Abstract P214: Meta-analysis of the Effect of Mineralocorticoid Receptor Antagonists on Proteinuria and Progression of Chronic Kidney Disease

Background/Objective: ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARB) are standard of care for patients with chronic kidney disease (CKD) and persistent proteinuria. Mineralocorticoid receptor (MR) activation has numerous “off target” effects on the kidney and vasculature and a number of studies have evaluated the use of MR antagonists (MRAs) in CKD. We conducted a meta-analysis of randomised controlled trials of MRA in addition to ACE-I and/or ARB in CKD to evaluate the potential reno-protective effects and risks of hyperkalaemia. Methods: MEDLINE (1966-2014) and EMBASE (1947-2014) were searched using a pre-specified strategy, and unpublished data were obtained from original study authors where possible (8 authors, 10 studies). Studies including dialysis or transplant patients and studies of less than 4 weeks duration were excluded from analysis. Results were pooled using random effects meta-analysis. Results: Eighteen trials (1438 patients) were included. Addition of MRA reduced blood pressure (-5.9, [95% CI 9.6, -2.2mmHg] for systolic; -2.3, [95% CI -3.6, -1.0mmHg] for diastolic) and weighted mean protein/albumin excretion (- 40.6%) at the cost of a small reduction in glomerular filtration rate (GFR) (-3.4, [95% CI -5.7, -1.1 ml/min/1.73m 2 ]). There was a 3-fold higher relative risk of hyperkalaemia above predefined trial limits (RR 3.21, [95% CI 1.19, 8.71]) equating to number needed to harm over one year of 23 [95% CI 7-267]. Average potassium increase was 0.21mmol/L [95% CI 0.08-0.33]. No studies reported life threatening hyperkalaemia events or hospitalisations as a result of hyperkalaemia. Baseline creatinine or diabetes status had no effect on hyperkalaemia risk in our analysis ( p =0.15 for creatinine; p =0.38 for diabetes status). Conclusion: Addition of MRA is a promising therapeutic strategy for reducing blood pressure and proteinuria in patients with CKD, with a quantifiable risk of hyperkalaemia. This reduction in proteinuria could translate into reduced risk of progressive renal disease and cardiovascular events but appropriately designed larger studies with long term follow up are required.