:4. [PMID: 32818092 PMCID: PMC7396195 DOI: 10.1167/tvst.9.4.4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 12/09/2019] [Indexed: 01/02/2023] Open
Abstract
Purpose Proteinuria is the second most common complication after hypertension after systemic administration of bevacizumab. Therefore we aimed to analyze the effect of intravitreal bevacizumab (IVB) injection on proteinuria in patients with diabetes. Methods Patients scheduled to receive IVB injection from May 1, 2018, to December 31, 2018, were prospectively enrolled. In total, 53 patients with diabetes (26 with nonproliferative diabetic retinopathy and 27 with proliferative diabetic retinopathy) and 37 patients without diabetes were included. Urine tests were performed within 1 month of and 7 ± 1 days after IVB injection. Urinary protein, creatinine, and albumin concentrations were quantitatively measured, and urinary protein-to-creatinine ratio and urinary albumin-to-creatinine ratio (UACR) were calculated from these data before and after IVB injection. Results The mean urinary microalbumin concentrations and urinary protein-to-creatinine ratio were significantly higher in patients with diabetes, both before and after IVB injection. There were no differences between patients with nonproliferative diabetic retinopathy and proliferative diabetic retinopathy. About 80% of patients with diabetes showed improved albuminuria or at least no harmful effect in terms of albuminuria. Patients with deteriorated baseline UACR showed more residual increase in UACR after IVB injection (P < 0.05 in all groups). Conclusions Close monitoring of renal function after IVB might be needed in patients with diabetes according to the severity of nephropathy. Translational Relevance Our results may provide information regarding the renal function of IVB-treated patients with diabetes.
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Affiliation(s)
- Yoo-Ri Chung
- Department of Ophthalmology, Ajou University School of Medicine, Suwon, Korea
| | - Young Ho Kim
- Department of Ophthalmology, Ajou University School of Medicine, Suwon, Korea
| | - Hye-Eun Byeon
- Institute of Medical Science, Ajou University School of Medicine, Suwon, Korea
| | - Dong Hyun Jo
- Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
| | - Jeong Hun Kim
- Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.,Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.,Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea
| | - Kihwang Lee
- Department of Ophthalmology, Ajou University School of Medicine, Suwon, Korea
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Planchais M, Brilland B, Demiselle J, Besson V, Duveau A, Croué A, Cousin M, Subra JF, Augusto JF, Garnier AS. Renal biopsy in very elderly patients (over 80 years): clinical presentation, histological diagnosis, and long-term outcome. Int Urol Nephrol 2020; 52:721-729. [PMID: 32114671 DOI: 10.1007/s11255-020-02403-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 02/03/2020] [Indexed: 10/24/2022]
Abstract
PURPOSE Data regarding the long-term outcome of very elderly (VE) patients undergoing renal biopsy (RB) are lacking. The objective of this study was to analyse the outcome of VE patients undergoing RB. METHODS All patients over 65 years that underwent native RB between 2004 and 2016 in our center were included. Among the 206 included patients, those over 80 years (VE, 46 patients) were analysed and compared to those aged 65-80 years (160 patients). The outcomes of the VE group were analysed. RESULTS Baseline characteristics, renal presentation, safety of RB and RB-related diagnosis were not different between VE patients and 65-80-year-old patients. Survival of VE patients was 73.1, 50.6 and 21.8% at 2, 4 and 6 years after RB, significantly poorer than those of 65-80-year-old group. Early death (< 1 year) occurred in 10 VE patients, was associated with a higher proteinuria-to-creatininuria ratio and tended to be associated with a more frequent dialysis need at RB. Of the 46 VE patients, 31 (67.4%) were diagnosed with a potentially reversible kidney disease, of whom 17 (40%) were started on immunosuppressive regimens. Survival of patients with a reversible kidney disease tended to be better than those with other diseases. CONCLUSION RB appears as a safe and valuable procedure to assess diagnosis of kidney disease in VE patients. Our data suggest that RB is critical for the identification and treatment decision of patients with potentially reversible diseases and may translate in clinical improvement.
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Affiliation(s)
- Martin Planchais
- CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université Angers, 4 rue Larrey, 49933, Angers Cedex 9, France
| | - Benoit Brilland
- CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université Angers, 4 rue Larrey, 49933, Angers Cedex 9, France.,CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France
| | - Julien Demiselle
- CHU Angers, Département de Réanimation Médicale et Médecine Hyperbare, Université Angers, Angers, France
| | - Virginie Besson
- CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université Angers, 4 rue Larrey, 49933, Angers Cedex 9, France
| | - Agnès Duveau
- CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université Angers, 4 rue Larrey, 49933, Angers Cedex 9, France
| | - Anne Croué
- CHU Angers, Département de Pathologie cellulaire et tissulaire, Université Angers, Angers, France
| | - Maud Cousin
- CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université Angers, 4 rue Larrey, 49933, Angers Cedex 9, France
| | - Jean-François Subra
- CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université Angers, 4 rue Larrey, 49933, Angers Cedex 9, France.,CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France
| | - Jean-François Augusto
- CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université Angers, 4 rue Larrey, 49933, Angers Cedex 9, France.,CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France
| | - Anne-Sophie Garnier
- CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université Angers, 4 rue Larrey, 49933, Angers Cedex 9, France.
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Ceol M, Gianesello L, Tosetto E, Priante G, Del Prete D, Anglani F. CLCN5 5'UTR isoforms in human kidneys: differential expression analysis between controls and patients with glomerulonephritis. J Investig Med 2020; 68:864-869. [PMID: 32019767 DOI: 10.1136/jim-2019-001205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/03/2020] [Indexed: 12/24/2022]
Abstract
ClC-5, the electrogenic chloride/proton exchanger strongly expressed in renal proximal tubules, belongs to the endocytic macromolecular complex responsible for albumin and low-molecular-weight protein uptake. ClC-5 was found to be overexpressed in glomeruli of glomerulonephritis and in cultured human podocytes under albumin overload. The transcriptional regulation of human ClC-5 is not fully understood. Three functional promoters of various strengths and 11 different 5' untranslated region (5'UTR) isoforms of CLCN5 messenger RNA (mRNA) were detected in the human kidney (variants 1-11). The aim of this study was to investigate the expression pattern of CLCN5 5'UTR variants and the CLCN5 common translated region in glomerulonephritis. The 5'UTR ends and the translated region of CLCN5 mRNA were analyzed using quantitative relative real-time PCR or quantitative comparative endpoint PCR with GAPDH as housekeeping gene in 8 normal kidneys and 12 renal biopsies from patients with glomerulonephritis. The expression profile for all variants in normal and glomerulonephritis biopsies was similar, and variant 3 and alternative variant 4 were the most abundantly expressed in both sets. In glomerulonephritis biopsies, isoforms under the control of a weak promoter (variants 4, 6 and 7) showed an increased expression leading to an increase in the CLCN5 translated region, underscoring their importance in kidney pathophysiology. Since weak promoters can be turned on by different stimuli, these data support the hypothesis that proteinuria could be one of the stimuli capable of starting a signaling pathway that induces an increase in CLCN5 transcription.
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Affiliation(s)
- Monica Ceol
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Lisa Gianesello
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Enrica Tosetto
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Giovanna Priante
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Dorella Del Prete
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Franca Anglani
- Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy
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Nakada Y, Onoue K, Nakano T, Ishihara S, Kumazawa T, Nakagawa H, Ueda T, Nishida T, Soeda T, Okayama S, Watanabe M, Kawakami R, Saito Y. AST-120, an Oral Carbon Absorbent, Protects against the Progression of Atherosclerosis in a Mouse Chronic Renal Failure Model by Preserving sFlt-1 Expression Levels. Sci Rep 2019; 9:15571. [PMID: 31666542 PMCID: PMC6821698 DOI: 10.1038/s41598-019-51292-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 09/27/2019] [Indexed: 12/21/2022] Open
Abstract
Soluble Flt-1 (sFlt-1), an endogenous antagonist of the proatherogenic cytokine placental growth factor, is decreased in chronic kidney disease (CKD), leading to atherosclerotic progression. In this study, we investigated the effect of AST-120, an oral carbon adsorbent which can remove uremic toxins, on sFlt-1 expression levels and atherosclerosis progression. Atherosclerotic apolipoprotein E-deficient mice underwent a 5/6 nephrectomy (5/6 NR) or a sham operation (sham) at 8 weeks of age and were then treated or not with oral AST-120 for 12 weeks. sFlt-1 expression levels and the degree of atherosclerosis were assessed at 22 weeks of age in each of the four groups (sham; n = 7, 5/6 NR; n = 10, sham + AST-120: n = 8, 5/6 NR + AST-120; n = 8). The expression levels of sFlt-1 mRNA in the kidney were significantly lower in the 5/6 NR group than in the sham group, but AST-120 treatment prevented this decrease in sFlt-1 levels. Similarly, the atherosclerotic plaque area of the thoracoabdominal aorta was significantly larger in the 5/6 NR group than in the sham group, and AST-120 treatment prevented this increase in atherosclerosis. AST-120 could, therefore, be used as a therapeutic to treat atherosclerosis in patients with CKD.
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Affiliation(s)
- Yasuki Nakada
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Kenji Onoue
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan.
| | - Tomoya Nakano
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Satomi Ishihara
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Takuya Kumazawa
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Hitoshi Nakagawa
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Tomoya Ueda
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Taku Nishida
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Tsunenari Soeda
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Satoshi Okayama
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Makoto Watanabe
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Rika Kawakami
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Yoshihiko Saito
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan
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Márquez DF, Ruiz-Hurtado G, Segura J, Ruilope L. Microalbuminuria and cardiorenal risk: old and new evidence in different populations. F1000Res 2019; 8. [PMID: 31583081 PMCID: PMC6758838 DOI: 10.12688/f1000research.17212.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/30/2019] [Indexed: 01/13/2023] Open
Abstract
Since the association of microalbuminuria (MAU) with cardiovascular (CV) risk was described, a huge number of reports have emerged. MAU is a specific integrated marker of CV risk and targets organ damage in patients with hypertension, chronic kidney disease (CKD), and diabetes and its recognition is important for identifying patients at a high or very high global CV risk. The gold standard for diagnosis is albumin measured in 24-hour urine collection (normal values of less than 30 mg/day, MAU of 30 to 300 mg/day, macroalbuminuria of more than 300 mg/day) or, more practically, the determination of urinary albumin-to-creatinine ratio in a urine morning sample (30 to 300 mg/g). MAU screening is mandatory in individuals at risk of developing or presenting elevated global CV risk. Evidence has shown that intensive treatment could turn MAU into normoalbuminuria. Intensive treatment with the administration of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, in combination with other anti-hypertensive drugs and drugs covering other aspects of CV risk, such as mineralocorticoid receptor antagonists, new anti-diabetic drugs, and statins, can diminish the risk accompanying albuminuria in hypertensive patients with or without CKD and diabetes.
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Affiliation(s)
- Diego Francisco Márquez
- Unidad de Hipertensión Arterial-Servicio de Clínica Médica, Hospital San Bernardo, Salta, Argentina
| | - Gema Ruiz-Hurtado
- Instituto de Investigación Imas12 and Unidad de Hipertensión, Hospital 12 de Octubre, Madrid, Spain
| | - Julian Segura
- Instituto de Investigación Imas12 and Unidad de Hipertensión, Hospital 12 de Octubre, Madrid, Spain
| | - Luis Ruilope
- Instituto de Investigación Imas12 and Unidad de Hipertensión, Hospital 12 de Octubre, Madrid, Spain.,Departamento de Medicina Preventiva y Salud Pública, Universidad Autónoma, Madrid, Spain.,Escuela de Estudios Postdoctorales and Investigación, Universidad de Europa de Madrid, Madrid, Spain
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