Rituximab treatment of collapsing C1q glomerulopathy: clinical and histopathological evolution.
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.
Bitzan
Martin
M
Department of Pediatrics, Montreal Children's Hospital/McGill University, Montreal, QC, Canada. martin.bitzan@muhc.mcgill.ca
Ouahed
Jodie D
JD
Krishnamoorthy
Preetha
P
Bernard
Chantal
C
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D001706:Biopsy; D016516:CD4-CD8 Ratio; D015922:Complement C1q / Q000276:immunology* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab; D016559:Tacrolimus / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D005938:Glucocorticoids; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab; D015922:Complement C1q; D011241:Prednisone; D016559:Tacrolimus