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Treatment of severe IgA nephropathy in children
1Department of Pediatrics, Indiana University School of Medicine, Indianapolis.
Insights
Prednisone and azathioprine treatment significantly reduced proteinuria and disease activity in children with severe IgA nephropathy (IgAN). While chronicity scores remained stable, this combination therapy shows promise for managing IgAN in pediatric patients.
Area of Science:
- Pediatric Nephrology
- Immunology
- Pharmacology
Background:
- Severe IgA nephropathy (IgAN) in children presents with significant proteinuria, hypertension, and renal insufficiency.
- Histological findings in severe IgAN include segmental sclerosis, crescent formation, and IgA deposition.
- Limited data exists on the efficacy of immunosuppressive therapy in pediatric IgAN.
Purpose of the Study:
- To evaluate the efficacy of prednisone and azathioprine in treating severe IgA nephropathy in children.
- To assess the impact of this treatment on proteinuria, renal histology, and disease activity.
Main Methods:
- Ten children with severe IgAN received prednisone and azathioprine for one year.
- Kidney biopsies were performed before and after treatment, scored for activity and chronicity.
- Proteinuria levels and histological parameters were analyzed.
Main Results:
- Significant reduction in proteinuria (4052 to 1692 mg/day) and disease activity scores (4.35 to 2.28) after one year.
- Marked decrease in cellular crescents (21.2% to 0.94%) and less prominent GBM IgA deposition.
- Chronicity scores remained unchanged, indicating no significant progression of scarring during treatment.
Conclusions:
- Prednisone and azathioprine combination therapy appears beneficial in reducing proteinuria and active inflammation in pediatric IgAN.
- Long-term follow-up shows sustained stability in most patients, though some developed renal insufficiency due to scarring.
- A controlled clinical trial is warranted to confirm these findings and establish optimal treatment protocols.
Abstract:
We treated ten children with severe IgA nephropathy (IgAN) [proteinuria greater than 1 g/day, hypertension, renal insufficiency, segmental sclerosis, crescent formation and/or glomerular basement membrane (GBM) deposition of IgA] with prednisone and azathioprine for 1 year. Following the year of therapy, seven of the ten children underwent a repeat kidney biopsy. All biopsies were scored for activity (percentage of glomeruli demonstrating crescent formation, degree of mesangial proliferation and interstitial infiltrate; maximum score = 9) and chronicity (percentage of glomeruli demonstrating fibrous crescents, segmental sclerosis, global sclerosis, and degree of tubular atrophy and interstitial fibrosis; maximum score = 12). After 1 year of therapy, the protein excretion of all the children decreased significantly (P less than 0.01) from 4,052 +/- 3,190 mg/day to 1,692 +/- 1,634 mg/day. The activity score decreased significantly (P less than 0.01) from 4.35 +/- 0.94 prior to therapy to 2.28 +/- 0.75 after therapy while the chronicity score was unchanged (5.42 +/- 1.7 vs 5.85 +/- 2.0). The percentage of glomeruli demonstrating cellular crescents decreased (P less than 0.05) from 21.2 +/- 21.7% prior to therapy to 0.94 +/- 2.4% after therapy. Mesangial deposition of IgA persisted but GBM deposition of IgA was less prominent after therapy. During the follow-up period (mean 2.6 years, range 9 months-7.5 years), one child required brief retreatment for biopsy-confirmed recurrence of active disease, two children have developed renal insufficiency due to progressive scarring in the absence of inflammation, while the remaining seven are stable. We suggest that treatment with prednisone and azathioprine may be beneficial in children with severe IgAN and that a controlled clinical trial is warranted.