BackgroundHypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease.MethodsWe conducted a meta-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966–2014), EMBASE (1947–2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators. We included randomised controlled trials, and the first period of randomised cross over trials lasting ≥4 weeks in adults.ResultsNineteen trials (21 study groups, 1 646 patients) were included. In random effects meta-analysis, addition of mineralocorticoid receptor antagonists to renin angiotensin system inhibition resulted in a reduction from baseline in systolic blood pressure (−5.7 [−9.0, −2.3] mmHg), diastolic blood pressure (−1.7 [−3.4, −0.1] mmHg) and glomerular filtration rate (−3.2 [−5.4, −1.0] mL/min/1.73 m2). Mineralocorticoid receptor antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a threefold higher relative risk of withdrawing from the trial due to hyperkalaemia (3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were not reported in sufficient numbers to analyse.ConclusionsMineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0337-0) contains supplementary material, which is available to authorized users.

BackgroundPatients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity associated with increased arterial stiffness. Plasma aldosterone levels are increased in CKD, and aldosterone has been found to increase vascular inflammation and fibrosis. It was hypothesized that aldosterone receptor inhibition with eplerenone could reduce arterial stiffness in CKD stage 3–4.Study DesignThe design was randomized, open, parallel group. Measurements of arterial stiffness markers were undertaken at weeks 1 and 24.Intervention24 weeks of add-on treatment with 25–50 mg eplerenone or standard medication.OutcomesPrimary outcome parameter was carotid-femoral pulse wave velocity (cfPWV). Secondary outcomes were augmentation index (AIx), ambulatory arterial stiffness index (AASI) and urinary albumin excretion.ResultsFifty-four CKD patients (mean eGFR 36 mL/min/1.73 m2, SD 11) were randomized. Forty-six patients completed the trial. The mean difference in cfPWV changes between groups was 0.1 m/s (95%CI: −1.0, 1.3), P = 0.8. The mean difference in AIx changes between groups was 4.4% (0.1, 8.6), P = 0.04. AASI was unchanged in both groups. The ratio of change in urinary albumin excretion in the eplerenone group compared to the control was 0.61 (0.37, 1.01), P = 0.05. Four patients were withdrawn from the eplerenone group including three because of possible side effects; one was withdrawn from the control group. Mild hyperkalemia was seen on three occasions and was easily managed.LimitationsThe full planned number of patients was not attained. The duration of the trial may have been too short to obtain full effect of eplerenone on the arteries.ConclusionsAdd-on treatment with eplerenone in CKD stage 3–4 did not significantly reduce cfPWV. There may be beneficial vascular effects leading to attenuated pulse wave reflection. Treatment was well-tolerated.Trial Registration ClinicalTrials.gov NCT01100203

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