EFFECTS OF MINERALOCORTICOID RECEPTOR ANTAGONISTS IN PROTEINURIC KIDNEY DISEASE

Abstract

Objective: Reductions in albuminuria of >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. Design and method: 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 to placebo or active treatment. Results: Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. Compared to placebo, MRAs 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 24hour 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 to calcium-channel-blockers (CCBs), while no differences were found compared to a second ACEi/ARB or other diuretics. Addition of an MRA was associated with change in estimated-glomerular-filtration-rate (eGFR) of −2.38 mL/min/1.73m2 (95%CI −3.51 to −1.25), rise in potassium by 0.22mEq/L (95%CI 0.16 to 0.28mEq/L) and a 2.5-fold increase in hyperkalemia risk (RR 2.63, 95%CI 1.69 to 4.08). Conclusions: Addition of MRAs confers an additive antiproteinuric effect in patients with CKD, with a slight increase in mean potassium levels.