Prospective randomized trial of effect of direct renin inhibition in non-diabetic chronic kidney disease (DRINK): an interim analysis

Abstract

BACKGROUND: Aliskiren reduces proteinuria among type 2 diabetics in the AVOID study. However, the ALTITUDE trial has been prematurely terminated on account of increased adverse events at 18-24 months in the aliskiren arm. We report the interim results of the DRINK study initiated in 2009 to investigate the renoprotective potential and safety of aliskiren added to maximum-dose angiotensin receptor blocker (ARB) in non-diabetic CKD stage 3-4 (eGFR 15-59ml/min/1.73 m2) patients, with a planned follow-up time of 3 years. METHODS: Eligible patients receiving an ARB were randomly assigned aliskiren (150 mg titrated up to 300 mg daily) or conventional antihypertensive treatment to achieve blood pressure under 130/80 mmHg. The primary outcome was the composite of a doubling of baseline serum creatinine (sCr), ESRD or death. Analysis was by intention to treat. RESULTS: Seventy-six patients were randomized: 37 to aliskiren (27 male, mean age 55.0±11.1 y), and 39 to control (27 male, mean age 55.1±9.4 y). There was no difference in baseline demographics, sCr (194±61 vs. 214±65 mmol/l, P=0.15), eGFR (31.9±9.0 vs. 28.0±9.0 ml/min/1.73m2, P=0.06), serum K+ (4.3±0.5 vs. 4.4±0.6 mmol/l, P=0.23) and urine protein-to-creatinine ratio (98.8±19.0 vs. 74.4±10.9 mg/mmol, P=0.26) between the treatment vs. control group. After a median follow-up of 96 weeks (IQR: 64-112), two patients in each group reached the composite endpoint of doubling of sCr or ESRD (5.4% vs. 5.1%, P=0.769). The number of cardiovascular events was 4 (10.8%) vs. 1 (2.5%), P=0.217. Hyperkalemia (serum K+ >5.5 mmol/l) was encountered in 7 (18.9%) vs. 2 (5.1%) patients (P=0.045), which was controlled with resin therapy without withdrawing the study medications. There was no difference in the change in proteinuria between the 2 groups. CONCLUSIONS: Our interim results demonstrated no significant increase in adverse events except for more hyperkalemia in aliskiren-treated non-diabetic CKD stage 3-4 patients. The DRINK study will continue as planned. Funding: partially from the Yu Professorship in Nephrology Endowment Fund.