ACE inhibitor renal benefits do not translate to transplants

Beneficial effects of ACE inhibitors on renal function in patients with proteinuria do not translate to kidney transplant recipients, according to results from the first placebo-controlled, randomised controlled trial to address the issue.

A Canadian and New Zealand research team randomised 213 transplant recipients with proteinuria of 0.2 g/day or more to ramipril 5 mg/day or placebo for four years, followed by an extension phase.

The primary outcome, a composite of doubling of serum creatinine, end-stage renal disease or death, occurred in 14% of the ramipril group and 17% of the placebo group, but the difference was not statistically significant.

There were also no significant differences in the rate of decline in GFR or in mortality.

“These results do not support the use of ACE inhibitors with the goal of improving clinical outcomes in this population,” they concluded.

Writing in Lancet Diabetes & Endocrinology, they said that even if a treatment effect was present, its likely impact would be small.

An editorial co-authored by Associate Professor Angela Webster, a nephrologist and transplant physician at Westmead Hospital in Sydney, and Christchurch nephrologist Dr Nick Cross, stressed the need for caution in assuming that clinical trial results from one group of patients could be generalised to others.

“ACE inhibitors have been shown to be effective in reducing proteinuria, progression of kidney disease and death in non-transplant populations with proteinuria,” they said.

“It is tempting therefore to assume that kidney transplant recipients with proteinuria would also benefit from ACE inhibitors.”

They noted the difficulties in conducting the study, including slow recruitment and the release, while the trial was running, of international guidelines recommending the use of ACE inhibitors in these patients.

“The results of this trial should change these guidelines, but whether change in practice will follow is less clear,” they said.

The study protocol required tight blood pressure management using agents other than ACE inhibitors, in addition to the study drugs.

Although those randomised to ramipril more often achieved the target of <130/80 mmHg, control was generally good, which might have explained why there was relatively little difference in outcomes.

Use of a 5 mg rather than 10 mg dose of ramipril might also have limited the benefits of the ACE inhibitor, they added.

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