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| Year : 2014 | Volume
: 25
| Issue : 5 | Page : 1062-1064 |
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| Chronic graft versus host disease and nephrotic syndrome |
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Samia Barbouch1, Hanene Gaied1, Khaoula Ben Abdelghani1, Rim Goucha1, Amel Lakhal2, Lamia Torjemen2, Fethi Ben Hamida1, Ezzedine Abderrahim1, Hedi Ben Maiz1, HafedhHedri1, Khedher Adel1
1 Department of Nephrology and Laboratory of Renal Pathology, LR00S001, Hôpital Charles Nicolle, Tunis, Tunisia
2 Department of Bone Transplantation, Tunis, Tunisia
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| Date of Web Publication | 2-Sep-2014 |
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 Abstract | | |
Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD). We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT). Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed membranous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.
How to cite this article:
Barbouch S, Gaied H, Abdelghani KB, Goucha R, Lakhal A, Torjemen L, Hamida FB, Abderrahim E, Maiz HB, HafedhHedri, Adel K. Chronic graft versus host disease and nephrotic syndrome. Saudi J Kidney Dis Transpl 2014;25:1062-4 |
How to cite this URL:
Barbouch S, Gaied H, Abdelghani KB, Goucha R, Lakhal A, Torjemen L, Hamida FB, Abderrahim E, Maiz HB, HafedhHedri, Adel K. Chronic graft versus host disease and nephrotic syndrome. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2023 Feb 9];25:1062-4. Available from: https://www.sjkdt.org/text.asp?2014/25/5/1062/139941 |
| Introduction | |  |
Graft versus host disease (GVHD) is a serious immunological complication of bone marrow transplantation (BMT) that results in significant morbidity and mortality. [1] It appears 100 days after transplantation, [2] and occurs when donor T lymphocytes react with foreign host cells. The pathophysiology is a complex process marked with host tissue damage caused by conditioning regimens, cytokines and cellular effectors through an immune response that includes donor T lymphocytes, antigen presenting cells and mechanisms of apoptosis. [3],[4],[5] Chronic kidney disease occurs in 20- 60% of BMT patients, and has been associated with the use of radiation and/or chemothera-peutic agents, GVHD and acute renal failure. [1]
Herein, we describe a patient who developed a late-onset nephropathy after BMT that was probably caused by GVHD.
| Case Report | | |
A 19-year-old woman with chronic myelogenous leukemia underwent a BMT from her sister with identical HLA in September 2008. At that time, she received cytarabine/cyclo-phosphamide as a conditioner plus cyclos-porine as the GVHD prophylaxis.
In November 2008, she developed thrombotic microangiopathy; therefore, cyclosporine treatment was stopped and replaced with mycophenolate mofetil.
About six months later, she developed skin eruption, lichen of the soft palate, cytolytic and cholestatic hepatitis. The diagnosis of chronic graft versus host disease (cGVHD) was made. The eruption improved with steroid therapy, which was gradually tapered and stopped in December 2010.
In January 2011, the patient developed edema; her blood pressure was 110/60 mm Hg, urina-lysis showed proteinuria +++; hematuria +++, laboratory investigations revealed, WBC 5400, Hb: 12 g/dL, platelets: 140,000, proteinuria up to 10 g/day, serum proteins: 40 g/L, serum albumin: 17 g/L, gamma globulin: 2.8 g/L, creatinine: 36 μmol/L, cholesterol: 11.79 mmol/ L, triglyceride: 4.23 mmol/L, aspartate trans-aminase (AST): 17 U/L, alanine transaminase (ALT): 10 U/L, anti-nuclear antibodies: negative and cryoglobulinemia: negative.
Her renal biopsy showed a specimen of renal cortical and medullar tissue that contained 35 glomeruli with two hyalinized glomeruli. The matrix expansion presented a mesangial hyper-cellularity. The glomerular basement membrane (GBM) was irregularly thinned with characteristic spikes. Granular deposition of IgG was seen with immunofluorescence.
The proteinuria decreased to 2.63 g/L after 45 days of corticosteroid treatment dosed at 1 mg/kg/d.
| Discussion | | |
Our patient developed GVHD eight months after BMT. The main risk factor for cGVHD is HLA mismatch; [3] our patient had no HLA mismatch. Its incidence is also higher in older recipients, [4] gender mismatch (female donor to male recipient) [4] and allogeneic BMT.
The role of B cells in cGVHD is not well established. Several studies found 35 different antibodies to be more prevalent in cGVHD, but none of the studies have convincingly demonstrated that these antibodies contribute to the clinical manifestations of tissue injury in cGVHD. In addition, tissue injury via immune complexes or vasculitis are not prominent features of cGVHD. [6] Several studies have suggested a possible collaboration between B and T cells in the pathogenesis of cGVHD. This is in accordance with the fact that T-helper cells, via CD40 ligand expression, are necessary for immuno-globulin isotype switching. [6] Additionally, treatment with rituximab resulted in an incomplete response in a bullous pemphigoid-cGVHD patient. [7] But, when adding daclizumab, an anti-CD25 antibody, a complete clinical response in combination with a complete decrease in bullous pemphigoid titer was observed. [6]
The BMT-related nephropathies are rare and include acute renal failure (ARF), hemolytic uremic syndrome (HUS), nephrotic syndrome (NS) and chronic renal failure (CRF). These nephropathies can be divided into two groups according to the time of appearance: Early-onset and late-onset (before or 150 days after BMT, respectively). Drugs, especially cyclos-porine A (CsA), and infections are responsible for the early-onset nephropathy that manifests as ARF and HUS. Conversely, late-onset nephropathies mainly present as GVHD-rela-ted NS, CRF and irradiation-related nephro-pathy.
An association of glomerular disease with simultaneous GVHD was reported in 47% of the patients. [5] Membranous glomerulonephritis (MGN) is the most frequent glomerular manifestation of chronic GVHD. Other reported forms of glomerulonephritis include minimal change disease (MCD), membranoproliferative glomerulonephritis, focal segmental glomerulo-sclerosis (FSGS), anti-neutrphil cytoplasmic antibodies (ANCA)-associated glomeruloneph-ritis, proliferative glomerulonephritis, and IgA nephropathy
Proximity of onset of the MGN to the cessation of immunosuppression and concomitant GVHD suggest that the glomerular injury is immune mediated. The possible role of withdrawal of CsA administered as prophylaxis of GVHD should be considered, and after either its re-introduction or increased dosage, clinical improvement was achieved in many patients with MGN, as observed also in our patient.
The finding of FSGS has been reported in patients with interferon therapy and high dosage chemotherapy for chronic myeloid leukemia, which provides evidence that high-dosage chemotherapy alone may be sufficient to result in severe podocyte injury. [8]
The diversity of organ involvement, the chronic nature of the illness and the hematological and immunological dysfunction associated with the syndrome contribute to the difficulties in successfully treating cGVHD. Therapeutic options included mostly steroids and cyclos-porine. [9],[10] Similar to idiopathic MCD, almost all patients achieved complete remission, and response was generally reached after 8-10 weeks of treatment. [2] However, concerning membranous nephropathy, prognosis does not seem so favorable: Only 27% achieved com-plete and 62% achieved partial remission. [11] Intravenous immunoglobulin (IVIG) may be one of the choices when patients do not respond to multiple immunosuppressive interventions. In fact, IVIG, with its effects of anti-idiotypic regulation and inhibition of cytokines, can modulate or reduce the severity of acute GVHD. However, the role of IVIG therapy in the prevention and treatment of GVHD is still not well established. [12]
We conclude that our patient presented with MGN as a manifestation of GVHD. Immuno-suppression seems to play a major role in controlling the disease and prognosis is apparently favorable.
| References | | |
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| 11. | Atkinson K, Horowitz MM, Gale RP, et al. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood 1990;75:2459-64.
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| 12. | Wang HH, Yang AH, Yang LY, et al. Chronic graft-versus-host disease complicated by neph-rotic syndrome. J Chin Med Assoc 2011;74: 419-22.
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Correspondence Address:
Dr. Samia Barbouch
Department of Nephrology and Laboratory of Renal Pathology, LR00S001, Hôpital Charles Nicolle, Tunis
Tunisia
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1319-2442.139941
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| This article has been cited by | | 1 |
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