Despite its widespread use, the ACE inhibitor ramipril does not appear to prevent transplant failure or death in kidney transplant patients with proteinuria, a new study finds.
“Current guidelines make an ungraded recommendation that ACE inhibitors or ARBs be considered as first-line antihypertensives in transplant patients with proteinuria,” investigators led by Greg A. Knoll, MD, and Dean Fergusson, PhD, of the University of Ottawa in Canada, explained in The Lancet Diabetes-Endocrinology. “The data from our trial suggests that ramipril use in transplant patients with proteinuria is associated with more adverse events and probably no significant improvement in clinical outcomes. Treatment guidelines should be reconsidered given the findings of our trial.”
For the double-blind trial, the investigators randomly assigned 213 kidney transplant recipients from 14 centers in Canada and New Zealand to ramipril (5 mg twice daily) or placebo for up to 4 years. The recipients’ estimated glomerular filtration rate (eGFR) was at least 20 mL/min/1.73m2 and proteinuria 0.2 g per day or above.
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Within 4 years, 17% of patients taking placebo and 14% taking ramipril experienced a composite endpoint of a doubling of serum creatinine, end-stage renal disease, and early death. After an extended follow-up of an additional 4 years on average, the endpoint occurred in 25% of the placebo group and 24% of the ramipril group. The absolute difference was only 0.5% between groups. Ramipril did not lead to a significant reduction, the researchers concluded.
The researchers observed no significant difference in eGFR decline between groups. Ramipril showed no benefit on renal function. Adverse events, however, were more common among patients taking ramipril than placebo.
These results are particularly notable because these patients were at high-risk for renal failure or death: 43% had diabetes, 67% had hyperlipidemia, 25% had a history of cardiovascular disease, and 43% had substantial proteinuria (above 500 mg per day). Overall, 14% of the ramipril group and 10% of the placebo group died.
Despite evidence to support the use of ACE inhibitors in non-transplant patients with proteinuria, the drugs do not appear to benefit kidney transplant patients, the researchers stated.
Among the study limitations, they noted that a larger dose of ramipril (above 10 mg daily) might have shown a clinical benefit. The cause of proteinuria also could be an important factor.
Future trials should focus on particular transplant patients, such as those with recurrent glomerulonephritis, to determine whether ACE inhibitors help these populations, they suggested.
