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    Study: ACE Inhibitors -- a Type of Blood Pressure Drug -- Slow the Progression of Kidney Disease

    End-stage renal disease (ESRD) is the medical term for kidney failure, and its only treatments are dialysis or kidney transplant. The most common cause of ESRD is diabetes, and it has been shown that treatment of diabetics with ACE inhibitors, a type of drug originally used to treat high blood pressure, can prevent the progression of diabetic kidney disease to ESRD. A new study appearing in the July 17th issue of the Annals of Internal Medicine gives evidence to support the use of ACE-inhibitors (ACEI) as a preventive agent against kidney failure in patients with non-diabetic kidney disease as well.

    Over 350,000 people in the U.S. have chronic kidney failure, or ESRD, and require dialysis or transplantation to survive. Those who require dialysis have an annual mortality (death) rate of 20% to 25%. The data found in the current study was accumulated from an analysis of 11 separate controlled clinical trials of various medications used in the treatment of chronic kidney diseases which might lead to kidney failure. The authors came from an international group, led by Tazeem Jafar, M.D., M.P.H., of the New England Medical Center-Tufts University School of Medicine, in Boston.

    The analysis involved studies of 1860 patients, with 941 in the groups receiving ACEI therapy, and 919 patients who did not get ACEI drugs, the control group. All participants who entered the study had a history of high blood pressure or decreased kidney function. Those who had previously been treated with ACEIs were switched to alternative medications for at least three weeks prior to the study outset. The control subjects received either placebo or other types of blood pressure drugs. The outcomes measured were the occurrence of ESRD (defined by the start of dialysis), or a twofold worsening of serum creatinine, a common blood waste product which reflects kidney function.

    A total of 1131 patients completed the studies. The average duration of follow-up was 2.2 years. Significantly fewer patients in the ACEI group developed ESRD (7.4%) than in the control group (11.6%). This represents a 36% benefit in the ACEI group. When the combination result of either ESRD or doubling of the serum creatinine was evaluated, the ACEI group had a rate of 13.2% for either of these events, as compared to the control group’s 20.5%, a 35% improvement in outlook. On further analysis, the beneficial effect of ACEIs on kidney function was found to be separate from, and additional to, their effects on blood pressure.

    The authors state, "Our pooled analysis of data from 11 randomized, controlled trials reveals strong and consistent effects of ACEIs in slowing the progression of nondiabetic renal disease…Our findings have important implications for the use of ACEIs in clinical practice…Chronic renal insufficiency is underdiagnosed and undertreated in the U.S., and opportunities for the prevention of ESRD are lost. Our results show that [blood pressure] regimens including ACEIs are more effective than regimens not including ACEIs in slowing the progression of nondiabetic renal disease. Therefore, we conclude that ACEIs should be the [blood pressure] agents of first choice in nondiabetic renal disease, as they are in diabetic renal disease."

    An editorial in the same journal, by Robert Schrier M.D. and Raymond Estacio M.D. of the University of Colorado Health Sciences Center, cautions that "meta-analyses [pooled analyses of several different studies] cannot produce definitive conclusions." They also point out that 5 out of the 11 studies "compared ACEIs with [inactive] placebo," thus making it "difficult to determine whether the same results would have occurred if the ACEI groups were compared instead with a pooled group of persons receiving active [blood pressure] therapy." They conclude that the study results "must be considered tentative" as an "exciting hypothesis that warrants confirmation."



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