ACE-I Lowers the Risk for Renal Disease in Obese Patients

Laurie Barclay, MD

Angiotensin converting enzyme (ACE) inhibition with the drug ramipril reduced the rate of renal events among patients with proteinuria in all body mass index (BMI) strata, but the effect was greater among obese patients, according to the results of a post hoc analysis published online April 28 in the Journal of the American Society of Nephrology.

"Obese patients with kidney disease progress more quickly towards renal failure compared to non-obese patients, and ramipril virtually abolishes this excess risk," senior author Carmine Zoccali, MD, from Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e di Immunologia Molecolare "Alberto Monroy," Palermo, and Ospedali Riuniti di Reggio Calabria in Italy, said in a news release.
The aim of this post hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) trial was to determine the effect of being overweight or obese on the incidence rate of renal events and on the response to ramipril among 337 REIN trial participants with known BMI. Overweight was present in 105 of these participants (31.1%), and obesity in 49 (14.5%).
Among participants randomly assigned to receive placebo, obese patients had a substantially higher incidence rate of end-stage renal disease (ESRD) than overweight patients (24 vs 11 events/100 person-years) or those with normal BMI (10 events/100 person-years). For the combined endpoint of ESRD or doubling of serum creatinine, findings were similar.
Among patients in all BMI strata, treatment with ramipril was associated with a lower rate of renal events. However, the effect of ramipril was more pronounced among obese participants (incidence rate reduction, 86% for ESRD and 79% for the combined endpoint) vs overweight participants (incidence rate reduction, 45% and 48%, respectively) or compared with participants who had a normal BMI (incidence rate reduction, 42% and 45%, respectively).
Analyses that adjusted for potential confounders confirmed this interaction between BMI and the efficacy of ramipril. BMI also had a similar influence on the efficacy of ramipril for 24-hour protein excretion.
"In summary, obesity predicts a higher incidence of renal events, but treatment with ramipril can essentially abolish this risk excess," the study authors write. "Furthermore, the reduction in risk conferred by ramipril is larger among obese than nonobese patients."
Limitations of this study include its post hoc analysis of a previous clinical trial, precluding definitive proof that ACE inhibitors have any selective effect. The findings also may not be generalizable to patients with lower levels of proteinuria or to racial/ethnic groups other than white Europeans.
"Obesity is now the most frequent cause of [chronic kidney disease]," Dr. Zoccali said. "In the United States, one out of four patients starting dialysis is obese.... Our findings strongly suggest that ACE inhibitors should be preferentially used in obese patients to prevent kidney disease moving to the most advanced stages."
A European Union grant supported this study. The study authors have disclosed no relevant financial relationships.
J Am Soc Nephrol.
Published online April 28, 2011. Abstract

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