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Wen WL, Lee YJ, Hwu DW, Chang YH. Age- and gender-adjusted estimated glomerular filtration rate definition reveals hyperfiltration as a risk factor for renal function deterioration in type 2 diabetes. Diabetes Obes Metab 2024; 26:1636-1643. [PMID: 38303103 DOI: 10.1111/dom.15465] [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: 10/19/2023] [Revised: 01/02/2024] [Accepted: 01/09/2024] [Indexed: 02/03/2024]
Abstract
AIM To assess the role of hyperfiltration for diabetic kidney disease (DKD) progression. MATERIALS AND METHODS A retrospective observational cohort study enrolled type 2 diabetes (T2D) patients with an initial estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m2 or higher. Patients were categorized into two groups: hyperfiltration (eGFR exceeding the age- and gender-specific 95th percentile values from a prior national cohort study) and normofiltration. Rapid DKD progression was defined as an eGFR decline of more than 5 mL/min/1.73m2/year. We used a linear mixed effect model and Cox regression with time-varying covariate model to compare eGFR changes and identify factors associated with rapid DKD progression. RESULTS Of the enrolled 7563 T2D patients, 7.2% had hyperfiltration. The hyperfiltration group exhibited a higher rate of eGFR decline compared with the normofiltration group (-2.0 ± 0.9 vs. -1.1 ± 0.9 mL/min/1.73m2/year; P < .001). During an average follow-up period of 4.65 ± 3.86 years, 24.7% of patients with hyperfiltration experienced rapid DKD progression, compared with 15.7% of patients with normofiltration (P < .001). Cox regression analyses identified that initial hyperfiltration was a significant determinant of rapid DKD progression, with a hazard ratio of 1.66 (95% confidence interval: 1.41-1.95; P < .001). When combined with albuminuria, the risk of progression was further compounded (hazard ratio 1.76-3.11, all P < .001). CONCLUSIONS In addition to using the current Kidney Disease: Improving Global Outcomes CGA classification system, considering glomerular hyperfiltration status can improve the accuracy of predicting DKD progression.
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Affiliation(s)
- Wei-Lun Wen
- Department of Internal Medicine, Lee's Endocrinology Clinic, Pingtung City, Taiwan
| | - Yau-Jiunn Lee
- Department of Internal Medicine, Lee's Endocrinology Clinic, Pingtung City, Taiwan
| | - Der-Wei Hwu
- Department of Internal Medicine, Lee's Endocrinology Clinic, Pingtung City, Taiwan
| | - Yu-Hung Chang
- Department of Internal Medicine, Lee's Endocrinology Clinic, Pingtung City, Taiwan
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Dai ZC, Chen JX, Zou R, Liang XB, Tang JX, Yao CW. Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease. Front Immunol 2023; 14:1213473. [PMID: 37809091 PMCID: PMC10552262 DOI: 10.3389/fimmu.2023.1213473] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 09/06/2023] [Indexed: 10/10/2023] Open
Abstract
Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.
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Affiliation(s)
| | | | | | | | - Ji-Xin Tang
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Diseases of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Cui-Wei Yao
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Diseases of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
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3
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Fu Z, Su X, Zhou Q, Feng H, Ding R, Ye H. Protective effects and possible mechanisms of catalpol against diabetic nephropathy in animal models: a systematic review and meta-analysis. Front Pharmacol 2023; 14:1192694. [PMID: 37621314 PMCID: PMC10446169 DOI: 10.3389/fphar.2023.1192694] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
Aim of the Study: Rehmannia glutinosa is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years. Catalpol is the main active compound in Rehmannia roots. Current evidence suggests that catalpol exhibits significant anti-diabetic bioactivity, and thus it has attracted increasing research attention for its potential use in treating DN. However, no studies have systematically evaluated these effects, and its mechanism of action remains unclear. This study aimed to evaluate the effects of catalpol on DN, as well as to summarize its possible mechanisms of action, in DN animal models. Materials and Methods: We included all DN-related animal studies with catalpol intervention. These studies were retrieved by searching eight databases from their dates of inception to July 2022. In addition, we evaluated the methodological quality of the included studies using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool. Furthermore, we calculated the weighted standard mean difference (SMD) with 95% confidence interval (CI) using the Review Manager 5.3 software and evaluated publication bias using the Stata (12.0) software. A total of 100 studies were retrieved, of which 12 that included 231 animals were finally included in this review. Results: As compared to the control treatment, treatment with catalpol significantly improved renal function in DN animal models by restoring serum creatinine (Scr) (p = 0.0009) and blood urea nitrogen (BUN) (p < 0.00001) levels, reducing proteinuria (p < 0.00001) and fasting blood glucose (FBG) (p < 0.0001), improving kidney indices (p < 0.0001), and alleviating renal pathological changes in the animal models. In addition, it may elicit its effects by reducing inflammation and oxidative stress, improving podocyte apoptosis, regulating lipid metabolism, delaying renal fibrosis, and enhancing autophagy. Conclusion: The preliminary findings of this preclinical systematic review suggest that catalpol elicits significant protective effects against hyperglycemia-induced kidney injury. However, more high-quality studies need to be carried out in the future to overcome the methodological shortcomings identified in this review.
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Affiliation(s)
- Zhongmei Fu
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaojuan Su
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qi Zhou
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haoyue Feng
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Rui Ding
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hejiang Ye
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Adverse Effects of Angiotensin-Converting Enzyme Inhibitors in Humans: A Systematic Review and Meta-Analysis of 378 Randomized Controlled Trials. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19148373. [PMID: 35886227 PMCID: PMC9324875 DOI: 10.3390/ijerph19148373] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/06/2022] [Accepted: 07/06/2022] [Indexed: 11/29/2022]
Abstract
Background: Although angiotensin-converting enzyme (ACE) inhibitors are among the most-prescribed medications in the world, the extent to which they increase the risk of adverse effects remains uncertain. This study aimed to systematically determine the adverse effects of ACE inhibitors versus placebo across a wide range of therapeutic settings. Methods: Systematic searches were conducted on PubMed, Web of Science, and Cochrane Library databases. Randomized controlled trials (RCTs) comparing an ACE inhibitor to a placebo were retrieved. The relative risk (RR) and its 95% confidence interval (95% CI) were utilized as a summary effect measure. A random-effects model was used to calculate pooled-effect estimates. Results: A total of 378 RCTs fulfilled the eligibility criteria, with 257 RCTs included in the meta-analysis. Compared with a placebo, ACE inhibitors were associated with an significantly increased risk of dry cough (RR = 2.66, 95% CI = 2.20 to 3.20, p < 0.001), hypotension (RR = 1.98, 95% CI = 1.66 to 2.35, p < 0.001), dizziness (RR = 1.46, 95% CI = 1.26 to 1.70, p < 0.001), and hyperkalemia (RR = 1.24, 95% CI = 1.01 to 1.52, p = 0.037). The risk difference was quantified to be 0.037, 0.030, 0.017, and 0.009, respectively. Conclusions: We quantified the relative risk of numerous adverse events associated with the use of ACE inhibitors in a variety of demographics. This information can help healthcare providers be fully informed about any potential adverse consequences and make appropriate suggestions for their patients requiring ACE inhibitor therapy.
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Ravindran S, Munusamy S. Renoprotective mechanisms of sodium-glucose co-transporter 2 (SGLT2) inhibitors against the progression of diabetic kidney disease. J Cell Physiol 2021; 237:1182-1205. [PMID: 34713897 DOI: 10.1002/jcp.30621] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 10/02/2021] [Accepted: 10/08/2021] [Indexed: 12/19/2022]
Abstract
Sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) have emerged as a promising class of antidiabetic drugs with cardioprotective and renoprotective effects in patients with type 2 diabetes (T2D). The sodium-glucose co-transporters 1 and 2 (SGLT 1 and SGLT2) located in the renal proximal tubules are responsible for glucose reabsorption from the glomerular filtrate back into the systemic circulation. Inhibition of SGLT2, which accounts for about 90% of the glucose reabsorption, leads to a significant reduction in blood glucose levels and a concomitant increase in the urinary excretion of glucose (glycosuria). Multiple mechanisms contribute to the nephroprotective effects of SGLT2-Is in T2D patients. These include: (1) Restoration of the tubuloglomerular feedback by increasing sodium delivery at macula densa, leading to afferent arteriolar constriction and reduced glomerular hyperfiltration, (2) Decreased activation of the intra-renal renin-angiotensin-aldosterone system, which also contributes to reducing glomerular hyperfiltration, (3) Increased production of ketone bodies, which serves as an alternate fuel for adenosine triphosphate production in mitochondria, which helps in attenuating inflammation, and (4) Protection against hypoxia, oxidative stress, and fibrosis. This review elaborates on the key mechanisms that underlie the nephroprotective effects and the adverse effects of SGLT2-Is in T2D patients with progressive diabetic kidney disease.
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Affiliation(s)
| | - Shankar Munusamy
- Department of Pharmaceutical and Administrative Sciences, Drake University College of Pharmacy and Health Sciences, Des Moines, Iowa, USA
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Loutradis C, Price A, Ferro CJ, Sarafidis P. Renin-angiotensin system blockade in patients with chronic kidney disease: benefits, problems in everyday clinical use, and open questions for advanced renal dysfunction. J Hum Hypertens 2021; 35:499-509. [PMID: 33654237 DOI: 10.1038/s41371-021-00504-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 01/23/2021] [Accepted: 02/03/2021] [Indexed: 01/13/2023]
Abstract
Management of hypertension and albuminuria are considered among the primary goals of treatment to slow the progression of chronic kidney disease (CKD). Renin-angiotensin system (RAS) blockers, i.e., angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are the main drugs to achieve these goals. Seminal studies have showed that RAS blockers present significant renoprotective effects in CKD patients with very high albuminuria. In post hoc analyses of such trials, these renoprotective effects appeared more robust in patients with more advanced CKD. However, randomized trials specifically addressing whether RAS blockers should be initiated or maintained in patients with advanced CKD are scarce and do not include subjects with normoalbuminuria, thus, many clinicians are unconvinced for the beneficial effects of RAS blockade in these patients. Further, the fear of hyperkalemia or acute renal decline is another factor due to which RAS blockers are usually underprescribed and are easily discontinued in patients with more advanced CKD; i.e., those in Stages 4 and 5. This review summarizes evidence from the literature regarding the use of RAS blockers in patients with advanced CKD.
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Affiliation(s)
- Charalampos Loutradis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Anna Price
- Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Charles J Ferro
- Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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7
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Yang HC, Islam MM, Nguyen PAA, Wang CH, Poly TN, Huang CW, Li YCJ. Development of a Web-Based System for Exploring Cancer Risk With Long-term Use of Drugs: Logistic Regression Approach. JMIR Public Health Surveill 2021; 7:e21401. [PMID: 33587043 PMCID: PMC7920756 DOI: 10.2196/21401] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 09/29/2020] [Accepted: 01/17/2021] [Indexed: 02/06/2023] Open
Abstract
Background Existing epidemiological evidence regarding the association between the long-term use of drugs and cancer risk remains controversial. Objective We aimed to have a comprehensive view of the cancer risk of the long-term use of drugs. Methods A nationwide population-based, nested, case-control study was conducted within the National Health Insurance Research Database sample cohort of 1999 to 2013 in Taiwan. We identified cases in adults aged 20 years and older who were receiving treatment for at least two months before the index date. We randomly selected control patients from the patients without a cancer diagnosis during the 15 years (1999-2013) of the study period. Case and control patients were matched 1:4 based on age, sex, and visit date. Conditional logistic regression was used to estimate the association between drug exposure and cancer risk by adjusting potential confounders such as drugs and comorbidities. Results There were 79,245 cancer cases and 316,980 matched controls included in this study. Of the 45,368 associations, there were 2419, 1302, 662, and 366 associations found statistically significant at a level of P<.05, P<.01, P<.001, and P<.0001, respectively. Benzodiazepine derivatives were associated with an increased risk of brain cancer (adjusted odds ratio [AOR] 1.379, 95% CI 1.138-1.670; P=.001). Statins were associated with a reduced risk of liver cancer (AOR 0.470, 95% CI 0.426-0.517; P<.0001) and gastric cancer (AOR 0.781, 95% CI 0.678-0.900; P<.001). Our web-based system, which collected comprehensive data of associations, contained 2 domains: (1) the drug and cancer association page and (2) the overview page. Conclusions Our web-based system provides an overview of comprehensive quantified data of drug-cancer associations. With all the quantified data visualized, the system is expected to facilitate further research on cancer risk and prevention, potentially serving as a stepping-stone to consulting and exploring associations between the long-term use of drugs and cancer risk.
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Affiliation(s)
- Hsuan-Chia Yang
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan.,Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Md Mohaimenul Islam
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan.,Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Phung Anh Alex Nguyen
- International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan
| | - Ching-Huan Wang
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
| | - Tahmina Nasrin Poly
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan.,Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chih-Wei Huang
- International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan
| | - Yu-Chuan Jack Li
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,International Center for Health Information Technology, Taipei Medical University, Taipei, Taiwan.,Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Department of Dermatology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan
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8
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Fu EL, Clase CM, Evans M, Lindholm B, Rotmans JI, Dekker FW, van Diepen M, Carrero JJ. Comparative Effectiveness of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in Individuals With Advanced CKD: A Nationwide Observational Cohort Study. Am J Kidney Dis 2020; 77:719-729.e1. [PMID: 33246024 DOI: 10.1053/j.ajkd.2020.10.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 10/15/2020] [Indexed: 01/09/2023]
Abstract
RATIONALE & OBJECTIVE It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy. STUDY DESIGN Observational study in the Swedish Renal Registry, 2007 to 2017. SETTINGS & PARTICIPANTS 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates<30mL/min/1.73m2 (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60mL/min/1.73m2) were evaluated. EXPOSURES RAS inhibitor versus CCB therapy initiation. OUTCOME Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke). ANALYTICAL APPROACH HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates. RESULTS Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs. LIMITATIONS Potential confounding by indication. CONCLUSIONS Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.
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Affiliation(s)
- Edouard L Fu
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
| | - Catherine M Clase
- Department of Medicine and Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada
| | - Marie Evans
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Bengt Lindholm
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Joris I Rotmans
- Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - Friedo W Dekker
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Merel van Diepen
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Juan-Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden
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9
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Blankenburg M, Kovesdy CP, Fett AK, Griner RG, Gay A. Disease characteristics and outcomes in patients with chronic kidney disease and type 2 diabetes: a matched cohort study of spironolactone users and non-users. BMC Nephrol 2020; 21:61. [PMID: 32101152 PMCID: PMC7045439 DOI: 10.1186/s12882-020-01719-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 02/11/2020] [Indexed: 01/13/2023] Open
Abstract
Background Limited evidence has indicated that addition of a steroidal mineralocorticoid receptor antagonist (MRA) to the standard of care reduces proteinuria in patients with diabetic kidney disease (DKD); however, there are limited data regarding real-world MRA use in these patients. This study aimed to describe the characteristics of spironolactone users and non-users with DKD, and to explore their clinical outcomes. Methods This was a non-interventional, retrospective cohort study using demographic and clinical data from a US claims database (PharMetrics Plus) and the Experian consumer data asset during 2006–2015. Baseline characteristics (e.g. comorbidities) and post-inclusion clinical outcomes were described in matched cohorts of spironolactone users and non-users (n = 5465 per group). Results Although matching aligned key demographic and clinical characteristics of the cohorts, a significantly greater proportion of spironolactone users than non-users had oedema, proteinuria, and cardiovascular disease at baseline (P < 0.0001). During the post-inclusion period, disease progression and clinical events of interest such as acute kidney injury were more commonly observed in spironolactone users than non-users. Users also had higher healthcare resource utilization and costs than non-users; however, these differences diminished at later stages of disease. Conclusions In this study, spironolactone users had a greater comorbidity burden at baseline than matched non-users, suggesting that the presence of certain comorbidities may be contributing factors in the decision to prescribe spironolactone. High healthcare resource utilization and costs for patients at later stages of disease, irrespective of spironolactone use, highlight the need for new therapies for DKD.
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Affiliation(s)
- Michael Blankenburg
- Market Access, Public Affairs & Sustainability, Pharmaceuticals, Bayer AG, Berlin, Germany.
| | - Csaba P Kovesdy
- Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA
| | | | | | - Alain Gay
- Medical Affairs & Pharmacovigilance, Pharmaceuticals, Bayer AG, Berlin, Germany
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10
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Oh HJ, Kim CT, Ryu DR. Effect of Renin-Angiotensin System Blockade on Mortality in Korean Hypertensive Patients with Proteinuria. Electrolyte Blood Press 2020; 17:25-35. [PMID: 31969921 PMCID: PMC6962440 DOI: 10.5049/ebp.2019.17.2.25] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 10/10/2019] [Accepted: 10/28/2019] [Indexed: 01/13/2023] Open
Abstract
Background Although renin-angiotensin system (RAS) blockade is recommended for hypertensive patients with proteinuria, the effect of RAS blockade on Korean hypertensive patients has not been investigated. Methods Among individuals who underwent a National Health Examination between 2002 and 2003 in Korea, hypertensive patients with proteinuria (defined as a dipstick test result ≥2+) were enrolled in this study. We investigated the outcomes of two groups stratified by RAS blockade prescription (with RAS blockade vs. without RAS blockade). Moreover, Cox proportional hazard regression and Kaplan-Meier analyses were performed to examine the effects of RAS blockade on mortality and end-stage renal disease (ESRD). Results A total of 8,460 patients were enrolled in this study, of whom 6,236 (73.7%) were prescribed with RAS blockade. The mean follow-up period was 129 months. A total of 1,003 (11.9%) patients died, of whom 273 (3.2%) died of cardiovascular (CV) events. The Kaplan-Meier curves for all-cause or CV mortality showed that the survival probability was significantly higher in the RAS blockade group than in the non-RAS blockade group. Multivariate Cox analysis also revealed RAS blockade significantly reduced the all-cause and CV mortality rates by 39.1% and 33.7%, respectively, compared with non-RAS blockade, even after adjusting for age, sex, and comorbid diseases; however, ESRD was not affected. Conclusion In this study, we found that RAS blockade was significantly associated with a reduction in mortality but not in the incidence of ESRD. However, 26.3% of the enrolled patients did not use RAS blockade. Physicians need to consider the usefulness of RAS blockade in hypertensive patients with proteinuria.
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Affiliation(s)
- Hyung Jung Oh
- Ewha Institute of Convergence Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Clara Tammy Kim
- Institute of Life and Death Studies, Hallym University, Chuncheon, Korea
| | - Dong-Ryeol Ryu
- School of Medicine, Ewha Womans University, Seoul, Korea.,Tissue Injury Defense Research Center, Ewha Womans University, Seoul, Korea
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Caravaca-Fontán F, Valladares J, Díaz-Campillejo R, Barroso S, Luna E, Caravaca F. Efecto negativo del bloqueo del sistema renina-angiotensina sobre la progresión de la enfermedad renal crónica avanzada: ¿una cuestión de ajuste de dosis? Nefrologia 2020; 40:38-45. [DOI: 10.1016/j.nefro.2019.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 11/10/2018] [Accepted: 02/24/2019] [Indexed: 10/26/2022] Open
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12
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Tanaka N, Yamamoto Y, Yokoyama Y, Mori T, Hanai K, Babazono T. Temporal trends in the prevalence of albuminuria and reduced eGFR in Japanese patients with type 2 diabetes. Diabetol Int 2019; 10:279-287. [PMID: 31592404 DOI: 10.1007/s13340-019-00392-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 02/22/2019] [Indexed: 01/12/2023]
Abstract
Changes over time have been shown in renal manifestations in individuals with diabetes in the United States; however, whether the trends are shared across ethnicities is unknown. We conducted this single-center serial cross-sectional study to determine temporal changes in albuminuria and reduced kidney function in Japanese patients with type 2 diabetes. This study included adult Japanese patients with type 2 diabetes who first visited our institute between 2004 and 2013. Temporal changes during the 10 years in the frequency of albuminuria ( ≥ 30 mg/g creatinine) and reduced eGFR ( < 60 mL/min/1.73 m2) were analyzed using the univariate and multivariate logistic regression analyses and Granger causality test. 5331 Japanese patients with type 2 diabetes, 1892 women and 3439 men, with the mean age of 56 ± 13 years, were studied. There was no change in the prevalence of albuminuria in the univariate analysis; however, a significantly decreasing trend was observed after adjustment for several covariates. On the other hand, patients with reduced eGFR significantly increased over time, although the statistical significance disappeared after adjustment for the covariates, including levels of serum uric acid and hemoglobin and use of renin-angiotensin inhibitors. The Granger causality test showed that time series for use of RAS inhibitors and BMI had a causative role in time series for reduced eGFR. In conclusion, prevalence of albuminuria decreased and that of reduced eGFR remained stable after adjustment for clinical characteristics in Japanese patients with type 2 diabetes during the last decade.
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Affiliation(s)
- Nobue Tanaka
- Department of Medicine, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
| | - Yui Yamamoto
- Department of Medicine, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
| | - Yoichi Yokoyama
- Department of Medicine, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
| | - Tomomi Mori
- Department of Medicine, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
| | - Ko Hanai
- Department of Medicine, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
| | - Tetsuya Babazono
- Department of Medicine, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
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13
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Methylglyoxal stress, the glyoxalase system, and diabetic chronic kidney disease. Curr Opin Nephrol Hypertens 2019; 28:26-33. [DOI: 10.1097/mnh.0000000000000465] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Garlo KG, Bates DW, Seger DL, Fiskio JM, Charytan DM. Association of Changes in Creatinine and Potassium Levels After Initiation of Renin Angiotensin Aldosterone System Inhibitors With Emergency Department Visits, Hospitalizations, and Mortality in Individuals With Chronic Kidney Disease. JAMA Netw Open 2018; 1:e183874. [PMID: 30646338 PMCID: PMC6324397 DOI: 10.1001/jamanetworkopen.2018.3874] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
IMPORTANCE Renin angiotensin aldosterone system inhibitors (RAASIs) benefit individuals with chronic kidney disease (CKD). Elevations in serum creatinine and potassium levels are common reasons for discontinuation of this therapy, but their incidence and risks are not well characterized in community practice. OBJECTIVE To evaluate associations of increased creatinine levels, hyperkalemia, and therapy continuation with the risk of emergency department (ED) visits, hospitalizations, and mortality within 1 year after RAASI therapy initiation in individuals with CKD. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study included 4661 individuals with nondialysis CKD newly prescribed a RAASI or a diuretic who were treated at 36 outpatient primary care offices affiliated with Brigham & Women's Hospital and Massachusetts General Hospital, Boston, from January 1, 2009, through December 31, 2011. Individuals receiving a new prescription for a diuretic were used to provide context. All participants had a baseline measure of renal function and at least 1 follow-up measurement of creatinine and potassium levels within 90 days of the prescription. Data were analyzed from January 1, 2009, through December 31, 2012. EXPOSURES Changes in creatinine and potassium levels within 90 days after the prescription date and therapy discontinuation. MAIN OUTCOMES AND MEASURES Emergency department visits, hospitalizations, and mortality within 1 year. RESULTS A total of 4661 individuals were included in the analysis (2506 [53.8%] women; mean [SD] age, 71 [14]; 3931 [84.3%] white; and 4198 [90.1%] with CKD stage 3). Of these, 2354 individuals (50.5%) received RAASIs and 2307 (49.5%) received diuretics. Creatinine level increase of at least 30% after RAASI therapy initiation was found in 158 of 2354 individuals (6.7%); hyperkalemia of greater than 5.0 mEq/L, in 251 of 2354 (10.7%). Increases in creatinine level of at least 30% (unadjusted odds ratio [OR], 1.40; 95% CI, 0.89-2.21), hyperkalemia (unadjusted OR, 1.15; 95% CI, 0.64-2.06), and therapy discontinuation (unadjusted OR, 1.01; 95% CI, 0.71-1.46) were not associated with ED visits or hospitalizations, which was consistent with results from competing risk analyses. Initial increases in creatinine level of at least 30% were associated with mortality in the total cohort (adjusted OR [aOR], 2.17; 95% CI, 1.45-3.25). However, the effect was only independent for diuretics (aOR, 2.27; 95% CI, 1.41-3.66) and not for RAASIs (aOR, 1.82; 95% CI, 0.83-3.99). CONCLUSIONS AND RELEVANCE Acute creatinine and potassium level disturbances after initiation of RAASI therapy in individuals with CKD appear to be sustained often often not sustained and not associated with ED visits or hospitalizations, despite therapy continuation. Findings from this study suggest that increases in creatinine level were independently associated with mortality among individuals prescribed diuretics but not RAASIs. Structured laboratory monitoring during RAASI therapy initiation may guide appropriate continuation of therapy in the outpatient setting.
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Affiliation(s)
- Katherine G. Garlo
- Department of Medicine, Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
| | - David W. Bates
- The Center for Patient Safety Research and Practice, Division of General Internal Medicine and Primary Care, Brigham & Women’s Hospital, Boston, Massachusetts
- Clinical and Quality Analysis, Partners HealthCare, Somerville, Massachusetts
| | - Diane L. Seger
- The Center for Patient Safety Research and Practice, Division of General Internal Medicine and Primary Care, Brigham & Women’s Hospital, Boston, Massachusetts
- Clinical and Quality Analysis, Partners HealthCare, Somerville, Massachusetts
| | - Julie M. Fiskio
- The Center for Patient Safety Research and Practice, Division of General Internal Medicine and Primary Care, Brigham & Women’s Hospital, Boston, Massachusetts
- Clinical and Quality Analysis, Partners HealthCare, Somerville, Massachusetts
| | - David M. Charytan
- Department of Medicine, Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
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15
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Magagnotti C, Zerbini G, Fermo I, Carletti RM, Bonfanti R, Vallone F, Andolfo A. Identification of nephropathy predictors in urine from children with a recent diagnosis of type 1 diabetes. J Proteomics 2018; 193:205-216. [PMID: 30366120 DOI: 10.1016/j.jprot.2018.10.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 10/05/2018] [Accepted: 10/22/2018] [Indexed: 02/08/2023]
Abstract
Despite research progresses, the chance to accurately predict the risk for diabetic nephropathy (DN) is still poor. So far, the first evidence of DN is micro-albuminuria, which is detected only 10-20 years after the onset of diabetes. Our goal is to develop new predictive tools of nephropathy starting from urine, which can be easily obtained using noninvasive procedures and it is directly related to kidney. Since it is reasonable to suppose that, in predisposed patients, the mechanisms leading to nephropathy start acting since the diabetes onset, urine from children with recent diagnosis of type 1 diabetes was subjected to proteomic analysis in comparison to age-matched controls. Targeted confirmation was performed on children with a longer history of diabetes using Western Blotting and applying a urinary lipidomic approach. To definitively understand whether the observed alterations could be related to diabetic nephropathy, urine from diabetic adults with or without albuminuria was also examined. For the first time, lipid metabolisms of prostaglandin and ceramide, which are significantly and specifically modified in association with DN, are shown to be already altered in children with a recent diabetes diagnosis. Future studies on larger cohorts are needed to improve the validity and generalizability of these findings. Data are available via ProteomeXchange with identifier PXD011183 Submission details: Project Name: Urinary proteomics by 2DE and LC-MS/MS. Project accession: PXD011183 Project DOI: https://doi.org/10.6019/PXD011183 SIGNIFICANCE: Nephropathy is a very common diabetic complication. Once established, its progression can only be slowed down but full control or remission is achieved in very few cases, thus posing a large burden on worldwide health. The first evidence of diabetic nephropathy (DN) is micro-albuminuria, but only 30% of patients with micro-albuminuria progress to proteinuria, while in some patients it spontaneously reverts to normo-albuminuria. Thus, there is clear need for biomarkers that can accurately predict the risk to develop DN. Herein, by applying proteomic and lipidomic approaches on urine samples, we show that alteration of prostaglandin and ceramide metabolisms specifically occurs in association with DN. Interestingly, we demonstrate that the modification of these metabolic pathways is an early event in diabetic patients, suggesting the identified changed proteins as possible predictive biomarkers of diabetes-induced renal function decline.
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Affiliation(s)
- Cinzia Magagnotti
- ProMiFa, Protein Microsequencing Facility, San Raffaele Scientific Institute, Milan, Italy
| | - Gianpaolo Zerbini
- Complications of Diabetes Unit, Diabetes Research Institute (DRI), San Raffaele Scientific Institute, Milan, Italy
| | - Isabella Fermo
- Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy
| | - Rose Mary Carletti
- Molecular Medicine Program, Department of Experimental Oncology, European Institute of Oncology, Italy; IFOM, The FIRC Institute for Molecular Oncology Foundation, Milan, Italy
| | - Riccardo Bonfanti
- Childhood Diabetes Unit, San Raffaele Scientific Institute, Milan, Italy
| | - Fabiana Vallone
- ProMiFa, Protein Microsequencing Facility, San Raffaele Scientific Institute, Milan, Italy
| | - Annapaola Andolfo
- ProMiFa, Protein Microsequencing Facility, San Raffaele Scientific Institute, Milan, Italy.
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16
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Weir MR, Lakkis JI, Jaar B, Rocco MV, Choi MJ, Kramer HJ, Ku E. Use of Renin-Angiotensin System Blockade in Advanced CKD: An NKF-KDOQI Controversies Report. Am J Kidney Dis 2018; 72:873-884. [PMID: 30201547 DOI: 10.1053/j.ajkd.2018.06.010] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 06/08/2018] [Indexed: 12/21/2022]
Abstract
Multiple clinical trials have demonstrated that renin-angiotensin system (RAS) blockade with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers effectively reduces chronic kidney disease (CKD) progression. However, most clinical trials excluded participants with advanced CKD (ie, estimated glomerular filtration rate [eGFR]<30mL/min/1.73m2). It is acknowledged that initiation of RAS blockade is often associated with an acute reduction in eGFR, which is thought to be functional, but may result in long-term preservation of kidney function through the reductions in glomerular intracapillary pressure conferred by these agents. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) report, we discuss the controversies regarding use of RAS blockade in patients with advanced kidney disease. We review available published data on this topic and provide perspective on the impact of RAS blockade on changes in eGFRs and potassium levels. We conclude that more research is needed to evaluate the therapeutic index of RAS blockade in patients with advanced CKD.
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Affiliation(s)
- Matthew R Weir
- Division of Nephrology, Department of Medicine, University of Maryland, School of Medicine, Baltimore, MD.
| | - Jay I Lakkis
- University of Hawaii John A. Burns School of Medicine, Honolulu, HI
| | - Bernard Jaar
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Michael V Rocco
- Division of Nephrology, Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Michael J Choi
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Holly J Kramer
- Division of Nephrology and Hypertension, Department of Public Health Sciences and Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Elaine Ku
- Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA
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17
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Brooks JM, Chapman CG, Suneja M, Schroeder MC, Fravel MA, Schneider KM, Wilwert J, Li YJ, Chrischilles EA, Brenton DW, Brenton M, Robinson J. Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for Geriatric Ischemic Stroke Patients: Are the Rates Right? J Am Heart Assoc 2018; 7:e009137. [PMID: 29848495 PMCID: PMC6015383 DOI: 10.1161/jaha.118.009137] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 04/12/2018] [Indexed: 01/13/2023]
Abstract
BACKGROUND Our objective is to estimate the effects associated with higher rates of renin-angiotensin system antagonists, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARBs), in secondary prevention for geriatric (aged >65 years) patients with new ischemic strokes by chronic kidney disease (CKD) status. METHODS AND RESULTS The effects of ACEI/ARBs on survival and renal risk were estimated by CKD status using an instrumental variable (IV) estimator. Instruments were based on local area variation in ACEI/ARB use. Data abstracted from charts were used to assess the assumptions underlying the instrumental estimator. ACEI/ARBs were used after stroke by 45.9% and 45.2% of CKD and non-CKD patients, respectively. ACEI/ARB rate differences across local areas grouped by practice styles were nearly identical for CKD and non-CKD patients. Higher ACEI/ARB use rates for non-CKD patients were associated with higher 2-year survival rates, whereas higher ACEI/ARB use rates for patients with CKD were associated with lower 2-year survival rates. While the negative survival estimates for patients with CKD were not statistically different from zero, they were statistically lower than the estimates for non-CKD patients. Confounders abstracted from charts were not associated with the instrumental variable used. CONCLUSIONS Higher ACEI/ARB use rates had different survival implications for older ischemic stroke patients with and without CKD. ACEI/ARBs appear underused in ischemic stroke patients without CKD as higher use rates were associated with higher 2-year survival rates. This conclusion is not generalizable to the ischemic stroke patients with CKD, as higher ACEI/ARBS use rates were associated with lower 2-year survival rates that were statistically lower than the estimates for non-CKD patients.
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Affiliation(s)
- John M Brooks
- Arnold School of Public Health, University of South Carolina, Columbia, SC
| | - Cole G Chapman
- Arnold School of Public Health, University of South Carolina, Columbia, SC
| | - Manish Suneja
- University of Iowa Hospitals and Clinics, Iowa City, IA
| | | | | | | | | | - Yi-Jhen Li
- Arnold School of Public Health, University of South Carolina, Columbia, SC
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Owiredua C, Quarshie ENB, Atorkey P. Living with diabetes: An exploratory study of illness representation and medication adherence in Ghana. COGENT MEDICINE 2018. [DOI: 10.1080/2331205x.2018.1463599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Affiliation(s)
- Christiana Owiredua
- Department of Psychology, University of Ghana, P.O. Box LG 84, Legon, Accra, Ghana
| | | | - Prince Atorkey
- Department of Psychology, University of Ghana, P.O. Box LG 84, Legon, Accra, Ghana
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19
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Vejakama P, Ingsathit A, McKay GJ, Maxwell AP, McEvoy M, Attia J, Thakkinstian A. Treatment effects of renin-angiotensin aldosterone system blockade on kidney failure and mortality in chronic kidney disease patients. BMC Nephrol 2017; 18:342. [PMID: 29187194 PMCID: PMC5706339 DOI: 10.1186/s12882-017-0753-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 11/14/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) is a leading cause of death before and after onset of end-stage renal disease (ESRD). Knowing treatments that can delay disease progression will lead to reduced mortality. We therefore aimed to estimate the effectiveness of renin angiotensin aldosterone system (RAAS) blockade on CKD progression. METHODS We conducted a retrospective CKD cohort at Ubon Ratchathani province, Thailand from 1997 to 2011. ESRD was defined as estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2, dialysis, or kidney transplantation. All-cause mortality was verified until December 31, 2011. A counterfactual-framework was applied to estimate the effectiveness of RAAS blockade on outcomes, i.e., ESRD, death before and after ESRD. RAAS blockade was categorized according to duration of use <0.25 year, 0.25-1 year (RAAS1), and >1 year (RAAS2). An augmented inverse-probability weighting (AIPW) method was used to estimate potential-outcome mean (POM) and average treatment-effect (ATE). Multi-logit and Poisson regressions were used for treatment and outcome models, respectively. Analyses were stratified by ESRD, death before/after ESRD for diabetic and non-diabetic groups. STATA 14.0 was used for statistical analyses. RESULTS Among 15,032 diabetic patients, 2346 (15.6%), 2351 (18.5%), and 1607 (68.5%) developed ESRD, died before ESRD, and died after ESRD, respectively. Only RAAS2 effect was significant on ESRD, death before and after ESRD. The ESRD rates were 12.9%, versus 20.0% for RAAS2 and non-RAAS, respectively, resulted in significant risk differences (RD) of -7.2% (95% CI: -8.8%, -5.5%), and a numbers needed-to-treat (NNT) of 14. Death rates before ESRD for these corresponding groups were 14.4% (12.9%, 15.9%) and 19.6% (18.7%, 20.4%) with a NNT of 19. Death rates after ESRD in RAAS2 was lower than non-RASS group (i.e., 62.8% (55.5%, 68.9%) versus 68.1% (65.9%, 70.4%)) but this was not significant. RAAS2 effects on ESRD and death before ESRD were persistently significant in non-diabetic patients (n = 17,074) but not for death after ESRD with the NNT of about 15 and 16 respectively. CONCLUSIONS Receiving RAAS blockade for 1 year or longer could prevent both CKD progression to ESRD and premature mortality.
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Affiliation(s)
- Phisitt Vejakama
- Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Department of Medicine, Sunpasitthiprasong Hospital, Province, Ubon Ratchathani, Thailand
| | - Atiporn Ingsathit
- Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Gareth J. McKay
- Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland
| | | | - Mark McEvoy
- Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health and Medicine, University of New Castle, NSW, Australia
| | - John Attia
- Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health and Medicine, University of New Castle, NSW, Australia
| | - Ammarin Thakkinstian
- Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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20
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Koye DN, Shaw JE, Reid CM, Atkins RC, Reutens AT, Magliano DJ. Incidence of chronic kidney disease among people with diabetes: a systematic review of observational studies. Diabet Med 2017; 34:887-901. [PMID: 28164387 DOI: 10.1111/dme.13324] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/31/2017] [Indexed: 12/26/2022]
Abstract
AIMS The aim was to systematically review published articles that reported the incidence of chronic kidney disease among people with diabetes. METHODS A systematic literature search was performed using MEDLINE, Embase and CINAHL databases. The titles and abstracts of all publications identified by the search were reviewed and 10 047 studies were retrieved. RESULTS A total of 71 studies from 30 different countries with sample sizes ranging from 505 to 211 132 met the inclusion criteria. The annual incidence of microalbuminuria and albuminuria ranged from 1.3% to 3.8% for Type 1 diabetes. For Type 2 diabetes and studies combining both diabetes types, the range was from 3.8% to 12.7%, with four of six studies reporting annual rates between 7.4% and 8.6%. In studies reporting the incidence of eGFR < 60 ml/min/1.73 m2 using the Modification of Diet on Renal Disease (MDRD) equation, apart from one study which reported an annual incidence of 8.9%, the annual incidence ranged from 1.9% to 4.3%. The annual incidence of end-stage renal disease ranged from 0.04% to 1.8%. CONCLUSIONS The annual incidence of microalbuminuria and albuminuria is ~ 2-3% in Type 1 diabetes, and ~ 8% in Type 2 diabetes or mixed diabetes type. The incidence of developing eGFR < 60 ml/min/1.73 m2 is ~ 2-4% per year. Despite the wide variation in methods and study design, within a particular category of kidney disease, there was only modest variation in incidence rates. These findings may be useful in clinical settings to help understand the risk of developing kidney disease among those with diabetes.
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Affiliation(s)
- D N Koye
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - J E Shaw
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - C M Reid
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
- School of Public Health, Curtin University, Perth, Australia
| | - R C Atkins
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - A T Reutens
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - D J Magliano
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
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21
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Oh YJ, Kim SM, Shin BC, Kim HL, Chung JH, Kim AJ, Ro H, Chang JH, Lee HH, Chung W, Lee C, Jung JY. The Impact of Renin-Angiotensin System Blockade on Renal Outcomes and Mortality in Pre-Dialysis Patients with Advanced Chronic Kidney Disease. PLoS One 2017; 12:e0170874. [PMID: 28122064 PMCID: PMC5266335 DOI: 10.1371/journal.pone.0170874] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 01/11/2017] [Indexed: 01/13/2023] Open
Abstract
Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071–1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123–1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016–1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996–1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.
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Affiliation(s)
- Yun Jung Oh
- Division of Nephrology, Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
| | - Sun Moon Kim
- Division of Nephrology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea
| | - Byung Chul Shin
- Division of Nephrology, Department of Internal Medicine, Chosun University Hospital, Gwangju, Korea
| | - Hyun Lee Kim
- Division of Nephrology, Department of Internal Medicine, Chosun University Hospital, Gwangju, Korea
| | - Jong Hoon Chung
- Division of Nephrology, Department of Internal Medicine, Chosun University Hospital, Gwangju, Korea
| | - Ae Jin Kim
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
- Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea
| | - Han Ro
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
- Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea
| | - Jae Hyun Chang
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
- Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea
| | - Hyun Hee Lee
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
- Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea
| | - Wookyung Chung
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
- Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea
| | - Chungsik Lee
- Division of Nephrology, Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
| | - Ji Yong Jung
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
- Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea
- * E-mail:
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22
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Chang YH, Lei CC, Lin KC, Chang DM, Hsieh CH, Lee YJ. Serum uric acid level as an indicator for CKD regression and progression in patients with type 2 diabetes mellitus-a 4.6-year cohort study. Diabetes Metab Res Rev 2016; 32:557-64. [PMID: 26590369 DOI: 10.1002/dmrr.2768] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Revised: 09/27/2015] [Accepted: 10/28/2015] [Indexed: 11/07/2022]
Abstract
BACKGROUND To investigate the association of serum uric acid level with renal function change in patients with type 2 diabetes mellitus (T2DM). METHODS T2DM patients who had been followed-up for at least 3 years were included. Participants were categorized into stable, progression, or regression groups according to their change in chronic kidney disease (CKD) stage. During the follow-up period, all numeric values of metabolic factors, including the uric acid level and the medication possession rate, were calculated in order to investigate their associations with CKD development. Multivariate Cox regression analyses were used to identify independent factors associated with change in CKD. RESULTS A total of 2367 T2DM patients were enrolled in this study and followed-up for a mean of 4.6 years. The numbers of patients in the stable, progression and regression groups were 1133 (47.9%), 487 (20.6%), and 747 (31.5%), respectively. The progression group had the highest serum uric acid level (6.9 ± 1.8 mg/dL), and the regression group had the lowest uric acid level (5.4 ± 1.5 mg/dL). In addition, we found that the serum uric acid level was an independent factor associated with CKD progression when the value exceeded 6.3 mg/dL. A lower uric acid level could be beneficial for CKD improvement in T2DM patients with stage 3-5 CKD. CONCLUSIONS Our data indicated that the serum uric acid level is associated with CKD regression and progression and suggested that a high normal serum uric acid level should be closely monitored in patients with T2DM. Copyright © 2015 John Wiley & Sons, Ltd.
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Affiliation(s)
| | | | | | | | - Chang-Hsun Hsieh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
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23
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Adam WR, Wright JR. Use of renin angiotensin system inhibitors in patients with chronic kidney disease. Intern Med J 2016; 46:626-30. [PMID: 27170242 DOI: 10.1111/imj.13060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Accepted: 01/19/2016] [Indexed: 01/13/2023]
Abstract
Current guidelines recommend renin angiotensin system inhibitors (RASI) as key components of treatment of hypertension in patients with chronic kidney disease (CKD), because of their effect on reducing the future rate of loss of glomerular filtration rate (GFR). A common risk of RASI in CKD is a haemodynamically mediated, and reversible, fall in GFR of varying severity and duration, any time after commencement of the Inhibitors. A benefit of the acute reduction in filtration rate with RASI may be a reduction in the future rate of loss in GFR: the greatest benefit likely to be in those patients with a greater rate of loss of GFR prior to, and a lesser acute loss of GFR after, introduction of RASI; and in those patients with significant proteinuria. An acute loss of GFR of >25% following the introduction of RASI is an indication to cease the RASI. An acute loss of GFR < 25% requires consideration of the likely risks of the lower GFR and benefits of any future reduced rate of loss of GFR. A fall in GFR in patients while on RASI is usually associated with a remediable cause. When the cause for the fall in GFR is not revealed, and the fall is less than 25%, hopeful expectancy is recommended. Hyperkalaemia in patients with CKD on RASI is more common with more severe disease, potassium retaining diuretics and hypoaldosteronism. Treatment should be modified to maintain a plasma potassium <6 mmol/L.
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Affiliation(s)
- W R Adam
- Department of Rural Health, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia
| | - J R Wright
- Department of Rural Health, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia
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Barzilay JI, Whelton PK, Davis BR. Does renin angiotensin system blockade deserve preferred status over other anti-hypertensive medications for the treatment of people with diabetes? ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:202. [PMID: 27294098 PMCID: PMC4885898 DOI: 10.21037/atm.2016.05.24] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 05/09/2016] [Indexed: 12/20/2022]
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Solbu MD, Jardine AG. 'To block or not to block'; whether to continue renin-angiotensin-aldosterone system blockade in advanced chronic kidney disease. Nephrol Dial Transplant 2015; 31:171-3. [PMID: 26445812 DOI: 10.1093/ndt/gfv351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 09/04/2015] [Indexed: 11/12/2022] Open
Affiliation(s)
- Marit D Solbu
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK University Hospital of North Norway, Tromsø, Norway
| | - Alan G Jardine
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
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Robles NR, Villa J, Gallego RH. Non-Proteinuric Diabetic Nephropathy. J Clin Med 2015; 4:1761-1773. [PMID: 26371050 PMCID: PMC4600158 DOI: 10.3390/jcm4091761] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 08/11/2015] [Accepted: 08/26/2015] [Indexed: 12/13/2022] Open
Abstract
Diabetic nephropathy patients traditionally show significant macroalbuminuria prior to the development of renal impairment. However, this clinical paradigm has recently been questioned. Epidemiological surveys confirm that chronic kidney disease (CKD) diagnosed by a low glomerular filtration rate (GFR) is more common in diabetic patients than in the non-diabetic population but a low number of patients had levels of proteinuria above that which traditionally defines overt diabetic nephropathy (>500 mg/g). The large number of patients with low levels of proteinuria suggests that the traditional clinical paradigm of overt diabetic nephropathy is changing since it does not seem to be the underlying renal lesion in most of diabetic subjects with CKD.
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Affiliation(s)
- Nicolas Roberto Robles
- Cátedra de Riesgo Vascular, Facultad de Medicina, Universidad de Salamanca, Salamanca 37007, Spain.
| | - Juan Villa
- Servicio de Nefrologia, Hospital Infanta Cristina, Badajoz 06070, Spain.
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Suzuki H, Kikuta T, Inoue T, Hamada U. Time to re-evaluate effects of renin-angiotensin system inhibitors on renal and cardiovascular outcomes in diabetic nephropathy. World J Nephrol 2015; 4:118-26. [PMID: 25664254 PMCID: PMC4317622 DOI: 10.5527/wjn.v4.i1.118] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 11/13/2014] [Accepted: 12/03/2014] [Indexed: 02/06/2023] Open
Abstract
The use of renin-angiotensin system (RAS) inhibitors, such angiotensin converting enzyme inhibitors/angiotensin-II receptor blockers, to slow progression of chronic kidney disease (CKD) in a large group dominated by elderly people in the real world is not supported by available evidence. Large-scale clinical trials had many faults, among them a lack of focus on the elderly. However, it would be difficult to conduct clinical trials of a similar scale in elderly CKD patients. Besides, progression of kidney disease is often slow in elderly persons, and the vast majority of older adults with CKD will die before reaching end stage renal disease. Moreover, since it is not clear that progression of kidney disease, and even of proteinuric diabetic nephropathy, is not inhibited through the use of RAS inhibitors, the most patient-centric goal of therapy for many elderly individuals should be individualized.
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Andrésdóttir G, Jensen ML, Carstensen B, Parving HH, Hovind P, Hansen TW, Rossing P. Improved prognosis of diabetic nephropathy in type 1 diabetes. Kidney Int 2015; 87:417-26. [DOI: 10.1038/ki.2014.206] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Revised: 04/07/2014] [Accepted: 04/17/2014] [Indexed: 02/06/2023]
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Jo SH, Lee JM, Park J, Kim HS. The impact of renin-angiotensin-aldosterone system blockade on contrast-induced nephropathy: a meta-analysis of 12 studies with 4,493 patients. Cardiology 2014; 130:4-14. [PMID: 25428235 DOI: 10.1159/000366473] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 08/06/2014] [Indexed: 11/19/2022]
Abstract
OBJECTIVES This meta-analysis investigated the impact of renin-angiotensin-aldosterone system (RAAS) blockade on the occurrence of contrast-induced nephropathy (CIN). METHODS Twelve studies comparing the use of RAAS blockade in a total of 4,493 patients undergoing a contrast-using procedure were included. The primary endpoint was the overall postprocedural incidence of CIN. RESULTS In the overall pooled analysis, there was no significant difference between the two groups, RAAS blockade 'used' versus 'not-used', in the incidence of postprocedural CIN in the random-effects model (OR 1.27, 95% CI 1.77-2.11, p = 0.351, I(2) = 61.9%). In the stratified analysis, however, for chronic RAAS blockade users, the continuation of the drug was significantly associated with a higher incidence of CIN compared with discontinuation (OR 2.06, 95% CI 1.62-2.61, p < 0.001, I2 = 0.0%). A hazard of continuation was marked in a subgroup of older patients or in patients with chronic kidney disease. For drug-naïve patients, however, administration of RAAS blockade before contrast procedures did not reduce the development of CIN significantly (OR 0.52, 95% CI 0.23-1.16, p = 0.108, I2 = 34.2%). CONCLUSION Discontinuation of RAAS blockade in chronic users is associated with a significantly lower incidence of CIN, whereas administration of RAAS blockade as a preventive measure for naïve patients did not show a significant effect on the incidence of CIN.
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Affiliation(s)
- Sang-Ho Jo
- Division of Cardiology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang-si, South Korea
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Abdelhafiz AH, Nahas ME, de Oliveira JMF. Management of diabetic nephropathy in older patients: a need for flexible guidelines. Postgrad Med 2014; 126:171-7. [PMID: 25141254 DOI: 10.3810/pgm.2014.07.2794] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
As the population ages and diabetes mellitus increases in prevalence, the incidence of diabetic nephropathy (DN) is becoming a disease of older people (aged ≥ 75 years). As the epidemiology of diabetes mellitus and DN shifts toward this patient population, the pathogenesis of DN in old age is changing: the pathologic findings suggest ischemia and hypertension, and the classic Kimmelstiel-Wilson lesions may be absent. The demographic shift in the epidemiology and the associated changes in pathology because of aging and atherosclerosis will have a significant impact on various aspects related to the disease in old age. This article reviews the authors' current understanding of DN and its implications on clinical management relevant to current guidelines.
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Affiliation(s)
- Ahmed H Abdelhafiz
- Department of Elderly Medicine, Rotherham General Hospital, Rotherham, UK.
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Andrésdóttir G, Jensen ML, Carstensen B, Parving HH, Rossing K, Hansen TW, Rossing P. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors. Diabetes Care 2014; 37:1660-7. [PMID: 24623028 DOI: 10.2337/dc13-2036] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors have become standard of care. RESEARCH DESIGN AND METHODS All patients with type 2 diabetes and DN (n = 543) at the Steno Diabetes Center were followed during 2000-2010. GFR was measured yearly with 51Cr-EDTA plasma clearance. Annual decline in GFR was determined in patients with at least three measurements over a minimum of 3 years (∆GFR cohort, n = 286). Results were compared with historical data, obtained using identical criteria at our hospital, before implementation of current treatment guidelines. RESULTS Baseline mean (SD) GFR was 74 (32) mL/min/1.73 m2. More than 93% received RAS inhibition. During median 7.8 (interquartile range 5.7-9.8) years, mean (SE) annual GFR decline was 4.4 (0.24) compared with previously 5.2 (0.27) mL/min/1.73 m2/year (P = 0.04). Doubling of plasma creatinine or end-stage renal disease (ESRD) developed in 19%, and 37% died during 5.7 (3.3-8.8) years. Mortality from onset of DN in the ∆GFR cohort was compared with that of our prior ∆GFR cohort from 1983 to 2003 (n = 227). Crude mortality risk was reduced by 42% and after age adjustment by 50% (P < 0.001 for both). In a multistate model accounting for competing risks of ESRD and death, prior cardiovascular disease and lower GFR were predictors of mortality, whereas albuminuria, HbA1c, and low GFR predicted ESRD. CONCLUSIONS Overall prognosis has improved considerably with current multifactorial treatment of DN in type 2 diabetes, including long-term RAS inhibition.
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Affiliation(s)
| | | | | | - Hans-Henrik Parving
- Department of Medical Endocrinology, Rigshospitalet, Copenhagen, DenmarkFaculty of Health Science, University of Copenhagen, Copenhagen, DenmarkHEALTH, University of Aarhus, Aarhus, Denmark
| | - Kasper Rossing
- Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
| | | | - Peter Rossing
- Steno Diabetes Center, Gentofte, DenmarkFaculty of Health Science, University of Copenhagen, Copenhagen, DenmarkHEALTH, University of Aarhus, Aarhus, Denmark
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Woo KT, Wong KS, Lee EJC, Chan CM. Addressing the Plight of Patients with Kidney Failure. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2013. [DOI: 10.47102/annals-acadmedsg.v42n12p629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Resistive index as a predictor of acute kidney injury caused by an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker in chronic kidney disease patients. Kidney Res Clin Pract 2013; 32:158-63. [PMID: 26877935 PMCID: PMC4714154 DOI: 10.1016/j.krcp.2013.09.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 08/23/2013] [Accepted: 09/18/2013] [Indexed: 01/01/2023] Open
Abstract
Background Angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) may induce acute kidney injury (AKI). The aim of this study was to evaluate the role of the resistive index (RI), which reflects renal artery resistance on renal duplex ultrasonography, as a predictor of AKI in chronic kidney disease (CKD) patients who are prescribed an ACE inhibitor or ARB. Methods We screened 105 CKD patients evaluated with renal duplex ultrasonography from 2008 to 2012. We excluded patients not treated with ACE inhibitor or ARB and diagnosed with renal artery stenosis. Finally, we retrospectively analyzed the medical records of 54 patients. AKI was defined as increased serum creatinine by >30% compared with baseline after starting ACE inhibitor or ARB treatment. Results The mean age of the patients was 60.5±13.0 years, serum creatinine level was 1.85±0.85 mg/dL and 22.2% of the patients had AKI after the use of an ACE inhibitor or ARB. The RI (P=0.006) and the percentages of patients with diabetes (P=0.008) and using diuretics (P=0.046) were higher in the AKI group. The area under the receiver operating characteristics curve for the prediction of AKI was 0.736 (95% confidence interval=0.587–0.885, P=0.013), and RI≥0.80 predicted AKI with 83.3% sensitivity and 61.9% specificity. In the multivariate analysis, RI≥0.80 was an independent prognostic factor [Exp (B)=8.03, 95% confidence interval=1.14–56.74, P=0.037] for AKI. Conclusion RI≥0.80 on the renal duplex ultrasonography may be a helpful predictor for AKI in CKD patients who are prescribed an ACE inhibitor or ARB.
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Moranne O, Bakris G, Fafin C, Favre G, Pradier C, Esnault VLM. Determinants and changes associated with aldosterone breakthrough after angiotensin II receptor blockade in patients with type 2 diabetes with overt nephropathy. Clin J Am Soc Nephrol 2013; 8:1694-701. [PMID: 23929924 DOI: 10.2215/cjn.06960712] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND OBJECTIVES Inhibition of the renin-angiotensin-aldosterone system decreases proteinuria and slows estimated GFR decline in patients with type 2 diabetes mellitus with overt nephropathy. Serum aldosterone levels may increase during renin-angiotensin-aldosterone system blockade. The determinants and consequences of this aldosterone breakthrough remain unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study examined the incidence, determinants, and changes associated with aldosterone breakthrough in a posthoc analysis of a randomized study that compared the effect of two angiotensin II receptor blockers in patients with type 2 diabetes mellitus with overt nephropathy. RESULTS Of 567 of 860 participants included in this posthoc analysis, 28% of participants developed aldosterone breakthrough, which was defined by an increase greater than 10% over baseline values of serum aldosterone levels after 1 year of angiotensin II receptor blocker treatment. Factors independently associated with aldosterone breakthrough at 1 year were lower serum aldosterone and potassium levels at baseline, higher decreases in sodium intake, systolic BP, and estimated GFR from baseline to 1 year, and use of losartan versus telmisartan. Aldosterone breakthrough at 6 months was not sustained at 1 year in 69% of cases, and it did not predict estimated GFR decrease and proteinuria increase between 6 months and 1 year. CONCLUSIONS Aldosterone breakthrough is a frequent event 1 year after initiating renin-angiotensin-aldosterone system blockade, particularly in participants exposed to intensive lowering of BP with sodium depletion and short-acting angiotensin II receptor blockers. Short-term serum aldosterone level increases at 6 months are not associated with negative kidney outcomes between 6 months and 1 year.
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Affiliation(s)
- Olivier Moranne
- Nephrology and, †Epidemiology Departments, Nice University Hospital, Nice, France;, ‡ASH Comprehensive Hypertension Center, University of Chicago, Chicago, Illinois, §Institut National de la Santé et de la Recherche Médicale U1081, Nice Sophia-Antipolis University, Nice, France
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Molecular Docking and Quantum Mechanical Studies on Pelargonidin-3-Glucoside as Renoprotective ACE Inhibitor. ACTA ACUST UNITED AC 2013. [DOI: 10.1155/2013/428378] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Background and Aim. Despite tangible progress in recent years, substantial therapeutic challenges remain unexplored in nephropathy, particularly in diabetic patient. Addressing these challenges requires identification of novel drugs and development of noninvasive and cost-effective methods to select the most appropriate therapeutic option for the disease. Angiopathic nephropathy is one of the complications of diabetes mellitus and is becoming the single most important reason for end-stage renal disease in the western world. This study has investigated the inhibitory effect of a library naturally occurring nonprotein compounds that inhibit angiotensin converting enzyme (ACE). Materials and Methods. Docking studies of ACE protein with natural compounds and synthetic commercial drug perindopril were done using AutoDock, FlexX, and Hex. Toxicity predictions were carried out using OpenTox. Quantum mechanical properties were studied using GAMESS. Results. Pelargonidin-3-glucoside could be used as a potent renoprotective drug candidate, which inhibits ACEII. It has low toxicity and its quantum mechanical properties are comparable to those of commercial drugs.
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Fogari R, Mugellini A, Zoppi A, Preti P, Maffioli P, Perrone T, Derosa G. Time course of antiproteinuric effect of aliskiren in arterial hypertension associated with type 2 diabetes and microalbuminuria. Expert Opin Pharmacother 2013; 14:371-84. [DOI: 10.1517/14656566.2013.772981] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Affiliation(s)
- Roberto Fogari
- University of Pavia, Clinica Medica II, Centro Ipertensione e Fisiopatologia Cardiovascolare, Department of Internal Medicine and Therapeutics,
Piazzale Golgi 19, 27100 Pavia, Italy ;
| | - Amedeo Mugellini
- University of Pavia, Clinica Medica II, Centro Ipertensione e Fisiopatologia Cardiovascolare, Department of Internal Medicine and Therapeutics,
Piazzale Golgi 19, 27100 Pavia, Italy ;
| | - Annalisa Zoppi
- University of Pavia, Clinica Medica II, Centro Ipertensione e Fisiopatologia Cardiovascolare, Department of Internal Medicine and Therapeutics,
Piazzale Golgi 19, 27100 Pavia, Italy ;
| | - Paola Preti
- University of Pavia, Clinica Medica II, Centro Ipertensione e Fisiopatologia Cardiovascolare, Department of Internal Medicine and Therapeutics,
Piazzale Golgi 19, 27100 Pavia, Italy ;
| | - Pamela Maffioli
- University of Pavia, Clinica Medica II, Centro Ipertensione e Fisiopatologia Cardiovascolare, Department of Internal Medicine and Therapeutics,
Piazzale Golgi 19, 27100 Pavia, Italy ;
| | - Tiziano Perrone
- University of Pavia, Clinica Medica II, Centro Ipertensione e Fisiopatologia Cardiovascolare, Department of Internal Medicine and Therapeutics,
Piazzale Golgi 19, 27100 Pavia, Italy ;
| | - Giuseppe Derosa
- University of Pavia, Clinica Medica II, Centro Ipertensione e Fisiopatologia Cardiovascolare, Department of Internal Medicine and Therapeutics,
Piazzale Golgi 19, 27100 Pavia, Italy ;
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Chapter 8: Future directions and controversies. Kidney Int Suppl (2011) 2012; 2:382-387. [PMID: 25018966 PMCID: PMC4089610 DOI: 10.1038/kisup.2012.58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
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Woo KT, Choong HL, Wong KS, Tan HB, Chan CM. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int 2012; 81:1044-1045. [PMID: 22543907 DOI: 10.1038/ki.2012.39] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Keng-Thye Woo
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore.
| | - Hui L Choong
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
| | - Kok-Seng Wong
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
| | - Hwee Boon Tan
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
| | - Choong-Meng Chan
- Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore
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Abstract
The randomized controlled trial is the fundamental study design to evaluate the effectiveness of medications and receive regulatory approval. Observational studies, on the other hand, are essential to address post-marketing drug safety issues but have also been used to uncover new indications or new benefits for already marketed drugs. Hormone replacement therapy (HRT) for instance, effective for menopausal symptoms, was reported in several observational studies during the 1980s and 1990s to also significantly reduce the incidence of coronary heart disease. This claim was refuted in 2002 by the large-scale Women's Health Initiative randomized trial. An example of a new indication for an old drug is that of metformin, an anti-diabetic medication, which is being hailed as a potential anti-cancer agent, primarily on the basis of several recent observational studies that reported impressive reductions in cancer incidence and mortality with its use. These observational studies have now sparked the conduct of large-scale randomized controlled trials currently ongoing in cancer. We show in this paper that the spectacular effects on new indications or new outcomes reported in many observational studies in chronic obstructive pulmonary disease (COPD), HRT, and cancer are the result of time-related biases, such as immortal time bias, that tend to seriously exaggerate the benefits of a drug and that eventually disappear with the proper statistical analysis. In all, while observational studies are central to assess the effects of drugs, their proper design and analysis are essential to avoid bias. The scientific evidence on the potential beneficial effects in new indications of existing drugs will need to be more carefully assessed before embarking on long and expensive unsubstantiated trials.
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Reboldi G, Gentile G, Manfreda VM, Angeli F, Verdecchia P. Tight blood pressure control in diabetes: evidence-based review of treatment targets in patients with diabetes. Curr Cardiol Rep 2012; 14:89-96. [PMID: 22139528 DOI: 10.1007/s11886-011-0236-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Blood pressure (BP) targets in diabetic patients stills represent the object of a major debate, fueled by the recent publication of post hoc observational analyses of the INVEST and the ONTARGET trials, suggesting an increased risk of cardiovascular events with tighter control, the J-curve effect, and by the results of the ACCORD trial, showing no improvements in the composite primary outcome of nonfatal myocardial infarction, stroke, or cardiovascular death in the intensive BP-lowering arm (<120/80 mmHg). In the present review, we focus on existing evidence about different BP targets in diabetic subjects and we present the results of our recent meta-analysis, showing that tight BP control may significantly reduce the risk of stroke in these patients without increasing the risk of myocardial infarction. Therapeutic inertia (leaving diabetic patients with BP values of 140/90 mmHg or higher) should be avoided at all costs, as this would lead to an unacceptable toll in terms of human lives, suffering, and socioeconomic costs.
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Affiliation(s)
- Gianpaolo Reboldi
- Department of Internal Medicine, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy.
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Gonçalves AR, Khwaja A, Ahmed AK, El Kossi M, El Nahas M. Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response. Nephron Clin Pract 2012; 119:c348-54. [PMID: 22135795 DOI: 10.1159/000330289] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/AIMS Renin-angiotensin system (RAS) inhibitors are considered first-line agents for hypertensive patients with progressive chronic kidney disease (CKD). In a previous study, we showed that stopping RAS inhibitors increased estimated glomerular filtration rate (eGFR) in a significant number of advanced CKD patients. The present study tries to address who would benefit and whether this benefit is predictable. METHODS Forty-three CKD stage 4 patients had RAS inhibitors stopped and were followed for at least 24 months. Compared outcome groups were 'alive', 'renal replacement therapy (RRT)' or 'died'. Improvement in eGFR was used in a receiver-operating characteristic curve and finds the best predictor for surviving without RRT. RESULTS Patients who survived without RRT were all hypertensive and had a higher eGFR increment after stopping the drugs. Those with eGFR improvement ≥5 ml/min/1.73 m(2) were the most likely to survive long term without RRT (log-rank test, p = 0.03). They had a significant increment in blood pressure that correlated with eGFR improvement (r = 0.403, p = 0.013). CONCLUSION A significant increase in eGFR after stopping RAS inhibitors suggests that long-term survival without RRT is more likely. Our findings question the universal preemptive indication of RAS inhibitors in advanced CKD and suggest that they can be safely stopped, at least in some patients.
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Altemtam N, Russell J, El Nahas M. A study of the natural history of diabetic kidney disease (DKD). Nephrol Dial Transplant 2011; 27:1847-54. [PMID: 22058177 DOI: 10.1093/ndt/gfr561] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In view of the alarming increase in the number of people with diabetes mellitus (DM), a rising number of patients with diabetic kidney disease (DKD), end-stage renal disease (ESRD) and cardiovascular disease (CVD) is forecasted. It is therefore imperative to re-visit the natural history of DKD and to identify potential risk factors, which may enhance the progression of the disease and its complications. METHODS The medical records of 270 Type 2 diabetic chronic kidney disease patients followed up at the Sheffield Kidney Institute between 2000 and 2008 were reviewed. Various socio-demographic, clinical and biochemical parameters (baseline and follow-up parameters) were retrospectively collected from the patients' database. Progression of DKD was evaluated by evaluation of the rate of decline of estimated glomerular filtration rate (eGFR) as calculated from the simplified Modification of Diet in Renal Disease formula [progressors: loss of glomerular filtration rate (GFR) >2 mL/min/1.73m(2)/year] as well as by the progression pattern based on the slope of GFR changes. Variables associated with progression in univariate analysis were examined by multivariate analysis to determine the factors independently associated with DKD progression. RESULTS The majority of the study populations were males (66.7%) and Caucasians (88%). Ninety-four patients (34.8%) had progressive, whereas 176 (65.2%) had non-progressive DKD. The rate of eGFR decline in progressors was -3.57 ± 1.45 mL/min/1.73m(2)/year compared to -1.31 ± 0.23 mL/min/1.73m(2)/year in non-progressors. The following parameters discriminated progressors from non-progressors by univariate analysis: baseline-blood pressure (BP) parameters, eGFR and proteinuria as well as serum uric acid. We also observed that area under the curve for follow-up systolic blood pressure (SBP), glycosylated haemoglobin (HbA1c) and proteinuria were significantly higher among the progressors (P = 0.043, P = 0.02 and P = 0.001, respectively). Independent determinants of DKD progression in this study in an adjusted logistic regression model were baseline HbA1c [odds ratio (OR), 2.27; 95% confidence interval (CI), 1.14-4.54], baseline SBP (OR, 1.23; 95% CI, 1.06-1.41), baseline proteinuria (OR, 3.24; 95% CI, 2.1-5.38), baseline serum uric acid (OR, 1.16; 95% CI, 1.09-1.39) and vascular co-morbidities (OR, 1.61; 95% CI, 1.02-2.54). Percentage changes in the key parameters (BP, HbA1c and proteinuria) during the first year of the study did not affect the rate of eGFR decline. CONCLUSIONS Baseline HbA1c, SBP, proteinuria and serum uric acid together with the presence of vascular co-morbidities are strongly and independently associated with faster DKD progression. A further prospective observational study is currently undertaken to evaluate these findings and to determine the predictive value of other biochemical peptides and cellular markers on DKD outcome.
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Affiliation(s)
- Nagi Altemtam
- Academic Nephrology Unit, Sheffield Kidney Institute, University of Sheffield, Sheffield, UK.
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Gonçalves AR, El Nahas AM. High serum potassium levels after using losartan can reflect more severe renal disease. Diabetologia 2011; 54:2963-4; author reply 2965-7. [PMID: 21688085 DOI: 10.1007/s00125-011-2220-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Accepted: 05/25/2011] [Indexed: 12/22/2022]
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Hamming I, Goor HV, Navis GJ. Rat Ace allele variation determines susceptibility to AngII-induced renal damage. J Renin Angiotensin Aldosterone Syst 2011; 70:1377-8; author reply 1378. [PMID: 16988743 DOI: 10.1038/sj.ki.5001684] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Ace b/l polymorphism in rats is associated with differential tissue angiotensin-converting enzyme (ACE) expression and activity, and susceptibility to renal damage. Same polymorphism was recently found in outbred Wistar rat strain with b allele accounting for higher renal ACE, and provided a model for studying renin-angiotensin-aldosterone system (RAAS) response behind the innate high or low ACE conditions. METHODS We investigated the reaction of these alleles on chronic angiotensin II (AngII) infusion. Wistar rats were selected to breed male homozygotes for the b (WU-B) or l allele (WU-L) (n = 12). For each allele, one group (n = 6) received AngII infusion via an osmotic minipump (435 ng/kg/min) for 3 weeks. The other group (n = 6) served as a control. RESULTS WU-B had higher ACE activity at baseline then WU-L. Interestingly, baseline renal ACE2 expression and activity were higher in WU-L. AngII infusion induced the same increase in blood pressure in both genotypes, no proteinuria, but caused tubulo-interstitial renal damage with increased α-SMA and monocyte/macrophage influx only in WU-B (p < 0.05). Low ACE WU-L rats did not develop renal damage. CONCLUSION AngII infusion causes proteinuria-independent renal damage only in rats with genetically predetermined high ACE while rats with low ACE seemed to be protected against the detrimental effect of AngII. Differences in renal ACE2, mirroring those in ACE, might be involved.
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Moriyama T, Tsuruta Y, Kojima C, Itabashi M, Sugiura H, Takei T, Ogawa T, Uchida K, Tsuchiya K, Nitta K. Beneficial effect of aliskiren combined with olmesartan in reducing urinary protein excretion in patients with chronic kidney disease. Int Urol Nephrol 2011; 44:841-5. [PMID: 21626132 DOI: 10.1007/s11255-011-9991-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2011] [Accepted: 05/03/2011] [Indexed: 01/13/2023]
Abstract
BACKGROUND Blockade of the renin-angiotensin-aldosterone system is a therapeutic mainstay in patients with chronic kidney disease (CKD). However, the renoprotective effect of the novel direct renin inhibitor aliskiren is unknown. MATERIALS AND METHODS We performed a prospective study in 10 CKD patients. All 10 patients with persistent proteinuria (urinary protein-to-creatinin ratio 0.3-3.5 g/g), despite good blood pressure control (<130/80 mmHg) with olmesartan, were started on 150 mg/day aliskiren. Clinical parameters were examined before and after 4, 8, 12, and 16 weeks of treatment. RESULTS Urinary protein-to-creatinine ratio significantly decreased by about 40% at 16 weeks from baseline (P = 0.0002), although estimated glomerular filtration rate and blood pressure did not change throughout the study period. Plasma renin activity also decreased significantly from baseline (P = 0.019), although plasma aldosterone concentration did not change. CONCLUSIONS Aliskiren combined with olmesartan reduces proteinuria in CKD patients.
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Affiliation(s)
- Takahito Moriyama
- Department of Medicine, Kidney Center, Tokyo Women's Medical University, Kawada-cho 8-1, Shinjyuku-ku, Tokyo 162-8666, Japan.
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Reboldi G, Gentile G, Angeli F, Verdecchia P. Optimal Therapy in Hypertensive Subjects with Diabetes Mellitus. Curr Atheroscler Rep 2011; 13:176-85. [DOI: 10.1007/s11883-011-0160-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Affiliation(s)
- M A C Onuigbo
- College of Medicine, Mayo Clinic, Rochester, MN, USA.
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Turgut F, Bolton WK. Potential new therapeutic agents for diabetic kidney disease. Am J Kidney Dis 2010; 55:928-40. [PMID: 20138415 DOI: 10.1053/j.ajkd.2009.11.021] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2009] [Accepted: 11/12/2009] [Indexed: 01/05/2023]
Abstract
Diabetic nephropathy is the leading cause of end-stage renal disease, and both the incidence and prevalence of diabetic nephropathy continue to increase. Currently, various treatment regimens and combinations of therapies provide only partial renoprotection. It is obvious that new approaches are desperately needed to retard the progression of diabetic nephropathy. Recently, a number of new agents have been described that have the potential to delay the progression of diabetic kidney disease and minimize the growing burden of end-stage renal disease. These include inhibitors and breakers of advanced glycation end products, receptor antagonists for advanced glycation end products, protein kinase C inhibitors, NADPH (reduced nicotinamide adenine dinucleotide phosphate) oxidase inhibitors, glycosaminoglycans, endothelin receptor antagonists, antifibrotic agents, and growth factor inhibitors. This review addresses these promising new therapeutic agents for delaying the progression of diabetic kidney disease.
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Affiliation(s)
- Faruk Turgut
- Division of Nephrology, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA
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