Does rituximab treat recurrent focal segmental glomerulosclerosis post-renal transplantation?

Abstract

Sirs, B cell depletion with rituximab, a chimeric monoclonal IgG1-kappa antibody that binds specifically to the CD20 antigen, has been shown to reduce pre-B and B lymphocytes in vivo and has become an effective treatment for adults and children with lymphomas and post-transplant lymphoproliferative disorders (PTLD), rheumatoid arthritis and other autoimmune diseases, including systemic lupus erythematosus [1–7]. However, we read with great interest the recent case report published in your journal by Nozu et al., in which rituximab treatment for PTLD induced complete remission of nephrotic syndrome due to the recurrence of focal segmental glomerulosclerosis (FSGS) in a 12-year-old boy six months post-renal transplantation [8]. Interestingly, another similar case report has been reported in the literature recently of a seven-year-old boy who had immediate FSGS recurrence and who developed EpsteinBarr virus-driven diffuse large cell lymphoma five months post-transplantation, which was successfully treated with rituximab, with the resolution of proteinuria at follow-up of seven months [9]. We present two children with recurrent FSGS post-renal transplantation who failed to respond to conventional therapies using the intensive protocol of plasmapheresis, corticosteroid pulses and cyclophosphamide over a twomonth period by Cochat et al. [10]. As they developed primary cytomegalovirus (CMV) infection with this intensive immunosuppressive regimen and continued to have nephrotic syndrome, we initiated treatment with intravenous rituximab, due to its favourable side-effect profile with less infectious complications. However, we felt it important to inform your readers that our patients without PTLD failed to respond to rituximab therapy, unlike the published case reports [8, 9]. The first case is a 6-year-old boy who has been followed up for eight months post-renal transplant. His mother is a 32-year-old lady who has had biopsy-proven minimal change nephrotic syndrome for 5 years, which has been responsive to tacrolimus therapy and is now proteinuricfree with a plasma creatinine of 55 μmol/l. We have been unable as of yet to find a genetic cause of possible familial FSGS in this family, as no mutation in podocin or WT1 has been identified. Her son presented with steroid-resistant nephrotic syndrome (SRNS) at the age of 2 years, who also failed to respond to cyclophosphamide and ciclosporin therapies. He required regular 20% albumin infusions and underwent laparoscopic bilateral native nephrectomies when he was 2.7 years old after gastrostomy and then peritoneal dialysis (PD) catheter insertions. He was stabilised on PD and underwent a deceased donor renal transplant, aged 5.5 years for end-stage renal failure (ESRF), secondary to biopsy-proven FSGS. The donor was a 17-year-old CMV-positive man who died from a subarachnoid haemorrhage (with recipient EBV and CMVnaive). The mismatch was 0,1,1 with a cold ischaemia time of 14 h. Our patient developed early recurrence of FSGS without acute tubular necrosis, with significant albuminuria (urine albumin:creatinine ratios of 700–1,146 mg/mmol) Pediatr Nephrol (2007) 22:158–160 DOI 10.1007/s00467-006-0260-x