Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal tubular cells die by apoptosis as well as necrosis in experimental models of ischemic and toxic acute renal failure as well as in humans with acute tubular necrosis. It is not yet possible, however, to determine the relative contribution of these two forms of cell death to loss of renal tubular cells in acute tubular necrosis. The beneficial effect of administering growth factors to animals with acute tubular necrosis is probably related to the potent antiapoptotic (survival) effects of growth factors as well as to their proliferative effects. Rapamycin inhibits both of these effects of growth factors and delays the recovery of renal function after acute tubular necrosis by inhibiting renal tubular cell regeneration and by increasing renal tubular cell loss by apoptosis. The administration of caspase inhibitors ameliorates ischemia-reperfusion injury in multiple organs including the kidney. However, the extent to which this protective effect of caspase inhibition is caused by reduced intrarenal inflammation, or by amelioration of renal tubular cell loss due to apoptosis, remains uncertain. In addition to caspase inhibition, the apoptotic pathway offers many potential targets for therapeutic interventions to prevent renal tubular cell apoptosis.
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PMID:Role of apoptosis in the pathogenesis of acute renal failure. 1198 Dec 60

Late spontaneous kidney graft decapsulation with fluid collection is a rare condition with only a few cases reported in the literature. Common causes of renal allograft rupture include acute rejection, acute tubular necrosis, renal vein thrombosis, and trauma. Sirolimus related late spontaneous decapsulation has not been reported in the past. Interestingly, sirolimus may promote lymphocele formation in renal transplant recipients, including those presenting with chronic hepatitis B or C. Herein, we report a case of late spontaneous decapsulation with subcapsular hematoma formation developing 12 years after receipt of a cadaveric allograft. The patient was infected with both hepatitis B and C viruses. Cyclosporine was replaced by sirolimus for maintenance therapy because of chronic rejection and acute deterioration of renal function. He presented to the hospital at 9 months after sirolimus inception because of a sudden onset of pain and swelling over the kidney graft. Magnetic resonance imaging found the capsule to be stripped from the kidney by a collection of liquefied hematomas. A laparoscopic fenestration was performed by creation of a peritoneal window adjacent to the renal allograft. When patients have chronic hepatitis, tacrolimus might be a better choice than sirolimus.
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PMID:Late spontaneous kidney graft decapsulation after administration of sirolimus in a recipient with chronic hepatitis B and C infection: a case report. 1879 Feb 60

Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA) on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 nanog/mL); CsA (100 microg/mL); sirolimus (50 and 250 nanog/mL) + CsA (100 microg/mL); control; vehicle (20% ethanol). For in vivo studies, 3-week-old Wistar rats (150-250 g) were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I) in five groups: sham, I, I + SRL (3 mg x kg(-1) x day(-1), po), I + CsA (3 mg x kg(-1) x day(-1), sc), I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR) at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 +/- 0.1 mL/min) but not in rats receiving sirolimus + CsA (0.8 +/- 0.1 mL/min) despite the reduction in renal blood flow (3.9 +/- 0.5 mL/min). Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.
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PMID:Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury. 2054 36