P Zucchelli

BACKGROUND: Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases. METHODS: In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis. RESULTS: At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with 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 benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group. CONCLUSIONS: Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.

Sixty-seven adults with idiopathic membranous nephropathy and the nephrotic syndrome were randomly assigned to symptomatic treatment only or to a six-month course of methylprednisolone alternated with chlorambucil every other month. Patients were followed for one to seven years. At the end of follow-up (mean of 31.4 +/- 18.2 months for the treated group and 37.0 +/- 22.0 for the control group) 23 of 32 treated patients were in complete or partial remission, as compared with 9 of 30 control patients (P = 0.001). Twelve of the treated patients were in complete remission, as compared with only two of the controls. In the treated group there were no changes in renal function during follow-up, whereas in the control group the reciprocal of the plasma creatinin level, which is proportional to the creatinine clearance, decreased significantly (P = 0.00017) after two years of follow-up. Side effects were minimal in all treated patients except two, who were dropped from the study because of peptic ulcer and gastric intolerance to chlorambucil. We conclude that steroid and chlorambucil treatment for six months favors remission of the nephrotic syndrome in adults with idiopathic membranous nephropathy and can preserve renal function for at least some years.