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ACE inhibitors, when included in an antihypertensive regimen, slow progression of nondiabetic renal disease

Chronic renal disease, often due to hypertension, is a major public health problem in the United States, with an estimated 357,000 people suffering from end-stage renal disease (ESRD) in 1999. The annual cost of treatment with dialysis and renal transplantation is nearly $16 billion. Patients undergoing dialysis have a reduced quality of life, a high rate of illness, and an annual mortality rate of 20 to 25 percent.

Findings from a recent study indicate that angiotensin-converting enzyme (ACE) inhibitors should be the antihypertensive agents of first choice in slowing progression of nondiabetic renal disease, as they are in patients who have diabetes and renal disease. The study was led by Christopher H. Schmid, Ph.D., and Andrew S. Levey, M.D., of the New England Medical Center, and supported in part by the Agency for Healthcare Research and Quality (HS08532 and HS10064). The researchers did a meta-analysis of 11 randomized controlled studies on 1,860 patients with nondiabetic renal disease to compare the efficacy of antihypertensive regimens with and without ACE inhibitors.

After a mean of 2.2 years, patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg and 2.3 mm Hg, respectively) and urinary protein excretion (0.46 g/d) than those in the non-ACE inhibitor group. Excessive urinary protein excretion (proteinuria) is an indicator of poor kidney functioning. After adjusting for patient differences and study characteristics, the ACE inhibitor group had nearly one-third less likelihood of developing ESRD or both doubling the baseline concentration of serum creatinine (which indicates progression of renal disease) or developing ESRD. This effect persisted even after adjusting for changes in blood pressure and urine protein during followup.

Significantly fewer patients in the ACE inhibitor group than in the control group developed ESRD (7.4 vs. 11.6 percent), had either a doubling of baseline serum creatinine or ESRD (13.2 vs. 20.5 percent), or had a combined outcome of ESRD or death (9.6 vs. 12.8 percent). Patients with proteinuria at baseline (0.5 g/d or more; normal is less than 0.5 g/d) benefited more from ACE inhibitor therapy than others. The researchers conclude that ACE inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria. The beneficial effect also appears to involve factors other than just the blood pressure and urine protein-lowering effects.

For more details, see "Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: A meta-analysis of patient-level data," by Tazeen H. Jafar, M.D., M.P.H., Dr. Schmid, Marcia Landa, M.A., and others, in the July 17, 2001 Annals of Internal Medicine 135(2), pp. 73-87.

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