Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Acute renal failure produced by combining cyclosporine and brief renal ischemia in the Munich Wistar rat. 370 29

These experiments were designed to determine the influence of age on the response of the kidney to ischemia. Renal ischemia was induced in female Fischer-344 rats, 3-4 or 37-38 months old, by renal arterial and venous occlusion followed by 0, 1, 24, or 96 hr of reflow. Age-matched controls were sham operated but were not subjected to ischemia. A transient postischemic increase in blood urea nitrogen (BUN) and serum creatinine was observed in young rats. In old rats, BUN and serum creatinine remained markedly elevated through 96 hr postischemia. In vitro renal cortical slice accumulation of organic ions was inhibited to a greater extent in old rats than in young rats 96 hr postischemia. Histologically, renal tubular damage was more severe in old than in young rats 24 and 96 hr postischemia. Tubular regenerative activity was similar in old and young rats at 96 hr, but restoration of tubular architecture was more complete in young rats. Organic ion accumulation by renal cortical slices from naive old rats was inhibited by in vitro anoxia (treatment with 100% N2) to a greater extent than tissue from young rats. These data suggest that old rats are more susceptible to renal ischemia than are young rats and these differences in susceptibility may reflect intrinsic age-related differences in basal renal metabolism.
 ...
PMID:Age-related differences in susceptibility to renal ischemia in rats. 382 87

This study tested the ability of the converting enzyme inhibitor, captopril, to lessen the severity of acute renal failure following temporary occlusion of the renal artery. In the control group, 11 dogs were anesthetized with halothane, and the left kidney was isolated through a midline incision. The renal artery, vein, and ureter were then clamped for 120 min. Immediately after occlusion, the kidney was flushed with 40 ml of saline at 34 degrees C. When the clamp was released, a contralateral nephrectomy was performed and the animal allowed to recover. Serum creatinine and blood urea nitrogen levels were followed on a daily basis thereafter. Thirteen captopril-treated dogs were treated in the same fashion except that captopril (1.25 ml/kg, i.v.) was given prior to the 120-min period of renal ischemia. Three of 11 (27%) control dogs survived, whereas 10 of 13 (77%) captopril-treated animals survived (P less than 0.05). Serum creatinine (5.4 +/- 2.5 mg/dl) and serum urea nitrogen (96 +/- 33 mg/dl) peaked on day 8 in the captopril-treated group and were consistently lower than in the untreated group. These observations suggest that captopril is useful when temporary interruption of the renal circulation is encountered, such as in renal autotransplantation, cadaveric renal transplantation, and renal revascularization. These data also suggest that inhibition of the renin-angiotensin system may lessen the severity of acute renal failure following renal ischemia.
 ...
PMID:Enhancement of recovery in postischemic acute renal failure with captopril. 637 20

Models of post-ischemic acute renal failure were prepared in rats. The effects of adenosine triphosphate-magnesium chloride (ATP-MgCl2) administration following renal ischemia on possible changes in renal function and renal cellular metabolism following ischemia were studied using the model. The results obtained revealed the following: 1) Over 40 minute-renal ischemia led to significant lowerings of renal cellular ATP level and energy charge (EC) by as much as 45 to 57% and 4.1 to 7.4% of the control, respectively, at 90 min following re-establishment of renal blood flow. Significant increases in Na+ in renal tissues were observed, but no changes in K+. Further, lactate level in renal tissues tended to increase with prolonged ischemic time by as much as 27 to 31% of the control, with a renal cellular anaerobic metabolism observed. On the other hand, at 24 hr following recirculation of the kidney, plasma creatinine (P-Cr), blood urea nitrogen (BUN) and fraction excretion of sodium (FENa) increased significantly, and creatinine clearance (C-Cr) and urine osmotic pressure decreased significantly, as compared with the control, indicating ischemic acute renal failure. 2) Intravenous injection of ATP-MgCl2 at a dose of 25 mumole/kg and a rate of 1.0 mumol/min after 40 min of renal ischemia led to significant lowerings of P-Cr, BUN and FENa to 36, 35 and 35% of the control (injected with physiological saline solution), respectively, and to significant elevation of C-Cr and urine osmotic pressure by as much as 41 to 31% of the control respectively, at 24 hr after reperfusion. The above results suggested that the ischemic acute renal failure was caused by the decreases in renal cellular ATP and EC with ischemia, resulting in renal cellular metabolic disturbances. It was further suggested that ATP-MgCl2 administered for such a pathological condition could make significant improvements in renal function.
 ...
PMID:[Effect of adenosine triphosphate-magnesium chloride administration for post-ischemic acute renal failure (I)]. 660 69

This study investigates the role of verapamil, a calcium channel blocker, combined with allopurinol, a xanthine-oxidase inhibitor, when given at reperfusion after severe renal ischemia injury in the rat. Male Sprague-Dawley rats were subjected to 60 minutes of warm ischemia by cross clamping the whole left renal pedicle (artery and vein). At the end of ischemia, the clamps were removed and a contralateral nephrectomy was performed. The animals (n = 40 per group) were divided into five groups; Group 1, ischemic control (IC) receiving lactated Ringer's; Group 2, allopurinol (A) 100 mg/kg; Group 3, verapamil (V) 1.25 mg/kg; Group 4, receiving a combination of A + V at the same concentrations; and Group 5, sham group. Each drug was given intravenously at the end of the ischemic period at reperfusion. Survival was evaluated at 7 days. Renal damage was assessed by kidney function tests (serum creatinine and blood urea nitrogen, or BUN), light histology. Lipid peroxidation was measured in renal tissue using the TBA (thiobarbituric acid) assay. The best survival rate was seen in the combination group of A + V (70% at 7 days; p < .01 vs. control). Single drugs were not as effective as the combination when compared to the IC. Serum creatinine at 24 and 48 hours showed a significant difference between the IC and treatment groups. At 72 hours there were no differences among the treated groups. Histological damage was more pronounced in the IC (Grade 4.0) than in the allopurinol (3.4 +/- 0.8), verapamil (3.0), or A + V (2.2 +/- 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Protective effect of combined allopurinol and verapamil given at reperfusion in severe renal ischemia. 773 32

Endocytosis in the renal tubular cell is a permanent process serving the role of saving nitrogen from plasma peptides that are continuously cleared away by kidney glomerulus. Since small proteins appear in urine after strenuous exercise, it was hypothesized that renal ischemia impairs the tubular endocytic reabsorption of proteins. The aim of this paper is to describe a simple in vitro model of renal endocytosis and to use it in studies of endocytic metabolic requirements. The results show that rabbit renal proximal tubules in suspension are able to take up 125I-lysozyme, as well as RITC-lactalbumin. The fluorescent protein was taken up only by the ends of the everted tubule fragments, and accumulated into intracellular vesicles, demonstrating the luminal pathway of endocytosis. The amount of 125I-lysozyme taken up was equivalent to that taken up by isolated perfused tubules (Nielsen et al. (1986) Am. J. Physiol. 251, F822-F830). Anoxia decreased 12-fold the intracellular accumulation of 125I-lysozyme; however, the time-course of inhibition shows that only the late steps of endocytic accumulation are energy-dependent. Substrate deprivation studies suggest a specific role of glucose to sustain endocytosis. Lastly, renal uptake of 125I-lysozyme was shown to be strongly depressed by chloroquine, an alkalinizing agent of endosomes and lysosomes. We conclude that (1) renal tubules in suspension are a satisfactory model for endocytic studies in kidney; (2) suppressing oxygen and substrate supplies to kidney impairs endocytic tubular reabsorption of proteins.
 ...
PMID:Protein endocytosis by a kidney tubule suspension: metabolic requirements. 829 19

The postischemic acute renal failure is one of the most important and frequent complications after surgery for renal artery and thoracoabdominal aortic diseases. In a canine model we studied the possible beneficial effects of Prostaglandin E1 (PGE1), Diltiazem and Superoxiddismutase (SOD) on postischemic renal function. 46 dogs were exposed to 3 hours ischemia. In 35 dogs PGE1 (n = 10), Diltiazem (n = 10), Superoxiddismutase (n = 10) or both PGE1 and SOD (n = 5) were given intravenously. 11 dogs treated with normal saline served as controls. Glomerular filtration rate, renal plasma flow, plasma creatinine, blood urea nitrogen, urine volume, free water clearance and renovascular resistance were calculated before and after renal ischemia. Radionuclide studies were performed on the third postoperative day. Two weeks later clearance measurements were repeated and kidneys were removed for histology. PGE1, Diltiazem and SOD significantly attenuated the post-ischemic fall in glomerular filtration rate and renal concentrating ability as well as the postischemic changes of tubular epithelium on histology.
 ...
PMID:[The role of pharmacologic kidney protection in preventing post-ischemic renal failure in animal experiment]. 837 23

Prolonged intraoperative renal ischemia requires modalities to reduce the incidence of acute tubular necrosis, but there exists no definitive prophylactic regimen. We studied the effects of enalaprilat, an angiotensin-converting enzyme inhibitor, in an attempt to identify such a protective drug. Thirty-four mongrel dogs underwent 90 min of bilateral renal pedicle clamping. Group I was a control of 6 animals. Group II comprised 10 animals who received 12.5 g iv mannitol 15 min prior to clamping and 1 mg/kg iv furosemide immediately after clamp removal. Group III also comprised 10 animals who received enalaprilat 1 mg/kg iv enalaprilat each 15 min prior to clamp placement. Group IV consisted of 8 dogs, each of which received 12.5 g mannitol and 1 mg/kg iv enalaprilat 15 min prior to clamping and 1 mg/kg iv furosemide immediately upon removal of the clamps. Serum blood urea nitrogen (BUN) and creatinine levels were drawn preoperatively and at 12, 24, 48, and 72 hr postoperatively in each animal. The serum BUN levels in group III were significantly lower than those in group I at all times postoperatively (P < 0.05) and were not significantly different from those of group II at any time postoperatively. Similarly, the serum creatinine levels in group III were significantly lower than those of group I (P < 0.05) and were not significantly different from those in group II at any time postoperatively. Neither the serum BUN nor the serum creatinine levels in group IV were different from those of group I at any time postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Protective effects of enalaprilat against postischemic renal failure. 838 87

NSAIDs pose little threat of renal insult in normal, healthy persons at therapeutic dosages. However, NSAID administration to susceptible persons may cause decrements in renal plasma flow and glomerular filtration rate within hours. Such acute noxious renal effects are mediated by products of arachidonic acid metabolism. Precipitous decrements in glomerular filtration and renal ischemia, manifested by increased serum creatinine and urea nitrogen, are possible. However, these effects are usually fully reversible with prompt discontinuation of the offending NSAID. Risk factors for the development of these acute renal effects are known. Acute interstitial nephritis with or without nephrotic syndrome is a rare form of renal toxicity that typically occurs between 2-18 months of use. Renal impairment may be so severe as to require temporary hemodialysis; however, renal function usually returns to normal upon discontinuation of the NSAID. The mechanism of acute interstitial nephritis is presumed to be of allergic origin but could also be caused by a reactive metabolite. Fenoprofen use appears to be associated with a much higher risk for its development. In contrast to the acute effects of NSAIDs, irreversible, analgesic-associated nephropathy manifested by papillary necrosis and chronic interstitial nephritis may occur following months to years of high doses of analgesic mixtures. The mechanism by which combination analgesics produce this form of renal injury is unknown and could be either a result of medullary ischemia or a direct effect of a reactive metabolite. An important issue to be resolved is the relationship between the acute, reversible, prostaglandin-mediated renal effects of the NSAIDs and chronic, irreversible destruction, if such a relationship exists. Theoretically, continual or repeated decrements in renal function in patients with predisposing risk factors could cause or contribute to progressive deterioration in renal function. Elevations in blood pressure or interference with the effects of antihypertensive medications could theoretically also contribute to long-term renal deterioration. In addition to renal syndromes caused by NSAIDs that result in renal impairment, other transient effects on electrolyte and water metabolism may also occur. Reduced secretion of sodium may result in formation of edema, exacerbation of heart failure, or increased blood pressure. Hyporeninemic-hypoaldosteronism may produce hyperkalemia. Finally, reduced excretion of water has rarely caused hyponatremia. It has been suggested that NSAIDs may be renoprotective in patients with nephrotic syndrome. Others have suggested that sulindac is "renal-sparing" because of a unique metabolic pathway that supposedly limits the exposure of the kidney to the active sulfide metabolite.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Renal toxicity of the nonsteroidal anti-inflammatory drugs. 849 47

Defibrotide (Df) has been reported to protect various organs from ischemic damage. The aim of this study was to evaluate the effect of Df on renal function and morphology after warm kidney ischemia. Divided into two groups, 14 pigs underwent bilateral renal clamping for 90 min. One group (7 pigs) was treated with Df (32 mg/kg per h) for 6 h, whereas the control group received 5000 IU of heparin. Serum levels of blood urea nitrogen (BUN) and creatinine measured for 6 days were significantly higher in the control group (peak 26.8 +/- 16.7 vs 11.0 +/- 2.9 mmol/l and 501.2 +/- 351.4 vs 230.2 +/- 68.0 mumol/l P < 0.05). Renal biopsy evidenced a lesser extent of tubular and endothelial damage in Df-treated animals. In conclusion, Df provided relevant protection against renal ischemic injury.
 ...
PMID:Functional and morphological effects of defibrotide on renal ischemia. 851 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>