Among kidney transplant patients with proteinuria, the angiotensin-converting enzyme (ACE) inhibitor ramipril failed to reduce the risk of end-stage renal disease and death compared with placebo (Knoll GA et al. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(15)00368-X [published online October 22, 2015]). The unexpected trial findings stand in contrast to the benefits of ramipril for nontransplant patients with proteinuria. An accompanying editorial calls for a change in the international guidelines currently recommending ACE inhibitors as first-line treatment for transplant patients with proteinuria (Webster AC and Cross NB. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(15)00415-5 [published October 22, 2015]).
In the trial conducted in Canada and New Zealand, transplant recipients (N = 213) with an estimated glomerular filtration rate (GFR) of 20 mL/min/1.73 m2 or greater and proteinuria of 0.2 g/d or greater were randomly assigned to receive ramipril (5 mg orally twice daily) or placebo for up to 4 years. Patients completing the 4-year study were invited to participate in a trial extension of an average 48 months.
The primary outcome—doubling of serum creatinine, end-stage renal disease, or death— occurred in 17% of patients in the placebo group and 14% of patients in the ramipril group. In the extended 48-month follow-up, the primary outcome occurred in 25% in the placebo group and 24% of patients in the ramipril group. There was also no significant difference in measured GFR over time. Adverse events, which included a clinically significant reduction in hemoglobin level, were more common in the ramipril group (38%) than in the placebo group (22%).
A limitation of the study included failure to reach the target sample size due to physicians not being willing to discontinue ACE inhibitor use in their patients.