Maria-Eleni Alexandrou1,2, Aikaterini Papagianni2, Apostolos Tsapas3, Charalampos Loutradis2, Afroditi Boutou4, Alexia Piperidou5, Dorothea Papadopoulou1, Luis Ruilope6, George Bakris7, Pantelis Sarafidis2. 1. Department of Nephrology, Papageorgiou Hospital. 2. Department of Nephrology, Aristotle University of Thessaloniki, Hippokration Hospital. 3. Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki. 4. Department of Respiratory Medicine, Papanikolaou Hospital. 5. 2nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki Hospital General Hippokration, Thessaloniki, Greece. 6. Institute of Research i+12, Hospital Universitario 12 de Octubre, and School of Doctoral Studies and Research, Universidad Europea de Madrid, Madrid, Spain. 7. Department of Medicine, American Society of Hypertension Comprehensive Hypertension Center, The University of Chicago Medicine, Chicago, Illinois, USA.
Abstract
BACKGROUND: Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin-angiotensin system (RAS) blockade represents the cornerstone of CKD treatment. However, as CKD progression still occurs, other nephroprotective options were explored; mineralocorticoid receptor antagonists (MRA) were tested with generally positive results. METHODS: We conducted a systematic review and meta-analysis on the effects of MRAs on albuminuria/proteinuria, and adverse events, such as change in renal function and hyperkalemia incidence. A detailed search in electronic databases, clinical trial registries and grey literature was performed to retrieve randomized controlled trials (RCTs) in which administration of an MRA alone or on-top of ACEi/ARB was compared with placebo or active treatment. RESULTS: Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. The use of MRAs (alone or on top of RAS blockade) compared with placebo decreased urine albumin-to-creatinine ratio (UACR) by -24.55% (95% CI -29.57 to -19.53%), urine protein-to-creatinine ratio (UPCR) by -53.93% (95% CI -79% to -28.86%) and 24 h albumin excretion by -32.47% (95% CI -41.1 to -23.85%). MRAs also reduced UACR by -22.48% (95% CI -24.51 to -20.44%) compared with calcium-channel-blockers (CCBs), whereas no differences were found compared with a second ACEi/ARB or nonpotassium-sparing diuretics. Addition of an MRA was associated with change in estimated glomerular filtration rate (eGFR) of -2.38 ml/min per 1.73 m (95% CI -3.51 to -1.25), rise in potassium by 0.22 mEq/l (95% CI 0.16-0.28 mEq/l) and a 2.6-fold increase in hyperkalemia risk (RR 2.63, 95% CI 1.69-4.08) compared with placebo/active control. CONCLUSION: Use of MRAs alone or on top of RAS blockade confers important antiproteinuric effects in patients with CKD, with a slight increase in mean potassium levels.
BACKGROUND: Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin-angiotensin system (RAS) blockade represents the cornerstone of CKD treatment. However, as CKD progression still occurs, other nephroprotective options were explored; mineralocorticoid receptor antagonists (MRA) were tested with generally positive results. METHODS: We conducted a systematic review and meta-analysis on the effects of MRAs on albuminuria/proteinuria, and adverse events, such as change in renal function and hyperkalemia incidence. A detailed search in electronic databases, clinical trial registries and grey literature was performed to retrieve randomized controlled trials (RCTs) in which administration of an MRA alone or on-top of ACEi/ARB was compared with placebo or active treatment. RESULTS: Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. The use of MRAs (alone or on top of RAS blockade) compared with placebo decreased urine albumin-to-creatinine ratio (UACR) by -24.55% (95% CI -29.57 to -19.53%), urine protein-to-creatinine ratio (UPCR) by -53.93% (95% CI -79% to -28.86%) and 24 h albumin excretion by -32.47% (95% CI -41.1 to -23.85%). MRAs also reduced UACR by -22.48% (95% CI -24.51 to -20.44%) compared with calcium-channel-blockers (CCBs), whereas no differences were found compared with a second ACEi/ARB or nonpotassium-sparing diuretics. Addition of an MRA was associated with change in estimated glomerular filtration rate (eGFR) of -2.38 ml/min per 1.73 m (95% CI -3.51 to -1.25), rise in potassium by 0.22 mEq/l (95% CI 0.16-0.28 mEq/l) and a 2.6-fold increase in hyperkalemia risk (RR 2.63, 95% CI 1.69-4.08) compared with placebo/active control. CONCLUSION: Use of MRAs alone or on top of RAS blockade confers important antiproteinuric effects in patients with CKD, with a slight increase in mean potassium levels.
Authors: Rajiv Agarwal; Patrick Rossignol; Jeffrey Budden; Martha R Mayo; Susan Arthur; Bryan Williams; William B White Journal: Kidney360 Date: 2021-01-15
Authors: Frédéric Jaisser; Xiaojuan Tan; Shuangshuang Chi; Jinrong Liu; Ping Wang; Mark Bush; Vincent Benn; Y Fred Yang; Jay Zhang Journal: Front Pharmacol Date: 2021-06-24 Impact factor: 5.810