کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5844130 | 1127554 | 2009 | 20 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Therapeutic role of sirolimus in non-transplant kidney disease
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کلمات کلیدی
CDKFKBP-124E-BPsS6KCD2-associated proteinCD2APADPKDFSGSGFRCNIAMPKEGFCTGFRMEAKIHIF-1αacute kidney injury - آسیب حاد کلیهautosomal dominant polycystic kidney disease - بیماری کلیوی پلی کیستیک غالب در اتواسوم غالب استepidermal growth factor - عامل رشد اپیدرمیConnective tissue growth factor - فاکتور رشد بافت همبندcalcineurin inhibitor - مهار کننده کالسینورینCAN - می توانElite - نخبهGlomerular filtration rate - نرخ فیلتراسیون گلومرولیchronic allograft nephropathy - نفروپاتی آلرژیک مزمنPolycystin - پلیسیستینAMP-activated kinase - کیناز فعال AMPcyclin-dependent kinase - کییناز وابسته به سیکلینFocal segmental glomerulosclerosis - گلومرول اسکلروز بخش مرکزی فوکوسReceptor mediated endocytosis - گیرنده mediated endocytosis
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
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چکیده انگلیسی
Sirolimus is a member of a novel class of immunosuppressant drug that potently suppresses T cell proliferation and expansion by inhibition of the Target of Rapamycin Complex 1 (TORC1) protein kinase. Sirolimus also has anti-proliferative effects on intrinsic cells of the kidney, and increasing evidence suggests that it may have a therapeutic role in non-transplant renal diseases. In the normal kidney, sirolimus is considered to be non-nephrotoxic. In the diseased kidney, sirolimus may be beneficial or detrimental, depending on the type of renal injury. In polycystic kidney disease, TORC1 activation mediates renal tubular epithelial cell (TEC) proliferation and cyst growth in animals, and Phase III clinical trials are underway to determine the effect of sirolimus in attenuating disease progression in humans. In contrast, in acute kidney injury, sirolimus transiently impairs proximal TEC regeneration and delays renal recovery. In animal models of lupus nephritis and diabetic kidney disease, sirolimus prevents disease progression. However, the efficacy of sirolimus in human glomerulonephritis as well as in diabetic chronic kidney disease remains unclear, as it paradoxically exacerbates renal dysfunction when the baseline glomerular filtration rate is low (< 40Â ml/min/1.73Â m2) and there is heavy proteinuria (> 300Â mg/day). This may, in part, be due to inhibition of compensatory glomerular capillary repair through the suppression of endothelial cell proliferation and angiogenic growth factor production by podocytes. Therefore, at present, polycystic kidney disease is the most promising therapeutic application for sirolimus in non-transplant renal diseases, and further studies are needed to clarify its role in other situations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacology & Therapeutics - Volume 123, Issue 2, August 2009, Pages 187-206
Journal: Pharmacology & Therapeutics - Volume 123, Issue 2, August 2009, Pages 187-206
نویسندگان
Gopala K. Rangan, Tina Nguyen, Rahul Mainra, Lena Succar, Kristina G. Schwensen, Jane S. Burgess, Kok On Ho,