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)

Platelet-derived growth factor (PDGF) has been proved to play an important role in progressive glomerular disease of systemic lupus. The present study investigated the tyrosine kinase inhibitor of PDGF receptor, imatinib, as a novel therapeutic approach for the cure of lupus nephritis in New Zealand Black/White (NZB/W)F1 hybrid mice with established disease. Two groups of NZB/W mice (N=30 each group), starting at 5 months of age, were given by gavage vehicle or imatinib (50 mg/kg b.i.d). Fifteen mice for each group were used for the survival study. The remaining were killed at 8 months. Imatinib significantly (P=0.0022) ameliorated animal survival with respect to vehicle. The drug significantly delayed the onset of proteinuria (% proteinuric mice, 7 and 8 months: 33 and 47 vs vehicle, 80 and 87, P<0.05) and limited the impairment of renal function. Imatinib protected the kidney against glomerular hypercellularity and deposits, tubulointerstitial damage, and accumulation of F4/80-positive mononuclear cells and alpha-smooth actin-positive myofibroblasts. The abnormal transforming growth factor-beta mRNA expression in kidneys of lupus mice was reduced by imatinib. In conclusion, findings of amelioration of animal survival and renal manifestations in NZB/W lupus mice with established disease by imatinib suggests the possibility to explore whether imatinib may function as steroid-sparing drug in human lupus nephritis.
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PMID:Imatinib ameliorates renal disease and survival in murine lupus autoimmune disease. 1668 13

Imatinib is a selective tyrosine kinase inhibitor that can block activity of the platelet-derived growth factor receptor (PDGFR) and that has immunomodulatory effects on various cell types. Here we measured the protective effects of imatinib in Wistar-Kyoto rats with nephrotoxic serum nephritis, a kidney disease model where CD8+ T cells and macrophages play pathogenetic roles. Groups of animals were given imatinib from one day before up to 13 days following induction of nephritis and from day 7 to 20 following disease induction. Compared to control rats, at each time point imatinib treatment caused significantly less proteinuria, lowered serum blood urea nitrogen and creatinine, and decreased the number of glomeruli with necrosis, crescents, and fibrin deposits. Imatinib-treated rats had a significant reduction in glomerular macrophage accumulation and reduced renal cortical PDGFR-beta and M-CSF receptor mRNA expression. Using colocalization we found that glomerular macrophages had reduced IL-1beta and MCP-1 protein expression. Late imatinib treatment significantly reduced proteinuria, serum blood urea nitrogen, and creatinine, and reversed renal histopathological changes. We show that imatinib has renoprotective and therapeutic properties and provide pre-clinical work that will need to be confirmed in patients with crescentic glomerulonephritis.
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PMID:Preventive and therapeutic effects of imatinib in Wistar-Kyoto rats with anti-glomerular basement membrane glomerulonephritis. 1924 5

Cryoglobulinemia is a systemic immune complex-mediated vasculitis that can have significant morbidity and mortality. The current treatment for cryoglobulinemia, including chlorambucil, steroids, plasmapheresis, and rituximab, is lacking in terms of efficacy, safety, and relapse rates. Imatinib, a tyrosine kinase inhibitor, has been shown to ameliorate the phenotype and kidney injury in a thymic stromal lymphopoietin transgenic mouse model of cryoglobulinemia. We present a case of type II cryoglobulinemia with severe kidney involvement treated with 400 mg of imatinib administered orally daily, plasmapheresis, and steroids, initially with resolution of symptoms, normalization of creatinine level, and marked improvement in proteinuria and cryocrit. Furthermore, on withdrawal of imatinib therapy, proteinuria, creatinine level, and cryocrit worsened until reinstitution of therapy. After treatment resumption, creatinine level, cryocrit, proteinuria, and symptoms dramatically improved and have remained stable for more than 22 months.
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PMID:Imatinib therapy for non-infection-related type II cryoglobulinemia with membranoproliferative glomerulonephritis. 2198 57