ACE inhibition is renoprotective among obese patients with proteinuria

Abstract

Obesity may increase the risk for progression of CKD, but the effect of established renoprotective treatments in overweight and obese patients with CKD is unknown. In this post hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, we evaluated whether being overweight or obese influences the incidence rate of renal events and affects the response to ramipril. Of the 337 trial participants with known body mass index (BMI), 105 (31.1%) were overweight and 49 (14.5%) were obese. Among placebo-treated patients, the incidence rate of ESRD was substantially higher in obese patients than overweight patients (24 versus 11 events/100 person-years) or than those with normal BMI (10 events/100 person-years); we observed a similar pattern for the combined endpoint of ESRD or doubling of serum creatinine. Ramipril reduced the rate of renal events in all BMI strata, but the effect was higher among the obese (incidence rate reduction of 86% for ESRD and 79% for the combined endpoint) than the overweight (incidence rate reduction of 45 and 48%, respectively) or those with normal BMI (incidence rate reduction of 42 and 45%, respectively). We confirmed this interaction between BMI and the efficacy of ramipril in analyses that adjusted for potential confounders, and we observed a similar effect modification 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. Furthermore, the reduction in risk conferred by ramipril is larger among obese than nonobese patients.

Figure 1.

Ramipril has no effect on the cumulative incidence of ESRD in normal BMI patients but markedly attenuates the risk of ESRD in overweight and obese patients. Crude, adjusted, and shrinkage-corrected hazard ratios and 95% confidence intervals of ramipril treatment for ESRD are reported in the insets.

Figure 2.

Ramipril prevents the rise in proteinuria which occurrs during follow-up in overweight and obese patients. Mean arterial pressure (top) and percent changes (follow-up versus baseline) in 24-hour urinary protein excretion (bottom) in ramipril (■)- and placebo (□)-treated patients across BMI categories. Data are mean ± SE.

Figure 3.

The anti-proteinuric effect of ramipril is maximal on obese patients and minimal in patients with normal BMI. Differences in urinary protein excretion (follow-up − baseline) are expressed as mean and SE. Data were adjusted for all variables listed in Table 3.