Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report two cases of nephrotic syndrome presenting 18 and 20 months after allogeneic stem cell transplantation (alloSCT) with chronic myelogenous leukemia. Both patients had acute and chronic graft-versus-host disease (GVHD) and renal biopsy findings of membranous glomerulopathy (MG). A review of the literature revealed 10 additional cases of immune-complex-mediated glomerular disease following alloSCT, 8 of which were diagnostic of MG. All patients showed evidence of acute or chronic GVHD. Patients typically presented with preserved renal function (mean creatinine 1.2 mg/dl) and full nephrotic syndrome including heavy proteinuria (mean 9.2 g/24 h), edema, hypoalbuminemia (mean 2.1 g/dl) and hypercholesterolemia (mean 472 mg/dl). Most patients showed stabilization of renal function and significant decreases in proteinuria when treated with steroids and/or cyclosporine. The close temporal association as well as evidence from murine models of GVHD support a pathogenetic association between GVHD and the development of MG.
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PMID:Membranous glomerulopathy associated with graft-versus-host disease following allogeneic stem cell transplantation. Report of 2 cases and review of the literature. 1168 93

Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by intraglomerular lipoprotein thrombi associated with severe proteinuria and frequent progression to renal failure. The histologic hallmark of LPG is the presence of laminated thrombi, consisting of lipid droplet, within the lumina of dilated glomerular capillaries. The findings of thrombi consisting of lipoproteins raised the possibilities that LPG might be related to a primary abnormality in lipid metabolism. However, the precise pathogenic basis of LPG remains unresolved. It was herein found that chronic graft-versus-host disease (GVHD) induced by the transfer of Ia-incompatible spleen cells from B6.C-H2(bm12) into coisogenic C57BL/6 mice with deficiency of Fc receptor gamma chain (FcRgamma) resulted in glomerulopathy that resembled LPG. The uptake of acetylated LDL was partially decreased in peritoneal macrophages isolated from FcRgamma-deficient mice compared with wild-type mice, suggesting that partial impairment of modified LDL uptake might contribute to the development of LPG associated with chronic GVHD in FcRgamma-deficient mice. LPG has been suggested to be a disorder of primary abnormality in lipid metabolism; these findings would therefore provide novel insight into the disease process.
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PMID:Chronic graft-versus-host autoimmune disease in Fc receptor gamma chain-deficient mice results in lipoprotein glomerulopathy. 1203 82

Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT), but membranous glomerulopathy (MG) has rarely been described as a manifestation of chronic GVHD. We report two cases of MG in children who underwent allogeneic HSCT. The clinical findings were characterized by edema of the lower extremities and nephrotic proteinuria in one case and hypertension, hematuria and edema with non-nephrotic proteinuria in the other one. Renal biopsy was consistent with MG and appropriate immunosuppressive therapy was prescribed. Both patients achieved complete remission and are alive without renal disease 4 and 2 years after the diagnosis of MG. The normal levels of albumin and non-nephrotic proteinuria in one of the two cases raise the question of whether the real incidence of MG after HSCT is underestimated. Therefore, we strongly suggest regular urine analysis during the follow-up of children undergoing HSCT in order to diagnose MG early.
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PMID:Membranous glomerulopathy in children given allogeneic hematopoietic stem cell transplantation. 1626 22

Lipoprotein glomerulopathy (LPG) is a unique entity of renal lipidosis characterized by peculiar histopathologic characteristics of lipoprotein thrombi and an abnormal plasma lipoprotein profile resembling type III hyperlipoproteinemia, with a marked increase in serum apolipoprotein E (apoE) concentrations. At present, 65 cases have been reported worldwide, although most patients are found in Japan and east Asian countries. Recently, we identified 4 types of novel apoE mutations associated with LPG. In particular, a mutation designated apoE Sendai, in which arginine 145 is substituted with proline, occurs in the majority of Japanese patients. The virus-mediated transduction of apoE Sendai resulting in the development of LPG in apoE-deficient mice confirms the etiologic role of apoE mutation in LPG. Conversely, experimental graft-versus-host disease induced in Fc receptor gamma-chain-deficient mice showed LPG-like lesions in glomeruli without apoE mutations. Considered together, we believe that intrinsic factors in the kidney also contribute to the induction of LPG. Today, apoE and related lipid abnormalities are reported to have an important role in the development of various renal diseases, eg, diabetic nephropathy and immunoglobulin A nephropathy. In this article, we review clinical and histopathologic features of LPG, describe the etiologic role of apoE variants and intrinsic renal factors, and discuss the impact of LPG on mechanisms of other renal diseases.
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PMID:Impact of lipoprotein glomerulopathy on the relationship between lipids and renal diseases. 1643 Dec 49

Systemic sclerosis (SSc) characteristically consists of fibrotic changes in various organs, and immunological abnormality is the main cause of the disease. Although high-dose immunosuppressive therapies with autologous or allogeneic hematopoietic stem cell support can reverse the disease course, they have a high treatment-related mortality. We report the successful use of nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for SSc. A 40-year-old woman with diffuse scleroderma and interstitial pneumonia underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical sibling after conditioning with low-dose total-body irradiation and fludarabine. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and mycophenolate mofetil. No infection or acute GVHD developed. One year after transplantation, the patient developed membranous glomerulopathy caused by chronic GVHD that was successfully treated with prednisolone. The patient's skin score decreased dramatically, and her pulmonary function is stable 4 years after transplantation. Nonmyeloablative allogeneic HSCT may be more effective than conventional therapies for SSc.
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PMID:Long-term follow-up after nonmyeloablative allogeneic hematopoietic stem cell transplantation for systemic sclerosis. 1848 58

The nephrotic syndrome is a rare complication of allogeneic stem cell transplantation (alloHSCT). We present two cases of nephrotic syndrome during chronic graft-versus-host disease (GvHD) involving altered cytokine gene expression in renal tissue. A patient with acute lymphatic leukemia demonstrated nephrotic syndrome due to minimal change disease as a marker of chronic GvHD. A patient with acute lymphoblastic leukemia suffered from severe nephrotic syndrome due to membranous glomerulopathy. In the two presented cases of GvHD-linked nephrotic syndrome, increased cytokine gene expression [tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interferon gamma (IFN-gamma), interleukin 2 (IL-2), IL-6, and IL-10] assessed using semiquantitative evaluation with reverse transcriptase polymerase chain reaction (RT-PCR) in situ on renal biopsy was observed.
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PMID:Glomerular lesion and increased cytokine gene expression in renal tissue in patients with decompensated nephrotic syndrome due to chronic GvHD. 2044 93

Even in the era of pharmacological calcineurin inhibitors, a current major challenge in organ transplantation remains the development of immunosuppressive regimens that protect against rejection. One potentially effective procedure is the use of donor-specific anergic T cells generated ex vivo and adoptively transferred back into the recipient after transplantation. In our own work, we first investigated the effect of anergic cells on the prolongation of graft survival in non-human primates. In six animals, half of the recipients survived for over one yr (all animals died or were killed within eight yr). The cause of death was acute renal failure because of cellular rejection (one), uncontrolled bleeding after renal biopsy (two), hydronephrosis probably because of ureteral stenosis (one), and chronic rejection (one). The remaining animal was killed at the end of the study. No infection, malignancy, or signs of graft versus host disease (GVHD) was observed in any of these monkeys. Except for the one animal that died of acute cellular rejection, there was no evidence of tubular infiltration by mononuclear cells, glomerular damage, or parenchymal necrosis. In all animals surviving for more than one yr, a mild grade of interstitial fibrosis, an increase in mesangial matrix, or glomerulopathy was noted. In two of three monkeys, no vascular narrowing of the luminal area caused by fibrointimal thickening of arteries was noted, and arteriosclerotic change was dominant. In this chapter, we summarize the efficacy and limitations of our strategy.
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PMID:Prolongation of renal allograft survival by anergic cells: advantages and limitations. 2059 Jun 86

Glomerulopathy is an uncommon but increasingly recognized complication of hematopoietic cell transplantation. It typically manifests as membranous nephropathy, less commonly as minimal change disease, and rarely as proliferative glomerulonephritis. There is evidence to suggest that these glomerulopathies might represent manifestations of chronic graft-versus-host disease. In this report, we focus on membranous nephropathy as the most common form of glomerulopathy after hematopoietic cell transplantation. We present a case of membranous nephropathy that developed 483 days post-allogeneic hematopoietic stem cell transplantation in a patient with a history of acute graft-versus-host disease. We also share our experience with 4 other cases of membranous nephropathy occurring after allogeneic hematopoietic stem cell transplantation. Clinicopathologic correlates, including the association with graft-versus-host-disease, HLA antigen typing, glomerular deposition of immunoglobulin G (IgG) subclasses, subepithelial colocalization of IgG deposits with phospholipase A2 receptor staining, C4d deposition along the peritubular capillaries, and treatment, are discussed with references to the literature.
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PMID:Membranous nephropathy as a manifestation of graft-versus-host disease: association with HLA antigen typing, phospholipase A2 receptor, and C4d. 2530 85

Renal injury in hematopoietic cell transplant recipients may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease, and can involve glomerular, tubulointerstitial, and vascular structures. We reviewed renal pathology from 67 patients at a single institution (2009-2014), including 14 patients with biopsy for clinical dysfunction, 6 patients with surgical kidney resection for other causes, and 47 autopsy patients. Kidney specimens frequently contained multiple histopathologic abnormalities. Thrombotic microangiopathy, membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis were the most common glomerular findings. Pathologies not previously reported in the hematopoietic cell transplant setting included collapsing glomerulopathy, antiglomerular basement membrane disease, fibrillary glomerulonephritis, and in the case of two surgical resections distinctive cellular segmental glomerular lesions that defied classification. Kidney specimens frequently demonstrated acute tubular injury, interstitial fibrosis, arteriolar hyaline, and arteriosclerosis. Other kidney findings at autopsy included leukemia and amyloid (both recurrent), diabetic nephropathy, bacterial infection, fungal invasion, and silver deposition along glomerular and tubular basement membranes. Also in the autopsy cohort, C4d immunohistochemistry demonstrated unexpected membranous nephropathy in two patients, yet C4d also colocalized with arteriolar hyaline. This retrospective hematopoietic cell transplant cohort illustrates multifaceted renal injury in patients with renal dysfunction, as well as in patients without clinically recognized kidney injury.
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PMID:Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series. 2701 34