Combination therapy with an ACE inhibitor and angiotensin-receptor blocker (ARB) is not more effective than an ARB alone in slowing renal disease progression in patients with diabetic nephropathy, but it is associated with an increased risk of acute kidney injury (AKI) and hyperkalemia, according to a recent study.

The multicenter, double-blind Veterans Affairs Nephropathy in Diabetes study included 1,448 patients with proteinuric diabetic kidney disease (urinary albumin-to-creatinine ratio of at least 300) and an estimated glomerular filtration rate (eGFR) of 30.0-89.9 mL/min/1.73 m2. The investigators, led by Linda F. Fried, MD, MPH, of the VA Pittsburgh Healthcare System in Pittsburgh, randomly assigned patients to receive the ARB losartan plus placebo or losartan plus the ACE inhibitor lisinopril. The patients had a median follow-up of 2.2 years. The primary endpoint was the first occurrence of a change in eGFR (a decline of 30 or more if the initial eGFR was 60 or greater or a decline of 50% or more if the initial eGFR was less than 60), end-stage renal disease, or death.

Primary endpoint events occurred in 152 (21%) of the 724 patients in the monotherapy arm and 132 (18.2%) of the 724 patients in the combination-therapy, a non-significant difference between the groups, the researchers reported in the New England Journal of Medicine (2013;369:1892-1903).

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Compared with the monotherapy arm, the combination-therapy arm had significantly higher rates of AKI (12.2 vs. 6.7 events per 100 person-years) and hyperkalemia (6.3 vs. 2.6 events per 100 person-years).

Additionally, the study found no significant between-group difference in the rate of cardiovascular events or death.