Rituximab treatment of collapsing C1q glomerulopathy: clinical and histopathological evolution

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/m 2 ) 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.

Successful treatment of C1q nephropathy with CD19 targeted Rituximab therapy

“…Sinha et al reported a case of steroid dependent C1qN in an 11 year old boy who was treated successfully with rituximab (375 mg/m 2 weekly for 4 weeks) . The mechanism of beneficial effect of this agent remains unclear but could be related to inhibition of production of pathological immunoglobulins that bind C1q or binding to B cells in tubulointerstial/ mesangial infiltrates . This case also suggests the promise in titrating rituximab to CD‐19 levels rather than going by fixed dosage schedules …”

Resolution of clinical and pathologic features of C1q nephropathy after rituximab therapy

“…While there are no reports of the successful use of rituximab in the management of C1qN, it is conceivable that B-cell depletion may reduce pathogenic C1q activation by decreasing antibody and new immune complex formation [7]. Here, we report two patients with symptomatic C1qN where dramatic improvement in clinical symptoms and biochemical parameters were seen following rituximab therapy.…”

“…The decision to use rituximab in our patients was taken after conventional options were exhausted. To our knowledge rituximab treatment for C1qN has been reported only once [7]. A 13-year-old girl showed initial improvement following treatment with rituximab; however, repeat administration 20 months later failed to impact the disease course, possibly due to marked chronic glomerular damage that was not reversible with B-cell depletion.…”

Current status and issues of C1q nephropathy

“…Since the first report of C1q nephropathy by Jennette and Hipp, various case reports have also appeared [20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Among the cases included are rare cases featuring unusual clinical course, atypical pathological findings, involvement of genetic diseases and viral infection.…”