Long-term results of a randomized controlled trial in childhood IgA nephropathy

Clin J Am Soc Nephrol. 2011 Jun;6(6):1301-7. doi: 10.2215/CJN.08630910. Epub 2011 Apr 14.

Abstract

Background and objectives: Children with IgA nephropathy showing diffuse (>80%) mesangial proliferation are at high risk for end-stage renal failure (ESRF). A previous controlled trial showed that combination therapy consisting of prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease reduces immunologic renal injury and prevents the progression of sclerosed glomeruli. The objective of this study was to evaluate the long-term effectiveness of combination therapy in children with IgA nephropathy showing diffuse mesangial proliferation.

Design, setting, participants, & measurements: A secondary analysis of a multicenter, randomized, controlled trial involving 78 children with IgA nephropathy who received either 2-year combination therapy or heparin-warfarin and dipyridamole (control) therapy was conducted.

Results: The median duration of observation was 10 years (range, 0.5 to 18). Two of 40 patients (5%) who received combination therapy and five of 34 patients (14.7%) who received control therapy developed ESRF. A Kaplan-Meier plot of renal survival showed that the outcomes of patients in the combined therapy group were better than those in the control therapy group (log-rank P = 0.03). The 10-year renal survival probability of each group was 97.1% (95% confidence interval, 81.4 to 99.6%) and 84.8% (95% confidence interval, 55.4 to 95.5%), respectively. The Cox proportional hazards model showed that the 2-year combination therapy was significantly associated with renal survival in both univariate and multivariate analyses.

Conclusions: Two-year combination therapy not only ameliorated the activity of the acute phase of nephritis but also improved the long-term outcome of severe childhood IgA nephropathy.

Publication types

  • Meta-Analysis
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Anticoagulants / therapeutic use*
  • Azathioprine / therapeutic use*
  • Cell Proliferation / drug effects
  • Child
  • Dipyridamole / therapeutic use*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Glomerulonephritis, IGA / complications
  • Glomerulonephritis, IGA / diagnosis
  • Glomerulonephritis, IGA / drug therapy*
  • Heparin / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Japan
  • Kaplan-Meier Estimate
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / prevention & control*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology
  • Male
  • Prednisolone / therapeutic use*
  • Proportional Hazards Models
  • Prospective Studies
  • Proteinuria / drug therapy
  • Proteinuria / etiology
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Immunosuppressive Agents
  • Warfarin
  • Dipyridamole
  • Heparin
  • Prednisolone
  • Azathioprine