Moderate Antiproteinuric Effect of Add-On Aldosterone Blockade with Eplerenone in Non-Diabetic Chronic Kidney Disease. A Randomized Cross-Over Study

Abstract

BackgroundReduction of proteinuria and blood pressure (BP) with blockers of the renin-angiotensin system (RAS) impairs the progression of chronic kidney disease (CKD). The aldosterone antagonist spironolactone has an antiproteinuric effect, but its use is limited by side effects. The present study evaluated the short-term antiproteinuric effect and safety of the selective aldosterone antagonist eplerenone in non-diabetic CKD.Study DesignOpen randomized cross-over trial.Setting and ParticipantsForty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/24 hours.InterventionEight weeks of once-daily administration of add-on 25–50 mg eplerenone to stable standard antihypertensive treatment including RAS-blockade.Outcomes & Measurements24 hour urinary albumin excretion, BP, p-potassium, and creatinine clearance.ResultsThe mean urinary albumin excretion was 22% [CI: 14,28], P<0.001, lower during treatment with eplerenone. Mean systolic BP was 4 mmHg [CI: 2,6], P = 0.002, diastolic BP was 2 mmHg [CI: 0,4], P = 0.02, creatinine clearance was 5% [CI: 2,8], P = 0.005, lower during eplerenone treatment. After correction for BP and creatinine clearance differences between the study periods, the mean urinary albumin excretion was 14% [CI: 4,24], P = 0.008 lower during treatment. Mean p-potassium was 0.1 mEq/L [CI: 0.1,0.2] higher during eplerenone treatment, P<0.001. Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia.LimitationsOpen label, no wash-out period and a moderate sample size.ConclusionsIn non-diabetic CKD patients, the addition of eplerenone to standard antihypertensive treatment including RAS-blockade caused a moderate BP independent fall in albuminuria, a minor fall in creatinine clearance and a 0.1 mEq/L increase in p-potassium.Trial RegistrationClinicaltrials.gov NCT00430924

Successful Treatment with an Antihypertensive Drug Regimen Including Eplerenone in a Patient with Malignant Phase Hypertension with Renal Failure

“…Several clinical studies have confirmed the antialbuminuric effects of MR antagonists given in addition to ACE-Is or ARBs in patients with diabetes or CKD (15,16). In the present patient, the urinary albumin level decreased during the clinical course.…”

Cardiovascular actions of mineralocorticoid receptor antagonists in patients with chronic kidney disease: A systematic review and meta-analysis of randomized trials

“…One study examined patients on peritoneal dialysis, 39 two studies examined patients on haemodialysis 38,42 and the remaining studies examined patients with CKD. All but two 14,16 of these studies excluded patients with advanced CKD (estimated GFR<30 ml/min per 1.73 m 2 ) although it was not clear how many patients with this level of renal function were actually recruited. We did not identify any eligible study involving renal transplant recipients.…”

Mineralocorticoid Receptor Antagonist for Renal Protection

“…For nondiabetic CKD, a recent randomized crossover study of 40 patients found that adding EPL for 8 weeks to the standard antihypertensive treatment (including RAS blockade) resulted in 22% reduction in albuminuria, with only a modest effect on blood pressure and renal function. 37 The ongoing EVALUATE study is another double-blinded, randomized, placebo-controlled trial, which evaluates the antiproteinuric effect of EPL 50 mg daily in 340 hypertensive patients with albuminuria and would provide further insight in this respect. 38 …”