NDT Advance Access originally published online on November 2, 2007
Nephrology Dialysis Transplantation 2008 23(1):425; doi:10.1093/ndt/gfm616
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Post-transplant focal segmental glomerulosclerosis refractory to plasmapheresis and rituximab therapy
Email: gknoll{at}ottawahospital.on.caSir,
Primary focal segmental glomerulosclerosis (FSGS) recurs in 20 to 50% of kidney transplants [1]. Recently, there have been reports demonstrating the successful use of rituximab for recurrent post-transplant FSGS [2–4]. We report a case of recurrent FSGS that was refractory to both plasmapheresis and rituximab therapy.
A 48-year-old female with biopsy-proven FSGS underwent living kidney transplantation. She received anti-thymocyte globulin, tacrolimus, mycophenolate mofetil and prednisone. Her immediate post-transplant course was uneventful and her serum creatinine was 1.0 mg/dl on day 2. Fifteen days post-transplant, she was oedema free, her proteinuria had fallen from 7.8 to 3.4 g/day and she was not on an ACE-inhibitor or angiotensin receptor blocker. One month post-transplant, she had oedema, a weight gain of 4.7 kg, a creatinine of 1.3 mg/dl and her proteinuria had increased to 5.56 g/day.
A transplant biopsy was performed, which showed no evidence of tubulitis or segmental sclerosis (corticomedullary junction not sampled). Immunofluorescence showed 1+ IgM staining in the mesangium and C4d was negative. Electron microscopy showed diffuse effacement of the foot processes and there were no electron dense deposits. The pathological findings were consistent with recurrent FSGS [1]. Plasmapheresis was started and she received 13 exchanges over 4 weeks. There was no response; a second renal biopsy was thus performed, which showed ongoing evidence of FSGS. Plasmapheresis was restarted and she received another 13 exchanges over 4 weeks. After the final exchange, she had 6.41 g/day of proteinuria. Due to the lack of response, she was given six doses of rituximab (600 mg or 375 mg/m2 per dose) over 8 weeks. Unfortunately, there was no response and she had 5.42 g/day of proteinuria.
Rituximab, a monoclonal antibody directed against CD20, has been reported by several investigators to successfully treat post-transplantation FSGS [2–5]. The first two reports describing rituximab for recurrent FSGS were unique, in that they both occurred in the setting of post-transplant lymphoproliferative disorder [2,3], while the subsequent two cases were not [5]. It is not clear why our patient was resistant to rituximab therapy, given the reported experience in the literature to date. It is unlikely to be related to insufficient dose, as she received a total of 3600 mg of rituximab and her B cells were depleted with therapy (0.1% CD19 and 0.2% CD20 positive B cells 4 weeks post-rituximab).
In conclusion, we have shown that rituximab, given in an adequate dose, does not always lead to a remission in recurrent FSGS. These findings suggest that clinical equipoise exists regarding the use of rituximab for post-transplant FSGS and that randomized trials are needed to properly address this issue.
(See related article by M. S. Ahmed and C. F. Wong. Rituximab and nephrotic syndrome: a new therapeutic hope? Nephrol Dial Transplant 2008; 23: 11–17.)
1Division of Nephrology
Kidney Research Center
Ottawa Health Research Institute
2Department of Pharmacy
The Ottawa Hospital
3The Clinical Epidemiology Program
Ottawa Health Research Institute
Ottawa, Ontario, Canada
References
- Vincenti F, Ghiggeri G. New insights into the pathogenesis and the therapy of recurrent focal glomerulosclerosis. Am J Transplant (2005) 5:1179–1185.[CrossRef][Web of Science][Medline]
- Pescovitz MD, Book BK, Sidner RA. Resolution of recurrent focal segmental glomerulosclerosis proteinuria after rituximab treatment. N Engl J Med (2006) 354:1961–1963.
[Free Full Text] - Nozu K, Iijima K, Fujisawa M, Nakagawa A, Yoshikawa N, Matsuo M. Rituximab treatment for posttransplant lymphoproliferative disorder (PTLD) induces complete remission of recurrent nephrotic syndrome. Pediatr Nephrol (2005) 20:1660–1663.[CrossRef][Web of Science][Medline]
- Gossman J, Scheuermann EH, Porubsky S, Kachel HG, Geiger H, Hauser I. Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant patient with relapsed focal segmental glomerulosclerosis. Transplant Int (2007) 20:558–562.[CrossRef][Web of Science][Medline]
- Hristea D, Hadaya K, Marangon N, et al. Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab. Transplant Int (2007) 20:102–105.[CrossRef][Web of Science][Medline]
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Related articles in NDT:
- Rituximab and nephrotic syndrome: a new therapeutic hope?
- Muhammad Shahed Ahmed and Christopher F. Wong
NDT 2008 23: 11-17.[Extract] [FREE Full Text]
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