1 Departments of Nephrology,
2 Haematology and
3 Pathology, Ankara University School of Medicine, bn-i Sina Hospital, Ankara, Turkey
Correspondence and offprint requests to:
Gökhan Nergizoglu, ehit Cemalettin cad. 117/7, Aydinlikevler, 06130, Ankara, Turkey.
Keywords: graft-versus-host disease; nephrotic syndrome
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Introduction |
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Case |
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The patient had commenced hydroxyurea until alloHSCT was performed. Busulphan 4 mg/kg/day for 4 days and cyclophosphamide 60 mg/b.w./day for 2 days were administered as conditioning regimen. In December 1996, the patient received 10.4x108/b.w. mononuclear cells, 8.76x106/b.w. CD34+ cells, from her HLA-identic sibling. Cyclosporin A (CsA) was administered for GVHD prophylaxis from day -1 to day +180. Ten-months after alloHSCT, a mucosal ulceration and dryness in her mouth was observed. A mucosal form of cGVHD was diagnosed on the basis of clinical and biopsy findings. CsA (400 mg/day) and corticosteroid (16 mg/day) were commenced. Due to response in the lesions, the corticosteroid and CsA were gradually tapered.
In December 1997, the patient was admitted to the hospital because of bilateral ankle oedema and watery diarrhoea. On the physical examination, blood pressure was 110/70 mmHg, pulse was 78/min, and temperature was 36.7°C. Conventional cytogenetics revealed absence of Ph+ chromosome in 20 metaphases which was confirmed by Variable Non-Tandom Repeats as complete chimerism. She had partially healed mucositis in her mouth. In laboratory investigations; white cell count was 5400/mm3, haemoglobin level 13 g/l, platelet 178 000/mm3, sedimentation rate 99 mm/h. Urine test rendered (+++) proteinuria. Twenty-four hour urinary albumin loss was 9.9 g. Serum albumin was 2.8 g/dl, total protein 4.9 g/dl, blood creatinine 1.0 mg/dl, blood urea nitrogen 21 mg/dl, AST 11 U/l, ALT 14 U/l, ALP 82 U/l, GGT 35 U/l. Total cholesterol was 466 mg/dl and triglyceride 383 mg/dl. Antinuclear antibody was negative, anti double-stranded DNA was 1.9 IU/ml, serum immunoglobulin levels and complement levels (C3, C4) were within the normal range. Viral tests were; hepatitis B surface antigen (HBsAg) (-), anti HBsAg (+), cytomegalovirus IgM (-), IgG (+), EbsteinBarr virus IgM (-), IgG (+), hepatitis C virus antibody (-). Renal venous Doppler ultrasonography was normal excluding renal venous thrombosis. Abdominal ultrasonography chest X-rays were normal.
Renal biopsy was performed and membranous glomerulonephritis (MG) was diagnosed on the basis of light and immunofluorescence microscopy (Figure 1). There was mild thickening of the capillary basement membranes with mild interstitial fibrosis. No interstitial infiltration and any vascular abnormalities which may be the evidence for CsA toxicity were found. Immunofluorescence study showed the diffuse granular basement membrane deposition of IgG and absence of complement (C3) deposition.
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Discussion |
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Of the previous seven cases, two had minimal change disease [5] and five had MG [610]. Interestingly, an episode of acute GVHD, which was reported in all previous cases, was not detected in our patient. Immune complex-mediated renal injury plays a key role in the pathogenesis of MG. In experimental studies, lupus nephritis was induced extensively by murine GVHD models and it provides support that immune complex-mediated mechanism during the course of GVHD may have a role in the pathogenesis of MG [2]. Since T cells play a crucial role in initiating of GVHD, attempts at prevention and treatment of GVHD include immunosuppressive drugs such as CsA and methotrexate. Previous reported cases showed that CsA appears to have substantial efficacy in MG complicated with cGVHD. In the literature, two cases of cGVHD developed nephrotic syndrome after withdrawal of CsA treatment and the proteinuria decreased gradually when CsA was recommenced [6,7]. However, in the other case of cGVHD, nephrotic syndrome developed under the CsA treatment and there was MG along with CsA toxicity on renal biopsy. The CsA was ceased and chlorambusil and prednisolone were introduced. After three cycles of the treatment, there was no prominent response. CsA was recommenced and proteinuria decreased substantially [8]. In our case, nephrotic syndrome appeared under the CsA treatment, and proteinuria decreased and serum albumin returned to the normal level with increasing doses of corticosteroid and previous doses of CsA. In addition Sato et al. received a good response with increasing doses of corticosteroid in their case of MG associated with cGVHD [9]. Thus, it can be inferred that the likelihood of response to the immunosuppressive treatment appears to be effective in MG complicated with cGVHD. After increasing corticosteroid and without changing the doses of CsA, proteinuria decreased and serum albumin returned to the normal level. The patient has now been stable for more than 12 months.
In summary, glomerular disease can be a new cGVHD related immune disorder in bone marrow transplant recipients and more studies are needed to better clarify such an association.
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References |
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