Pediatric Nephrology

, Volume 23, Issue 8, pp 1355–1361 | Cite as

Rituximab treatment of collapsing C1q glomerulopathy: clinical and histopathological evolution

  • Martin Bitzan
  • Jodie D. Ouahed
  • Preetha Krishnamoorthy
  • Chantal Bernard
Brief Report

Abstract

A 13-year-old girl with obesity and hyperinsulinism developed steroid-resistant nephrotic syndrome due to collapsing glomerulopathy with dominant C1q-containing mesangial immune deposits (CG/C1qN). She became overtly diabetic while receiving alternate-day prednisone and tacrolimus, requiring insulin injections. Despite the addition of mycophenolate mofetil to the treatment regimen, renal function subsequently declined. Rituximab (four weekly doses of 375 mg/m2) was tried 6 months after initial presentation and 3 months after weaning all glucocorticoids. Glomerular filtration rate (GFR) and proteinuria improved. Unexpectedly, blood sugar control normalized 6 weeks after antibody infusion. Rituximab was readministered 20 months after the first course because of deteriorating renal function, but the effect on GFR and proteinuria was modest. A retrospective analysis revealed that tubulointerstitial infiltrates present in the biopsies prior to treatment with rituximab contained numerous CD20+ and CD3+ (CD4 > CD8) lymphocyte aggregates. Rebiopsy 10 weeks after repeat rituximab therapy demonstrated the elimination of B-cell infiltrates and the apparent decrease of interstitial T-cell infiltrates, yet persistent, advanced global glomerulosclerosis, interstitial fibrosis and tubular atrophy. In conclusion, CG/C1qN was associated with B- and T-cell-rich tubulointerstitial infiltrates. B-cell-directed therapy delayed clinical progression during early disease but failed to prevent or ameliorate chronic changes, despite effective tissue B-cell clearance. The incidental resolution of diabetes was noted after rituximab treatment.

Keywords

C1q nephropathy Diabetes Focal segmental glomerulosclerosis Immunosuppression Lymphocyte infiltrate Nephrotic syndrome Tacrolimus 

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Copyright information

© IPNA 2008

Authors and Affiliations

  • Martin Bitzan
    • 1
    • 2
  • Jodie D. Ouahed
    • 1
  • Preetha Krishnamoorthy
    • 1
  • Chantal Bernard
    • 1
  1. 1.Department of PediatricsMontreal Children’s Hospital/McGill UniversityMontrealCanada
  2. 2.Division of Nephrology, Department of PediatricsMontreal Children’s HospitalMontrealCanada

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