By Colin Kenny, GP, County Down
We know that the angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) individually are renoprotective for people with diabetes who have diabetic nephropathy and that combining the therapies produces a greater reduction in urinary protein excretion. The recently published Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) study compared the combination of losartan plus lisinopril with losartan alone in people with diabetes who had proteinuria in a double-blind randomised controlled trial.
Participants in this study had type 2 diabetes, an estimated glomerular filtration rate of 30–89.9 mL/min/1.73 m2, and a urinary albumin-to-creatinine ratio of at least 300 µg/mg. A total of 1448 participants were initiated on losartan. Once individuals were on a stable dose they were randomly assigned to receive either lisinopril (up to 40 mg daily) or placebo in a 1:1 ratio. Combination therapy increased the risk of hyperkalaemia and also increased the risk of acute kidney injury. There was no mortality benefit with combination therapy, and the study was ultimately stopped early owing to safety issues, given the results of the combination therapy group. This study demonstrates that the lack of benefit, along with significant adverse effects of combined therapy, do not justify this combination in people with diabetes who have proteinuria.
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