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

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.Open randomized cross-over trial.Forty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/24 hours.Eight weeks of once-daily administration of add-on 25–50 mg eplerenone to stable standard antihypertensive treatment including RAS-blockade.24 hour urinary albumin excretion, BP, p-potassium, and creatinine clearance.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 Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia.Open label, no wash-out period and a moderate sample size.In non-diabetic CKD patients, the addition of eplerenone to standard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

Antihypertensive Treatment and Renal Protection: the role of drugs inhibiting the renin-angiotensin-aldosterone system.

The prevalence of chronic kidney disease, currently estimated to vary between 8 and 12 % in the general population, is steadily rising due to aging and to the ongoing epidemic of hypertension and type 2 diabetes. Even in its early stages, chronic kidney disease entails a greater risk for cardiovascular mortality, and its prevention and treatment is rapidly becoming a key medical issue for many health care systems worldwide. Adequate blood pressure control and reduction of urine protein excretion, preferably obtained by the use of renin-angiotensin-aldosterone system inhibitors, have traditionally been considered the mainstay of therapeutic strategies in patients with renal disease. Given the pivotal role of renin-angiotensin-aldosterone system activity in the pathogenesis and progression of renal and cardiovascular damage, a more profound inhibition of the system, either by the use of multiple agents or by a single agent at high dosage has recently been advocated, especially in the presence of proteinuria. Recent trials, however have failed to confirm the usefulness of this therapeutic approach, at least in unselected patients. This article will critically review the current literature and will discuss the clinical implications of targeting the renin-angiotensin-aldosterone system in order to provide the greatest renal protection