NDT Advance Access originally published online on April 2, 2008
Nephrology Dialysis Transplantation 2008 23(8):2700-2701; doi:10.1093/ndt/gfn110
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Rituximab in membranous nephropathy after haematopoietic stem cell transplantation
E-mail: m.ferrannini{at}inwind.it
Sir,
Recently we read with interest the paper of Terrier et al [1] and the letter of Sugimoto et al [2] regarding the occurrence of membranous nephropathy (MN) after haematopoietic stem cell transplantation (HSCT). Terrier used Rituximab, a monoclonal CD20 antibody, in 1 out of 5 patients without important benefit; Sugimoto used corticosteroid therapy with success. Looking at the data, a large body of evidence suggests a role of activated B lymphocytes in the pathogenesis of idiopathic MN; therefore, it is considered an immunomediated glomerulonephritis [3]. In MN post-HSCT renal damage could be due to conditioning therapy, nephrotoxic therapies to prevent GVHD and their natural withdrawal in the follow-up with a decrease in immunosuppression [4]. Hence, direct nephrotoxic effects as well as direct or indirect humoral activation could be invoked as pathogenetic mechanisms [1].
We report a case of nephrotic syndrome (NS), without cGVHD manifestation, due to MN post-HSCT treated with Rituximab. A 68-year-old white woman with follicular Non-Hodgkin's Lymphoma (NHL, stage III) underwent an allogenic HSCT from an HLA-identical donor. A conditioning regimen consisting of steroids and cyclosporine (CsA) was stopped early due to worsening of renal function and hypertensive crisis with remission of treatment-related complications. Twenty-three months after transplantation and 10 months after the interruption of all immunosuppressive therapies, she presented with NS, with protein excretion of 35.2 g/24 h, serum albumin level 2.8 g/dl, moderate renal function impairment [creatinine 0.88 mg/dl, measured creatinine clearance –(CrCl) 28 ml/min, calculated CrCl 49.9 ml/min]. She had never presented any evidence of cGVHD nor NHL recurrence. A renal biopsy found subepithelial deposits in electron microscopy, and IgG and C3 in granular deposits by immunofluorescence indicating early stage MN. At first, she was treated only with corticosteroid therapy (methylprednisolone 1 g/day for 3 days; then prednisone decreased until 0.5 mg/kg/day), proteinuria relapsed after the first month. Patient was not eligible for combining corticosteroids and CsA therapies due to previous nephrotoxicity, and other myelosuppressive therapies were avoided. Then therapy was changed to Rituximab, 375 mg/m2 weekly for four doses. The results were a sustained complete remission of proteinuria (7 months at the last follow-up), serum albumin and renal function normalization and the absence of adverse effects. In our case the onset of MN seems to be temporarily associated with the suspension of immunosuppressive therapy but patients did not manifest any evidence of cGVHD. As well as other few reports described, MN after HSCT without GVHD is thought to be a renal manifestation of GVHD. Thus we cannot exclude both a de novo MN occurred after HSCT and a secondary form in which MN may be the unknown form of renal cGVHD. Our case merits presentation because of the encouraging results we had with Rituximab. There are few reports describing rituximab use in MN post-HSCT with discordant results. According to immunomediated MN theory, also in the secondary form, an agent that specifically interferes with B cells would ideally represent the first step towards selective therapy.
Conflict of interest statement. None declared.
1 Department of Medicine Nephrology and Dialysis Unit 2 Department of Internal Medicine, "Tor Vergata" University, Rome, Italy
Notes
Editorial Note: Dr Terrier et al declined the invitation to reply to this letter.
References
- Terrier B, Delmas Y, Hummel A, et al. Post-allogeneic haematopoietic stem cell transplantation membranous nephropathy: clinical presentation, outcome and pathogenic aspects. Nephrol Dial Transplant (2007) 22:1369–1376.
[Abstract/Free Full Text] - Sugimoto T, Tanaka Y, Sakaguchi M, et al. A case of post-allogeneic haematopoietic stem cell transplantation membranous nephropathy. Nephrol Dial Transplant (2007) 22:3362–3363.
[Free Full Text] - Remuzzi G, Chiurchiu C, Abbate M, et al. Rituximab for idiopathic membranous nephropathy. Lancet (2002) 360:923–924.[CrossRef][Web of Science][Medline]
- Brukamp K, Doyle AM, Bloom RD, et al. Nephrotic syndrome after hematopoietic cell transplantation: Do glomerular lesions represent renal graft-versus-host disease? Clin J Am Soc Nephrol (2006) 1:685–694.
[Abstract/Free Full Text]
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