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

Acute and chronic renal dysfunction are common after hematopoietic stem cell transplantation (HSCT). Although the pathology of chronic HSCT nephropathy is well described, the histologic changes that accompany acute renal dysfunction after HSCT are less well known because renal biopsies are rarely undertaken in the peritransplantation period. Archival renal tissue from consecutive HSCT recipients who died and underwent autopsy at a single center during an 8-year period was studied. Abnormalities of renal pathology were described, and associations of histologic abnormalities with clinical events were systemically studied. Abnormalities of renal histology were common among the 26 patients in this study. The 3 most common histologic abnormalities were glomerular sclerosis (19/26; 73%), tubular epithelial atypia (19/26; 73%), and tubular calcification (18/26; 69%). Tubulitis (16/24; 67%) and interstitial fibrosis (16/26; 62%) were also frequently observed. Clinical veno-occlusive disease was not associated with histologic evidence of thrombotic microangiopathy in the kidney at autopsy. Also, clinical graft-versus-host disease was not associated with renal tubulitis. Unexpectedly, the proportion of patients with tubular atrophy (54%) or interstitial fibrosis (62%) was high, considering the young age of the patients at transplantation and their normal pretransplantation creatinine clearance. Well-recognized histologic abnormalities are common in the kidneys of patients who die after HSCT. Although we did not demonstrate associations of these histologic changes with clinical variables before death, larger studies with prospectively collected renal tissue are warranted.
 ...
PMID:Renal pathology at autopsy in patients who died after hematopoietic stem cell transplantation. 1465 51

Fibronectin (FN) is the main extracellular matrix component in glomerulosclerotic lesions. There are different FN isoforms that result from alternative splicing at the EDA and EDB regions of FN mRNA. Increased inclusion of EDA and EDB, which can be elicited by TGFbeta, may be conducive to the development of glomerulosclerosis (GS). TGFbeta and IL-4 have previously been shown to play a role in the development of GS. In this study, the mRNA splicing patterns for EDA+ and EDB+ fibronectin were investigated in vivo in various experimental sclerotic glomerulopathies, in vitro in rat mesangial cells (MC) that were stimulated by TGFbeta or transfected with IL-4, and in human kidney biopsies with GS from patients with various kidney diseases. Analysis of glomerular FN mRNA demonstrated inclusion of both ED regions in rats with anti-Thy1 nephritis or chronic serum sickness and in mice with anti-GBM glomerulonephritis. Inclusion of both the EDA and EDB regions was associated with glomerular TGFbeta expression. In contrast, in mice with Th2-mediated graft-versus-host disease, a model for lupus nephritis, the FN transcripts included neither the EDA nor the EDB region, and renal TGFbeta expression was absent. Compared to normal MCs in culture, MCs transfected with IL-4 produced lower amounts of FN and demonstrated less EDA inclusion, while MC that had been treated with TGFbeta showed increased production of FN and more EDA inclusion. Renal biopsies from patients with renal diseases, except those taken from patients with lupus nephritis, showed higher TGFbeta levels, higher FN levels, and more EDA inclusion than controls. TGFbeta may be a key player in the development of GS by inducing local FN production and alternative splicing of FN mRNA. In lupus glomerulonephritis, in which the involvement of TGFbeta in GS is less prominent, Th2 cytokines such as IL-4 probably account for increased intrarenal collagen synthesis and subsequent FN accumulation from the circulation. In conclusion, neither alternative FN splicing, nor a high transcription level of TGFbeta, appears to be a general prerequisite for the development of GS.
 ...
PMID:Alternatively spliced isoforms of fibronectin in immune-mediated glomerulosclerosis: the role of TGFbeta and IL-4. 1537 54

Graft-versus-host disease (GVHD) is one of the most frequent complications that occur after hematopoietic stem cell transplantation (HSCT). Recently, renal involvement, including membranous nephropathy, focal segmental glomerulosclerosis, and minimal change disease, has been described as a manifestation of chronic GVHD. This case report describes a patient who developed antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis after HSCT. Following preparation with chemotherapy, a 29-year-old man with chronic myeloid leukemia underwent allogenic peripheral blood stem cell (PBSC) transplantation, after which first acute and then chronic GVHD developed. Treatment with prednisone resulted in improvement in the patient's GVHD. After the termination of steroid therapy and about 10 months after PBSC transplantation, nephritic syndrome appeared and the patient's serum creatinine value increased to 1.7 mg/dL. Laboratory evaluation revealed perinuclear antineutrophilic cytoplasmic antibody (p-ANCA) in the serum. Histological examination of renal biopsy tissue showed focal segmental proliferative glomerulonephritis with glomerulosclerosis in 20% of available glomeruli, large cellular crescents in 6% of glomeruli, and no staining of immunoglobulins or complement along the capillary walls. Electron microscopy revealed no immune deposits. After treatment with prednisone 60 mg/d, diltiazem 120 mg/d, and enalapril 10 mg/d, the proteinuria gradually decreased, and p-ANCA was undetectable. These findings suggest that in this patient the ANCA-associated glomerulonephritis was associated with renal involvement that occurred during the course of chronic GVHD.
 ...
PMID:Antineutrophil cytoplasmic antibody-associated glomerulonephritis in chronic graft-versus-host disease after allogenic hematopoietic stem cell transplantation. 1621 51

Heavy proteinuria after bone marrow transplantation (BMT) is rare. Pathology shows membranous glomerulonephritis (MGN) in most cases. After BMT, focal segmental glomerulosclerosis (FSGS) after resolution of MGN has not been reported. We describe a 13-year-old boy who had matched unrelated donor allogeneic BMT for relapsed acute lymphoblastic leukemia, complicated by chronic graft-versus-host disease. Nephrotic syndrome developed 1 year after BMT and renal biopsy revealed MGN. Immunosuppressive therapy achieved good clinical remission, and treatment was stopped after 15 months. He developed significant proteinuria 55 months later. The second renal biopsy showed FSGS without changes of MGN. This distinctive disease evolution gives inspiring implications. Complete morphological resolution of graft-versus-host disease-associated MGN, achieved in our case, has not been previously documented. Recurrent significant proteinuria after BMT is not necessarily due to previous renal lesion, and a repeat renal biopsy is indicated. The pathogenesis of MGN and FSGS are different, and different mechanisms of glomerular injury can interplay in a single patient after BMT. This case helps to expand our knowledge of the temporal morphological spectrum of renal lesions associated with BMT.
 ...
PMID:Focal segmental glomerulosclerosis after membranous glomerulonephritis in remission: temporal diversity of glomerulopathy after bone marrow transplantation. 1702 Jul 80

We describe the case of a male patient who was diagnosed with acute monoblastic leukemia and received a peripheral stem cell transplantation (PSCT) with peripheral blood hematopoietic progenitors. Because he was in clinical remission with no evidence of chronic graft-versus-host disease (GVHD), immunosuppression was withdrawn, and he developed nephrotic syndrome (NS) months later. A kidney biopsy showed focal segmental glomerulosclerosis (FSGS) as part of the GVHD. Soon after the reintroduction of previous immunosuppressive therapy, we observed a complete remission of the NS.
 ...
PMID:Nephrotic syndrome resulting from focal segmental glomerulosclerosis in a peripheral blood stem cell transplant patient. 1787 18

Hematopoietic cell transplantation-associated renal injury may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease. Renal biopsy specimens from hematopoietic cell transplant recipients at two institutions (Stanford University Medical Center and Oregon Health & Science University) were reviewed in correlation with clinical data. Fifteen cases were identified (post hematopoietic cell transplant time 0.7-14.5 years), including six with autologous hematopoietic cell transplant. Indications for renal biopsy included proteinuria (n=13; nephrotic range in 8), increased serum creatinine (n=10), or both (n=6). Many patients had multiple pathologic findings on renal biopsy. Membranous glomerulonephritis was the most common diagnosis (n=7), including two patients with autologous hematopoietic cell transplant and five with evidence of chronic graft-versus-host disease elsewhere. Four membranous glomerulonephritis patients achieved sustained remission with rituximab therapy. Other glomerular pathology included focal segmental glomerulosclerosis (n=1) and minimal change disease (n=1). Evidence of thrombotic microangiopathy was common (in isolation or combined with other pathology), as was acute tubular necrosis and tubulointerstitial nephritis. Of 14 patients with follow-up (2-64 months, mean 19 months), 6 had chronic renal insufficiency (serum creatinine >1.5 mg/dl), 2 had end stage renal disease, and 6 had essentially normal renal function. Our retrospective study shows that renal dysfunction in hematopoietic cell transplant recipients is often multifactorial, and biopsy may reveal treatable causes. Membranous glomerulonephritis is seen in autologous and allogeneic hematopoietic cell transplant recipients, and may respond to anti-B-cell therapy, which has implications regarding pathogenesis and relationship to graft-versus-host disease.
 ...
PMID:Renal pathology in hematopoietic cell transplantation recipients. 1822 56

Plasmacytoid dendritic cells play important roles in inducing immune tolerance, preventing allograft rejection, and regulating immune responses in both autoimmune disease and graft-versus-host disease. In order to evaluate a possible protective effect of plasmacytoid dendritic cells against renal inflammation and injury, we purified these cells from mouse spleens and adoptively transferred lipopolysaccharide (LPS)-treated cells, modified ex vivo, into mice with adriamycin nephropathy. These LPS-treated cells localized to the kidney cortex and the lymph nodes draining the kidney, and protected the kidney from injury during adriamycin nephropathy. Glomerulosclerosis, tubular atrophy, interstitial expansion, proteinuria, and creatinine clearance were significantly reduced in mice with adriamycin nephropathy subsequently treated with LPS-activated plasmacytoid dendritic cells as compared to the kidney injury in mice given naive plasmacytoid dendritic cells. In addition, LPS-pretreated cells, but not naive plasmacytoid dendritic cells, convert CD4+CD25- T cells into Foxp3+ regulatory T cells and suppress the proinflammatory cytokine production of endogenous renal macrophages. This may explain their ability to protect against renal injury in adriamycin nephropathy.
 ...
PMID:Lipopolysaccharide-pretreated plasmacytoid dendritic cells ameliorate experimental chronic kidney disease. 2231 23

We report a case of pediatric severe aplastic anemia (SAA), where the patient underwent allogenic bone marrow transplantation (BMT) from an HLA mismatched family donor and developed focal segmental glomerulosclerosis (FSGS). An 11-year-old girl, who had SAA, was admitted to our hospital in 200X. Complete remission was not attained after immunosuppressive therapy with rabbit-antithymocyte globulin, prednisolone (PSL), and cyclosporine A (CsA). Eight months after being diagnosed with SAA, she underwent an allogenic BMT from her mother. We used a combination of 2-Gy total body irradiation, fludarabine, and cyclophosphamide as a preparative regimen prior to the BMT. CsA and PSL were used as prophylaxis against GVHD. Since the BMT did not lead to successful engraftment, the patient required two peripheral blood stem cell transplantations (PBSCT). Engraftment was sustained and no acute or chronic GVHD was observed. Six months after the first BMT, she developed clinical nephrotic syndrome despite the continuous PSL and CsA treatments. Renal biopsy revealed a total of 12 glomeruli, one of which showed segmental sclerosis. Electron microscopy revealed diffuse effacement of the foot processes. These findings were consistent with FSGS, and she was treated with mycophenolate mofetil (MMF) in combination with PSL instead of CsA, which greatly reduced her proteinuria. In general, the most common type of nephropathy after HSCT is GVHD-related nephrotic syndrome, and the most common pathological finding is membranous nephropathy or minimal change. FSGS without GVHD after HSCT, such as that observed in our case, is rare. In this case, the renal damage appears to have been caused by the effect of circulating permeability factors with immunity change after HSCT. This case demonstrates the importance of renal biopsy as a guide to determine the extent of renal damage and as an aid to determine the possible response to therapy.
 ...
PMID:[A case of focal segmental glomerulosclerosis with nephrotic syndrome after hematopoietic stem cell transplantatation for aplastic anemia]. 2346 Dec 15

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.
 ...
PMID:Chronic graft versus host disease and nephrotic syndrome. 2519 9

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.
 ...
PMID:Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series. 2701 34


<< Previous 1 2 3 Next >>