Public Release:  Reducing risk of renal failure in obese patients

American Society of Nephrology

The angiotensin-converting enzyme (ACE) inhibitor drug, ramipril, is particularly effective in lowering the risk of end-stage renal disease (ESRD) in obese patients, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN).

"Obese patients with kidney disease progress more quickly towards renal failure compared to non-obese patients, and ramipril virtually abolishes this excess risk," comments Carmine Zoccali, MD (CNR-IBIM and Ospedali Riuniti di Reggio Calabria, Italy).

The researchers analyzed data from a previous trial comparing ramipril with an inactive placebo in 337 patients with non-diabetes-related chronic kidney disease (CKD). Rates of progression to ESRD on the two treatments were compared in obese and overweight patients versus normal-weight patients.

On placebo, the risk of developing ESRD was more than twice as high for obese patients compared to normal-weight patients: 24 versus 10 per 100 person-years. For patients who were overweight but not obese, ESRD risk was similar to that in normal-weight patients.

Ramipril lowered the risk of progression to ESRD in all three weight groups. However, the magnitude of risk reduction was much greater for obese patients: 86 percent, compared to 45 percent in normal-weight patients. Thus, obese patients taking ramipril exhibited about the same ESRD risk as normal-weight patients.

"Obesity is now the most frequent cause of CKD," according to Zoccali. "In the United States, one out of four patients starting dialysis is obese." Ramipril and other ACE inhibitors are frequently used to treat CKD in patients with high levels of protein in the urine (proteinuria), like the ones in the study.

"Our findings strongly suggest that ACE inhibitors should be preferentially used in obese patients to prevent kidney disease moving to the most advanced stages," Zoccali concludes. He calls for further analyses to confirm the results, as well as new trials specific to obese patients with CKD.

As a new analysis of a previous clinical trial, the study cannot be considered as definitive proof that ACE inhibitors have any special impact in obese patients with CKD. In addition, the study focused on kidney disease associated with high levels of proteinuria; it's unknown whether ACE inhibitors will have the same protective effect in patients with lower levels of proteinuria. Furthermore, the patients were all white Europeans; the results need to be confirmed in studies including other ethnicities.

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The authors reported no financial disclosures.

Study co-authors were Francesca Mallamaci, MD, Piero Ruggenenti, MD, Annalisa Perna, Stat SciD, Daniela Leonardis MD, Rocco Tripepi, Giovanni Tripepi, Stat SciD, and Giuseppe Remuzzi, MD. Drs. Ruggenenti, Perna, and Remuzzi are at Mario Negri Institute for Pharmacological Research, Bergamo, Italy. Drs. Remuzzi and Ruggenenti were the leaders of the Ramipril Efficacy in Nephropathy (REIN) study, the primary source of data for the new study.

The article, entitled "ACE Inhibition Is Renoprotective among Obese Patients with Proteinuria" will appear online at http://jasn.asnjournals.org/ on April 28, 2011, doi 10.1681/ASN.2010090969.

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