Overweight and Obesity Strong Risks for Renal Disease

Obesity, a major pubic health problem worldwide, is a risk factor for renal disease, operating through several mechanisms, most notably inflammatory cytokines. Speaking on the topic of obesity and chronic kidney disease, Francesca Mallamaci, MD, of the Institute of Biomedicine, Division of Nephrology in Reggio Calabria, Italy, presented evidence that inflammatory mechanisms and alterations in renal hemodynamics largely overlap.

ACE inhibition may be a good way to preserve kidney function as overweight and obese individuals have been found to be particularly sensitive to the renoprotective effects of ramipril.

In her review of the subject, Mallamaci showed that as body mass index (BMI) increases, so does the risk of chronic kidney disease (CKD). The largest study on the topic was a survey of a multiracial general population in the United States, where the prevalence of overweight and obesity is near 40 percent.

Compared with a non-overweight BMI of up to 24.9 kg/m2, CKD risk increases steadily with weight, tripling for a BMI in the range of 25.0–29.9 kg/m2, and reaching a sevenfold higher risk once the BMI is at or above 40.0 kg/m2.

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Inflammatory cytokines, especially interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), likely contribute to vascular dysfunction at the level of the glomerulus and cause renal damage. Procalcitonin is a relatively newly described inflammatory marker, and its concentration increases with each increasing quartile of waist circumference, “a phenomenon implicating inflammation in obesity-related CKD,” Mallamaci said.

Mallamaci noted that renal plasma flow declines with increasing body weight before reaching outright obesity. Glomerular filtration rate (GFR) does not decrease concomitantly at this point, and glomerular hyperfiltration occurs in the early stages of overweight. This hyperfiltration contributes to the eventual loss of renal function.

From a post hoc analysis of results of the Ramipril Efficacy in Nephropathy (REIN) study, obesity was a strong predictor of renal events.

The more that weight increased, the more effective ramipril was in reducing proteinuria compared to placebo. It also reduced the incidence rate of ESRD more at higher BMIs.

Mallamaci proposed that ramipril exerts its renoprotective effect in the overweight/obese population by reducing glomerular efferent vasoconstriction, thereby transiently reducing the GFR, thus reducing the deleterious hyperfiltration.

She said no controlled trial testing the effect of weight loss on renal disease progression has ever been done, and she doubts one ever will be. For the future, she advocated performing randomized clinical trials specifically designed to look at possible protective effects of ACE inhibitors in preventing renal events in this patient population, but these, too, are doubtful. So she suggested further post hoc analysis of existing trials, as was done with REIN.