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

Am J Kidney Dis. 2009 Jan;53(1):26-32. doi: 10.1053/j.ajkd.2008.07.029. Epub 2008 Oct 19.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00378443.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biopsy
  • Cilazapril / adverse effects
  • Cilazapril / therapeutic use*
  • Creatinine / blood
  • Drug Therapy, Combination
  • Female
  • Glomerulonephritis, IGA / blood
  • Glomerulonephritis, IGA / drug therapy*
  • Glomerulonephritis, IGA / physiopathology
  • Humans
  • Kidney / pathology
  • Kidney / physiopathology
  • Male
  • Multivariate Analysis
  • Outcome Assessment, Health Care
  • Pilot Projects
  • Prednisone / adverse effects
  • Prednisone / therapeutic use*
  • Proteinuria / blood
  • Proteinuria / drug therapy
  • Proteinuria / physiopathology
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Angiotensin-Converting Enzyme Inhibitors
  • Cilazapril
  • Creatinine
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT00378443