Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the combined effects of a brief ischemic insult and cyclosporine, four groups of male Munich Wistar rats were given: a) parenteral cyclosporine (60 mg/kg i.p.) for 4 days following 20 minutes of bilateral renal ischemia, b) the castor oil cyclosporine vehicle in a comparable volume and the same ischemic insult, c) saline in the same volume and ischemia, or d) saline and sham surgery. The cyclosporine animals ate and drank poorly, and therefore the other groups were pair-fed and watered with them. The cyclosporine-ischemia group developed significant renal failure. The other groups exhibited only a mild rise in blood urea nitrogen. Tubular vacuolization was a prominent feature in the cyclosporine and vehicle groups, but not in the saline groups. Vacuolization was correlated with severity of renal impairment. Lipid stains showed that many of the vacuoles contained lipid. Eosinophilic cytoplasmic inclusions were seen only in the cyclosporine or vehicle- (castor oil) treated animals. These findings emphasize the probable functional importance of tubular lesions in cyclosporine-induced acute renal failure, and suggest that the castor oil vehicle of parenteral cyclosporine may have renal effects of its own.
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PMID:Acute renal failure produced by combining cyclosporine and brief renal ischemia in the Munich Wistar rat. 370 29

The mechanism of clinical cyclosporine nephrotoxicity has remained unclear. We have established an animal model of cyclosporine-induced acute renal failure in the male Munich-Wistar rat by giving four daily doses of parenteral cyclosporine 60 mg/kg intraperitoneally (IP). In this model, 20 minutes of bilateral renal ischemia preceding the first cyclosporine dose did not significantly increase the renal failure, but did increase mortality (65% v 17%), which was due in part to the CNS effect of cyclosporine. Pair-fed and pair-watered vehicle and saline controls were used. The renal morphologic changes induced by the castor oil vehicle of the commercial parenteral cyclosporine solution were quantitatively similar to those induced by cyclosporine, although the severity of the changes by light microscopy was considerably less in the vehicle-treated groups. However, by electron microscopy, pale lipid vacuoles were seen only in the cyclosporine-treated groups, whereas dense alterations in lysosomes and dilated endoplasmic reticulum were also seen in other groups. Renal blood flow determined by electromagnetic flow probe showed a significant decline during 2 hours after a single IP injection of cyclosporine (6.6 +/- 0.4 to 5.0 +/- 0.6 mL/min). A similar decline was seen following injection of the castor oil vehicle of the commercial cyclosporine parenteral preparation (6.6 +/- 0.5 to 5.1 +/- 0.5 mL/min), but not after an injection of a similar volume of mineral oil (6.7 +/- 0.3 to 6.3 +/- 0.2 mL/min). These studies suggest that brief renal ischemia does not increase cyclosporine nephrotoxicity significantly in this rat model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal blood flow, glomerular filtration rate, and renal morphology in cyclosporine-induced acute renal failure in Munich-Wistar rats. 378 71

It has been difficult to produce a good animal model for cyclosporine nephrotoxicity. It has been suggested that by following 20 minutes of renal ischemia with four daily doses of cyclosporine 60 mg/kg intraperitoneally, one can create a model of reproducible renal failure. We observed excessive mortality (65%), due in part to cyclosporine's CNS effects, with these combined insults in the Munich Wistar rat. In contrast, cyclosporine alone in this dosage produced only 17% mortality and resulted in a similar degree of renal failure. Pair-fed and pair-watered vehicle and saline controls were used. The morphologic changes brought about by the castor oil vehicle of the parenteral cyclosporine solution were qualitatively similar to those brought about by cyclosporine by light microscopy, although the severity of the changes was considerably less in the vehicle-treated groups. However, by electron microscopy, pale lipid vacuoles were seen only in the cyclosporine-treated groups, whereas dense alterations in lysosomes and dilated endoplasmic reticulum also were seen in other groups. Urine sodium determined by flame photometry and urine chloride determined by Saltex reagent strips tended to be high in the initiation phase of cyclosporine-induced acute renal failure and low in the maintenance phase. In animals that developed acute renal failure following the combination of ischemia and cyclosporine, the initial urine sodium and chloride were significantly correlated with the eventual degree of renal failure. The use of Saltex urine chloride sticks in clinical urine samples showed that the readings correlated well with urine sodium and chloride determined by conventional methods, suggesting that these strips may be useful in making a quick diagnosis in the setting of acute renal failure.
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PMID:Renal morphology and function and urine electrolytes in experimental acute renal failure produced by cyclosporine and ischemia. 384 27