Effect of the Angiotensin-Converting-Enzyme Inhibitor Benazepril on the Progression of Chronic Renal Insufficiency

doi:10.1056/NEJM199604113341502

Volume 334:939-945		April 11, 1996		Number 15

Effect of the Angiotensin-Converting–Enzyme Inhibitor Benazepril on the Progression of Chronic Renal Insufficiency

Giuseppe Maschio, M.D., Daniele Alberti, M.D., Gérard Janin, M.D., Francesco Locatelli, M.D., Johannes F.E. Mann, M.D., Mario Motolese, M.D., Claudio Ponticelli, M.D., Eberhard Ritz, M.D., Pietro Zucchelli, M.D., for The Angiotensin-Converting–Enzyme Inhibition in Progressive Renal Insufficiency Study Group

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ABSTRACT

Background Drugs that inhibit angiotensin-converting enzymeslow the progression of renal insufficiency in patients withdiabetic nephropathy. Whether these drugs have a similar actionin patients with other renal diseases is not known. We conducteda study to determine the effect of the angiotensin-converting–enzymeinhibitor benazepril on the progression of renal insufficiencyin patients with various underlying renal diseases.

Methods In a three-year trial involving 583 patients with renalinsufficiency caused by various disorders, 300 patients receivedbenazepril and 283 received placebo. The underlying diseasesincluded glomerulopathies (in 192 patients), interstitial nephritis(in 105), nephrosclerosis (in 97), polycystic kidney disease(in 64), diabetic nephropathy (in 21), and miscellaneous orunknown disorders (in 104). The severity of renal insufficiencywas classified according to the base-line creatinine clearance:227 patients had mild insufficiency (creatinine clearance, 46to 60 ml per minute), and 356 had moderate insufficiency (creatinineclearance, 30 to 45 ml per minute). The primary end point wasa doubling of the base-line serum creatinine concentration orthe need for dialysis.

Results At three years, 31 patients in the benazepril groupand 57 in the placebo group had reached the primary end point(P<0.001). In the benazepril group, the reduction in therisk of reaching the end point was 53 percent overall (95 percentconfidence interval, 27 to 70 percent), 71 percent (95 percentconfidence interval, 21 to 90 percent) among the patients withmild renal insufficiency, and 46 percent (95 percent confidenceinterval, 12 to 67 percent) among those with moderate renalinsufficiency. The reduction in risk was greatest among themale patients; those with glomerular diseases, diabetic nephropathy,or miscellaneous or unknown causes of renal disease; and thosewith base-line urinary protein excretion above 1 g per 24 hours.Benazepril was not effective in patients with polycystic disease.Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazeprilgroup and increased by 0.2 to 1.5 mm Hg in the placebo group.

Conclusions Benazepril provides protection against the progressionof renal insufficiency in patients with various renal diseases.

Source Information

From the Divisione di Nefrologia, Ospedale Civile, Verona, Italy (G.M.); the Medical Department, Ciba–Geigy, Origgio, Italy (D.A., M.M.); the Service d'Hémodialyse, Hôpital des Chanaux, Mâcon, France (G.J.); the Divisione di Nefrologia, Ospedale di Lecco, Lecco, Italy (F.L.); the VI Medizinische Abteilung, Staedtisches Klinikum Schwabing, and the German Institute for High Blood Pressure Research, Munich, Germany (J.F.E.M.); the Divisione di Nefrologia e Dialisi, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Maggiore Policlinico, Milan, Italy (C.P.); the Rehabilitationszentrum für Chronisch Nierenkranke, Universitätsklinik Heidelberg, Heidelberg, Germany (E.R.); and the Divisione di Nefrologia e Dialisi, Servizio Ospedaliero S. Orsola, Malpighi, Bologna, Italy (P.Z.).

Address reprint requests to Dr. Maschio at the Divisione di Nefrologia, Ospedale Civile, I-37126, Verona, Italy.

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Effect of Benazepril in Chronic Renal Insufficiency
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N Engl J Med 1996; 335:596-598, Aug 22, 1996. Correspondence

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