IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria.
This European Community Biomedicine and Health Research-supported, multicenter, randomized, placebo-controlled, double-blind trial investigated the effect of an angiotensin-converting enzyme inhibitor (ACE-I) in children and young people with IgA nephropathy (IgAN), moderate proteinuria (>1 and <3.5 g/d per 1.73 m(2)) and creatinine clearance (CrCl) >50 ml/min per 1.73 m(2). Sixty-six patients who were 20.5 yr of age (range 9 to 35 yr), were randomly assigned to Benazepril 0.2 mg/kg per d (ACE-I) or placebo and were followed for a median of 38 mo. The primary outcome was the progression of kidney disease, defined as >30% decrease of CrCl; secondary outcomes were (1) a composite end point of >30% decrease of CrCl or worsening of proteinuria until > or =3.5 g/d per 1.73 m(2) and (2) proteinuria partial remission (<0.5 g/d per 1.73 m(2)) or total remission (<160 mg/d per 1.73 m(2)) for >6 mo. Analysis was by intention to treat. A single patient (3.1%) in the ACE-I group and five (14.7%) in the placebo group showed a worsening of CrCl >30%. The composite end point of >30% decrease of CrCl or worsening of proteinuria until nephrotic range was reached by one (3.1%) of 32 patients in the ACE-I group, and nine (26.5%) of 34 in the placebo group; the difference was significant (log-rank P = 0.035). A stable, partial remission of proteinuria was observed in 13 (40.6%) of 32 patients in the ACE-I group versus three (8.8%) of 34 in the placebo group (log-rank P = 0.033), with total remission in 12.5% of ACE-I-treated patients and in none in the placebo group (log-rank P = 0.029). The multivariate Cox analysis showed that treatment with ACE-I was the independent predictor of prognosis; no influence on the composite end point was found for gender, age, baseline CrCl, systolic or diastolic BP, mean arterial pressure, or proteinuria.
Coppo
Rosanna
R
Nephrology, Dialysis and Transplantation Unit, Regina Margherita University Hospital, 10127 Turin, Italy. nefrologia@oirmsantanna.piemonte.it
Peruzzi
Licia
L
Amore
Alessandro
A
Piccoli
Antonio
A
Cochat
Pierre
P
Stone
Rosario
R
Kirschstein
Martin
M
Linné
Tommy
T
D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005922:Glomerulonephritis, IGA / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010919:Placebos; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000188:drug therapy*; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D010919:Placebos; C044946:benazepril