NDT Advance Access originally published online on June 30, 2007
Nephrology Dialysis Transplantation 2007 22(11):3362-3363; doi:10.1093/ndt/gfm437
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A case of post-allogeneic haematopoietic stem cell transplantation membranous nephropathy
Correspondence and offprint requests to: Email: toshiro{at}belle.shiga-med.ac.jpSir,
We read with special interest the paper by Terrier et al. [1], regarding the occurrence of membranous nephropathy (MN) after allogeneic haematopoietic stem cell transplantation (HSCT). The authors described five patients who presented with membranous nephropathy, with history and active manifestations of chronic graft-vs-host disease (GVHD) at MN diagnosis, suggesting that chronic GVHD might contribute to the development of MN after allogeneic HSCT. We have, however, encountered a patient who showed nephrotic syndrome due to MN after allogeneic HSCT without any history or manifestations of GVHD.
A 38-year-old Japanese man with acute myeloid leukaemia (AML, M4 with eosinophilia) in second remission underwent an allogeneic HSCT from an HLA-identical donor. Total body irradiation and cyclophosphamide were used as conditioning therapy, a short-time methotrexate and cyclosporine (CsA) as GVHD prophylaxis. As he did not show any evidence of acute or chronic GVHD, CsA was tapered and withdrawn after 10 months. Several months later, hypoalbuminaemia developed, and marked proteinuria was found at 20 months after HSCT; he was thus referred to our department. On admission he presented with nephrotic syndrome, with daily protein excretion of 13.1 g, serum albumin of 2.4 g/dl and reduced renal function (serum creatinine, 0.79 mg/dl and glomerular filtration rate, 44.5 ml/min). He had never presented any clinical or laboratory manifestations of chronic GVHD (e.g. skin lesions, gastrointestinal manifestations or liver function abnormalities), nor signs of recurrence of leukaemia. Serological studies including complements, anti-nuclear antibodies and hepatitis B/C, yielded negative/normal results. A percutaneous renal biopsy revealed normocellular glomeruli with mild capillary wall thickening and marked renal tubular atrophy with interstitial fibrosis. Immunofluorescent study revealed granular immune deposition for IgG on the capillary wall, but no deposition of IgA, IgM, C3 C4 or C1q. Electron microscopy showed small and discreet electron-dense subepithelial deposits without basement membrane reaction, indicating early stage MN. As we suspected, his renal interstitial lesions might be evoked by CsA nephrotoxicity, we initiated corticosteroid therapy (prednisolone, 40 mg/day).
As described by Terrier et al. [1], several reviews of the literature reveal a close temporal relationship between the development of MN shortly after cessation of immunosuppressants and the diagnosis/presentation of chronic GVHD in allogeneic HSCT patients [1–5]. Further, there are few reports describing MN patients without acute or chronic GVHD after allogeneic HSCT, indicating that MN is thought to be a renal manifestation of GVHD. As his nephrotic syndrome developed after the cessation of CsA, MN is thought to be the only manifestation of chronic GVHD. Our patient is, however, characterized by the presentation of MN without any history or manifestations of GVHD; thus, there is a possibility that de novo MN might have occurred in our case. Our case merits presentation because further accumulation of clinical studies including case reports is necessary, to confirm whether MN is a real manifestation of GVHD after allogeneic HSCT or merely a coincidence.
Conflict of interest statement. None declared.
Department of Internal Medicine
Shiga University of Medical Science
Otsu, Shiga, 520-2192, Japan
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] - Brukamp K, Doyle AM, Bloom RD, Bunin N, Tomaszewski JE, Cizman B. 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] - Reddy P, Johnson K, Uberti JP, et al. Nephrotic syndrome associated with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transpl (2006) 38:351–357.[CrossRef][Web of Science][Medline]
- Nakashima H. Membranous nephropathy is developed under Th2 environment in chronic graft-versus-host disease. Med Hypotheses (2007) doi:10.1016/j.mehy.2007.02.015 [Epub ahead of print].
- Otani M, Shimojo H, Shiozawa S, Shigematsu H. Renal involvement in bone marrow transplantation. Nephrology (2005) 10:530–536.[CrossRef][Medline]
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