Moderate antiproteinuric effect of add-on aldosterone blockade with eplerenone in non-diabetic chronic kidney disease. A randomized cross-over study

Abstract

Background: Reduction 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 design: Open randomized cross-over trial.

Setting and participants: Forty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/24 hours.

Intervention: Eight weeks of once-daily administration of add-on 25-50 mg eplerenone to stable standard antihypertensive treatment including RAS-blockade.

Outcomes & measurements: 24 hour urinary albumin excretion, BP, p-potassium, and creatinine clearance.

Results: The 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 Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia.

Limitations: Open label, no wash-out period and a moderate sample size.

Conclusions: In 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 registration: Clinicaltrials.gov NCT00430924.

Figure 1. Urinary albumin excretion.

Figure 1A illustrates albumin excretion during 8 weeks of add-on eplerenone as compared with control. Figure 1B illustrates the difference in urinary albumin excretion between treatment with eplerenone and control. Data are presented as mean values with 95% CI of the mean values. * P<0.05 for U-albumin excretion in the eplerenone period versus control period after Bonferroni correction. The difference in U-albumin excretion at week 4 versus week 8 in the eplerenone period was not significant. Note: N = number of urine samples.

Figure 2. P-potassium during 8 weeks of add-on eplerenone as compared with control.

Data are presented as mean values with 95% CI of the mean values.