Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Palifermin (recombinant human keratinocyte growth factor) prevents the development of acute, lethal graft-versus-host disease (GVHD). It does so, at least in part, by protecting cells from injury. Another property of Palifermin is immune regulation. How the latter influences the evolution of GVHD remains uncertain. We explored the effect of Palifermin on GVHD in the DBA/2 --> ((DBA/2)x(C57BL/6))F(1)-hybrid strain combination, a model associated with autoantibody production and glomerulonephritis. Untreated recipients survived until at least day 150 post-induction. Palifermin-treated recipients succumbed between days 50 and 90 with levels of proteinuria of up to 20 g/L, ascites, and rapidly progressive, crescentic glomerulonephritis that was most severe in mice with the greatest levels of proteinuria. Kidney sections from both Palifermin-treated and untreated recipients showed the presence of granular deposits of IgG, IgM, IgA, and C3 in the mesangium and the glomerular basement membrane. Electron microscopy confirmed the extensive glomerular immune complex deposition. Antinuclear and anti-dsDNA antibodies were present in sera from both treated and untreated recipients; however, those in the latter were only detectable if the serum was kept at 37 degrees C, indicating that they were cryoglobulins. IL-4 was detectable only in cultures from Palifermin-treated recipients and the levels of IL-5 and IL-13 were significantly higher in the Palifermin-treated group than in untreated GVHD mice. IFN-gamma was only detectable in untreated GVHD mice. These data suggest that although Palifermin can protect mice with acute GVHD, it exacerbates GVHD in a model associated with autoantibody production and a preponderance of Th2 cytokines.
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PMID:Effect of palifermin in a murine model of graft-versus-host disease (GVHD) associated with Th2 cytokine production, autoantibody production, and glomerulonephritis. 1695 10

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.
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PMID:Focal segmental glomerulosclerosis after membranous glomerulonephritis in remission: temporal diversity of glomerulopathy after bone marrow transplantation. 1702 Jul 80

Roquinimex is an immunomodulator that can effectively inhibit the development of several autoimmune diseases in animal models, but the mechanism is still unknown. In this study, we investigated the effect of roquinimex on chronic graft-versus-host disease (GVHD) in mice, a well-established model for human systemic lupus erythematosus (SLE). Oral administration of roquinimex significantly suppressed the development of proteinuria and ameliorated nephritis symptoms in chronic GVHD mice. In addition, renal histopathology and immunohistochemistry studies revealed reduced glomerulonephritis and decreased IgG deposition in chronic GVHD mice treated with roquinimex. Chronic GVHD is characterized by a predominance of Th2 cytokines, and proinflammatory cytokines that also play an important role in the pathology of tissue damage. Therefore, we focused on the effect of roquinimex on cytokine production. Chronic GVHD mouse splenocytes exhibited severely reduced interferon (IFN)-gamma production in response to Concanavalin (Con A) stimulation and an overt Th2 skewness. Roquinimex treatment, however, induced IFN-gamma production and restored the Th1/Th2 cytokine balance, although only a minimal effect of roquinimex on interleukin (IL)-4 secretion was observed. The production of the proinflammatory cytokines TNF-alpha and IL-1 beta by peritoneal macrophages from lipopolysaccharide (LPS)-treated GVHD mice was significantly inhibited by roquinimex treatment. These data suggested that the beneficial effect of roquinimex on lupus might, at least in part, result from a restoration of Th1/Th2 cytokine balance and inhibition of inflammatory cytokine production.
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PMID:Roquinimex-mediated protection effect on the development of chronic graft-versus-host disease in mice is associated with induction of Th1 cytokine production and inhibition of proinflammatory cytokine production. 1795 Mar 63

Graft-versus-host disease is one of the most frequent complications occurring after haematopoietic stem cell transplantation. Recently, renal involvement has been described as a manifestation of chronic graft-versus-host disease. Immunosuppression seems to play a major role: clinical disease is triggered by its tapering and resolution is achieved with the resumption of the immunosuppressive therapy. Prognosis is apparently favourable, but long term follow up data are lacking.We report a case of a 53-year-old man who developed nephrotic syndrome 142 days after allogeneic stem cell transplantation for acute myeloid leukaemia. Onset of nephrotic syndrome occurred after reduction of immunosuppressants and was accompanied by manifestations of chronic graft-versus-host disease. Histological examination of the kidney was consistent with Minimal Change Disease. After treatment with prednisolone and mycophenolate mofetil he had complete remission of proteinuria and improvement of graft-versus-host disease. Eighteen months after transplantation the patient keeps haematological remission and normal renal function, without proteinuria.Since patients with chronic graft-versus-host disease might be considered at risk for development of nephrotic syndrome, careful monitoring of renal parameters, namely proteinuria, is advisable.
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PMID:Minimal change nephrotic syndrome after stem cell transplantation: a case report and literature review. 1797 Nov 94

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.
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PMID:Renal pathology in hematopoietic cell transplantation recipients. 1822 56

Advances in hematopoietic stem cell transplantation (HSCT) for beta-thalassemia major make the long-term outcome of these patients very important. Few data on long-term renal function of thalassemia patients are available. We evaluated the renal function in children after successful allogeneic HSCT for beta-thalassemia. Twenty-nine patients were included; the mean age at HSCT was 4.9 years. Mean follow-up time was 7.6 years. After HSCT, two patients developed acute renal failure and two had graft versus host disease. At last follow up, height standard deviation score (SDS) remained the same, but weight SDS had improved. Mean hemoglobin was 12.5 g/dl, and serum ferritin level was 545 ng/ml. All children had normal estimated glomerular filtration rate (GFR). One patient had hypertension and proteinuria, 10 years after HSCT. When comparing 39 children of the same age with beta-thalassemia of similar disease severity but who had not experienced HSCT, we found that the parameters of renal tubule function were better in patients that had undergone HSCT, as demonstrated by urine protein level (0.36 mg/mg creatinine vs 3.03 mg/mg creatinine, P < 0.001), osmolality (712 mosmol/kg vs 573 mosmol/kg, P = 0.006), N-acetyl-beta-D: -glucosaminidase (17.7 U/g creatinine vs 42.9 U/g creatinine, P = 0.045), and beta 2 microglobulin (0.09 microg/mg creatinine vs 0.13 microg/mg creatinine, P = 0.029). This study showed a low incidence of long-term renal impairment after HSCT and indicated that renal tubule function may be better in beta-thalassemia patients after HSCT.
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PMID:Renal tubule function in beta-thalassemia after hematopoietic stem cell transplantation. 1868 53

Chronic kidney disease (CKD) is common after hematopoietic cell transplantation (HCT). We prospectively measured the urinary albumin:creatinine ratio (ACR) in 142 patients. Total (intact) monomeric albumin was determined by liquid chromatography of untreated urine samples collected weekly to day 100 after HCT. Albuminuria was defined as ACR (mg/g creatinine) > 30; proteinuria, as ACR >300. Cox and logistic regression analyses evaluated ACR as a risk factor for clinical events. The prevalence of albuminuria was 37% at baseline, 64% at day 100, and 50% at 1 year. Proteinuria occurred in 4% of patients at baseline, in 15% at day 100, and in 4% at 1 year. Characteristics associated with albuminuria include age, sex, donor type, hypertension, and sinusoidal obstruction syndrome (SOS). Albuminuria was associated with an increased risk of acute graft-versus-host disease (aGVHD) and bacteremia, but not acute kidney injury (AKI). Albuminuria at day 100 was associated with CKD at 1 year (odds ratio = 4.0; 95% confidence interval [CI] = 1.1 to 14.6). Nonrelapse mortality (NRM) risk was elevated (hazard ratio = 6.8; 95% CI = 1.1 to 41.5) in patients with overt proteinuria at day 100. Albuminuria occurs frequently after HCT and is correlated with aGVHD, bacteremia, hypertension, and progression of renal disease. Proteinuria at day 100 is associated with an 6-fold increased risk of NRM by 1 year after HCT.
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PMID:Albuminuria in hematopoietic cell transplantation patients: prevalence, clinical associations, and impact on survival. 1904 Oct 58

Membranous glomerulonephritis and minimal change disease are the most common forms of glomerular diseases noted in patients with graft versus host disease after hematopoietic stem cell transplantation. Herein, we report a patient who developed anti-neutrophil cytoplasmic antibody associated crescentic IgA nephropathy within 3 months after autologous hematopoietic stem cell transplantation. He was treated with intravenous pulse steroids and monthly intravenous cyclophosphamide for 6 months followed by cyclophosphamide every 3 months and tapering dose of steroids. His proteinuria resolved and renal function remained stable. Two cases of crescentic IgA nephropathy have been reported in patients who underwent allogenic hematopoietic stem cell transplantation. The etiology of IgA nephropathy developing after hematopoietic stem cell transplantation is unclear and larger registry-based studies are needed to further explore this condition.
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PMID:Anti-neutrophil cytoplasmic antibody associated crescentic IgA nephropathy in hematopoietic stem cell transplantation. 1920 51

Mesenchymal stem cell (MSC) therapy has shown promise clinically in graft-versus-host disease and in preclinical animal models of T helper type 1 (Th1)-driven autoimmune diseases, but whether MSCs can be used to treat autoimmune disease in general is unclear. Here, the therapeutic potential of MSCs was tested in the New Zealand black (NZB)xNew Zealand white (NZW) F1 (NZB/W) lupus mouse model. The pathogenesis of systemic lupus erythematosus involves abnormal B and T cell activation leading to autoantibody formation. To test whether the immunomodulatory activity of MSCs would inhibit the development of autoimmune responses and provide a therapeutic benefit, NZB/W mice were treated with Balb/c-derived allogeneic MSCs starting before or after disease onset. Systemic MSC administration worsened disease and enhanced anti-double-stranded DNA (dsDNA) autoantibody production. The increase in autoantibody titres was accompanied by an increase in plasma cells in the bone marrow, an increase in glomerular immune complex deposition, more severe kidney pathology, and greater proteinuria. Co-culturing MSCs with plasma cells purified from NZB/W mice led to an increase in immunoglobulin G antibody production, suggesting that MSCs might be augmenting plasma cell survival and function in MSC-treated animals. Our results suggest that MSC therapy may not be beneficial in Th2-type T cell- and B cell-driven diseases such as lupus and highlight the need to understand further the appropriate application of MSC therapy.
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PMID:Allogeneic mesenchymal stem cells do not protect NZBxNZW F1 mice from developing lupus disease. 2045 9

Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation has been increasingly described as a manifestation of chronic graft-versus-host disease (GVHD); however, GVHD-associated membranoproliferative glomerulonephritis is extremely rare. A 44-year-old man developed nephrotic syndrome 24 months after HSCT for acute lymphoblastic leukemia. The renal biopsy showed type I membranoproliferative glomerulonephritis. Salivary gland biopsy demonstrated mild lymphocytic infiltration, indicating chronic GVHD. Improvement of the proteinuria and recovery of renal function were achieved within 11 months of treatment with oral prednisolone and azathioprine.
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PMID:Membranoproliferative glomerulonephritis following allogeneic hematopoietic stem cell transplantation. 2080 9


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