Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial.

BACKGROUND: Recent studies have shown that both steroids and angiotensin-converting enzyme (ACE) inhibitors improve kidney survival and decrease proteinuria in patients with immunoglobulin A nephropathy. In this study, we aim to investigate whether the addition of steroids to ACE-inhibitor therapy produces a more potent antiproteinuric effect and better protection of kidney function than an ACE inhibitor alone.

STUDY DESIGN: Randomized controlled trial.

SETTING & PARTICIPANTS: Patients with biopsy-proven immunoglobulin A nephropathy with proteinuria of 1 to 5 g/d of protein.

INTERVENTION: 63 patients were randomly assigned to either cilazapril alone (ACE-inhibitor group; n = 30) or steroid plus cilazapril (combination group; n = 33).

OUTCOMES & MEASUREMENTS: The primary end point was kidney survival, defined as a 50% increase in baseline serum creatinine level.

RESULTS: After follow-up for up to 48 months, 7 patients in the ACE-inhibitor group (24.1%) reached the primary end point compared with 1 patient (3%) in the combination group. Kaplan-Meier kidney survival was significantly better in the combination group than the ACE-inhibitor group after 24 and 36 months (96.6% versus 75.7%, 96.6% versus 66.2%; P = 0.001). Urine protein excretion significantly decreased in patients in the combination group compared with the ACE-inhibitor group (time-average proteinuria, 1.04 +/- 0.54 versus 1.57 +/- 0.86 g/d of protein; P = 0.01). Multivariate analysis showed that combination treatment (hazard ratio, 0.1; 95% confidence interval, 0.014 to 0.946) and time-average proteinuria (hazard ratio, 14.3; 95% confidence interval, 2.86 to 71.92) were independent predictors of kidney survival.

LIMITATIONS: Small sample size, a single center, and slight imbalances at baseline.

CONCLUSIONS: Our results suggest that the addition of steroid to ACE-inhibitor therapy provided additional benefit compared with an ACE inhibitor alone. However, this was a pilot study with a small number of participants achieving the end points, and thus further validation is necessary.