A RANDOMIZED CONTROLLED TRIAL OF THE DIRECT RENIN INHIBITOR ALISKIREN IN NON-DIABETIC CKD

Abstract

INTRODUCTION AND AIMS: Aliskiren as an add-on therapy to losartan further reduced proteinuria among patients with diabetic nephropathy, yet the ALTITUDE study designed to investigate the potential renal protection benefits using this combination was prematurely terminated due to increased adverse events in the aliskiren arm. The potential long-term efficacy of aliskiren in non-diabetic chronic kidney disease (CKD) is unknown. METHODS: This open-label, prospective, randomized, controlled trial investigated the renoprotective potential and safety of aliskiren added to an angiotensin II receptor blocker in non-diabetic CKD stages 3-4 patients in a University teaching hospital in Hong Kong. Eligible patients receiving an ARB at the maximal dose were randomly assigned aliskiren or conventional treatment to achieve BP under 130/80 mmHg. The coprimary outcomes were doubling of baseline serum creatinine (sCr) or a 40% reduction in estimated glomerular filtration rate (eGFR); and incident end-stage renal disease (ESRD). Secondary endpoints included cardiovascular events, hyperkalemia and death. RESULTS: 76 patients were randomized: 37 to aliskiren (27 male, mean age 55.0±11.1 y), and 39 to control (27 male, mean age 55.0±9.4 y). There was no difference in baseline demographics, sCr (194±61 vs. 215±65 μmol/l, P=0.15), eGFR (31.9±9.0 vs. 27.7±9.0 ml/min/1.73m2, P=0.05), and urine protein-to-creatinine ratio for treatment vs. control subjects. After a follow-up of 144 weeks, four patients in intervention group and seven patients in control group reached the composite endpoint of doubling of sCr or ESRD (10.8% vs. 18.0%, P=0.377). The number of cardiovascular events was 4 (10.8%) vs. 1 (2.6 %), P=0.147. Hyperkalemia was encountered in 7 (18.9%) vs. 2 (5.1%) patients (P=0.063). There was no difference in the rate of eGFR change or proteinuria between the 2 groups. CONCLUSIONS: Aliskiren conferred no additional renoprotective benefit nor increased adverse events except for more hyperkalemia in non-diabetic CKD patients.