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)

So far two methods for prolonging the tolerance of renal ischemia are available: 1) surface cooling with crushed ice and 2) perfusion cooling with an extracellular-like solution. Both methods use only the principle of reducing metabolism through cooling. While rewarming during surgery the ischemic protection is lost, or the kidney must be cooled once again. Therefore, a new preservation solution should reduce energy consumption due to its composition in addition to cooling. For open heart surgery, the HTK solution by Bretschneider is already used clinically. In 71 dog kidney experiments, the ischemic time kidneys could tolerate was prolonged by this solution from 15 to 120 min at 35 degrees C and from 45 to 360 min at 25 degrees C. After 2 h of ischemia at 30 degrees C glomerular filtration rate was about 20 ml/min.100gww within 3 h of reperfusion. After six postoperative days the filtration rate was 40 ml/min.100 gww. No ischemic damage could be recognized by histological investigations. The clinical effectiveness of this method was shown in 7 clinical applications. Ischemic duration lasted up to 113 min, and blood creatinine was between 0.8 and 2.4 mg% at the 6th postoperative day. Use of this preservation technique thus leads to improved kidney function immediately following operation. Longer ischemia can be tolerated by a kidney thus protected, and using this technique excellent visibility can be achieved during intrarenal surgery, simplifying, for example, tumor extirpation.
 ...
PMID:A new method for conservative renal surgery--experimental and first clinical results. 212 22

Several functional parameters were applied in an experimental model of ischemia to test the ability to localize the distribution of tubular lesions. Canine kidneys were perfused with protective solutions and rendered ischemic for definite periods. Renal function was determined during a subsequent 3-h reperfusion. The pattern and the extent of renal injury were influenced by varying the duration of ischemia and by modifying the protective solution used. The results suggest that by employing an appropriate selection of parameters it is possible to allocate renal injury to definite sections of the tubules. According to such an evaluation, under protection with HTK-solution, the proximal tubule limits the tolerance of renal ischemia. The thick ascending limb shows some vulnerability that is aggravated by disadvantageous modifications of the protective solution and that may become more pronounced in the course of reperfusion. In contrast, more distal parts of the nephron retain a remarkable reserve transport capacity after a tolerable level of ischemia.
 ...
PMID:Postischemic diagnostic localization of tubular lesions. 231 10

The addition of the disaccharides maltose (10, 20, 30 mM) and sucrose (30, 60 mM) to Bretschneider's organ protective HTK solution was evaluated to improve renal protection by an enhanced glycolytic energy supply. Canine kidneys were perfused for 8 min with either HTK solution or HTK solution containing additional disaccharides. After nephrectomy the kidneys were incubated at 25 degrees C and metabolic parameters were determined at regular intervals. Maltose and sucrose are slowly cleaved during renal ischemia but maltose distinctly faster than sucrose. Maltose increases intraischemic ATP supply. However, 30 mM maltose was no better than 10 mM. 60 mM sucrose was about as effective for glycolysis as 10 mM maltose. However, possibly due to fructose release there was an accelerated decrease of adenine nucleotides with sucrose. Although fructose enters glycolysis it seems to have negative side-effects. Hence, probably neither sucrose nor fructose are appropriate for renal substrate supply during ischemia.
 ...
PMID:Intraischemic metabolic effects of different disaccharides on protected canine kidneys. 251 81

Following renal ischemia under protection, the perfusion of the tubular system increases concomitant to the rise of GFR. The transport into urine of enzymes entering the tubular lumen due to ischemic injury is dependent on tubular flow. Thus, we examined if in the early postischemic phase urinary enzyme determinations can contribute to the evaluation of the ischemic injury despite the interference of a changing tubular washout. Canine kidneys were perfused with different protective solutions and subsequently rendered ischemic. From the beginning of reperfusion the endogenous creatinine clearance, the urine minute volume and the urinary LDH-concentration were determined. The urinary LDH-concentration allowed only a rough assessment of renal ischemic damage. The adjustment of the urinary LDH amounts to the GFR resulted in a better graduation according to the ischemic stress. With such a standardized LDH parameter the urinary LDH release was somewhat lower on the average when L-aspartate was added to the HTK solution in place of chloride. In conclusion, during the early postischemic recovery after renal protection the examination of the urinary enzyme release may be a useful diagnostic means for the assessment of the extent of the ischemic injury if an appropriate frame of reference is applied.
 ...
PMID:Urinary LDH-release for evaluation of postischemic renal function. 265 82

The aims of this study were (1) to investigate the effect of R 75231, a nucleoside transport inhibitor, on renin-angiotensin release after renal ischemia-reperfusion and (2) to establish a possible protective effect of this drug on renal function. We used a canine model for auto- transplantation of kidneys that had been subjected to 30 min of warm ischemia and subsequently to 24h of cold storage in HTK preservation solution, with immediate contralateral nephrectomy. R 75231 was injected intravenously into six dogs in two equal portions of 0.05 mg/kg both 30 min and 10 min before reanastomosis was established. Another six dogs were used as a control group. At 2 weeks post-transplantation, five out of six dogs in the R 75231 group and one out of six in the control group were still alive. Starting on day 4, serum creatinine was lower in the R 75231 group than in the control group (p < 0.005). In contrast to the control group, an inversion of the median preischemia adenosine/inosine ratio was observed in the R 75231 group after reperfusion (0.4 preischemia vs 4.0 after 60 min of reperfusion). Reperfusion of the graft resulted in an immediate increase in renin, angiotensin I, and angiotensin II venous blood levels in the control group. In the R 75231 group, renin, angiotension I, and angiotensin II levels were significantly lower. We conclude that administration of R 75231 before reperfusion has a protective effect on post-transplant function of kidneys that have been subjected to prolonged warm ischemia. This effect may, at least in part, be ascribed to inhibition of the breakdown and disposal of endogenous adenosine which, in turn, inhibits the excessive stimulation of the renin-angiotensin system in the early phase of reperfusion.
 ...
PMID:Protection of canine renal grafts by renin-angiotensin inhibition through nucleoside transport blockade. 762 81

Hypoxia causes several renal tubular dysfunctions, including abnormal handling of potassium and sodium and increased blood pressure. Therefore, we investigated the impact of hypoxia on 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) enzyme, a crucial prereceptor gatekeeper for renal glucocorticosteroid-mediated mineralocorticoid action. The effect of hypoxia was assessed in vitro by incubating LLC-PK1 cells with antimycin A, an inhibitor of mitochondrial oxidative phosphorylation. Antimycin A induced a dose- and time-dependent reduction of 11beta-HSD2 activity. The early growth response gene, Egr-1, a gene known to be stimulated by hypoxia was investigated because of a potential Egr-1 binding site in the promoter region of 11beta-HSD2. Antimycin A induced Egr-1 protein and Egr-1-regulated luciferase gene expression. This induction was prevented with the MAPKK inhibitor PD 98059. Overexpression of Egr-1 reduced endogenous 11beta-HSD2 activity in LLC-PK1 cells, indicating that MAPK ERK is involved in the regulation of 11beta-HSD2 in vitro. In vivo experiments in rats revealed that Egr-1 protein increases, whereas 11beta-HSD2 mRNA decreases, in kidney tissue after unilateral renal ischemia and in humans the renal activity of 11beta-HSD2 as assessed by the urinary ratio of (tetrahydrocortisol+5alpha-tetrahydrocortisol)/tetrahydrocortisone declined when volunteers were exposed to hypoxemia at high altitude up to 7000 m. Thus, hypoxia decreases 11beta-HSD2 transcription and activity by inducing Egr-1 in vivo and in vitro. This mechanism might account for enhanced renal sodium retention and hypertension associated with hypoxic conditions.
 ...
PMID:Hypoxia causes down-regulation of 11 beta-hydroxysteroid dehydrogenase type 2 by induction of Egr-1. 1262 38

Isoflurane has a pharmacological preconditioning effect against ischemia in the heart and brain, but whether this also occurs in the kidney is unclear. In this study, we investigated pharmacological preconditioning by isoflurane in the rat kidney. In the isoflurane preconditioning group (1.5% isoflurane for 20 min before renal ischemia) serum creatinine (1.2 +/- 0.7 and 1.1 +/- 0.2 mg/dL) and blood urea nitrogen (99 +/- 29 and 187 +/- 31 mg/dL) were significantly smaller at 24 and 48 h after reperfusion than in the nonpreconditioning group (creatinine; 2.4 +/- 1.2 and 2.9 +/- 0.9 mg/dL, urea; 62 +/- 19 and 79 +/- 20 mg/dL). We also investigated the intracellular signal transduction involved in isoflurane preconditioning in the kidney. The activities of the stress protein kinases, JNK and ERK but not p38, were significantly less in the kidneys of the preconditioning group than in those of the nonpreconditioning group (P < 0.05). We conclude that isoflurane has a preconditioning effect against renal ischemia/reperfusion injury when administered before ischemia. Inhibition of the protein kinases, JNK and ERK, might be involved in the mechanisms of isoflurane preconditioning.
 ...
PMID:Isoflurane protects renal function against ischemia and reperfusion through inhibition of protein kinases, JNK and ERK. 1700 Aug 48

Renal ischemia-reperfusion (IR) injury is a major clinical problem without effective therapy. We recently reported that volatile anesthetics protect against renal IR injury, in part, via their anti-inflammatory properties. In this study, we demonstrate the anti-inflammatory and antinecrotic effects of sevoflurane in cultured kidney proximal tubule cells and probed the mechanisms of sevoflurane-induced renal cellular protection. To mimic inflammation, human kidney proximal tubule (HK-2) cells were treated with tumor necrosis factor-alpha (TNF-alpha; 25 ng/ml) in the presence or absence of sevoflurane. In addition, we studied the effects of sevoflurane pretreatment on hydrogen peroxide (H2O2)-induced necrotic cell death in HK-2 or porcine proximal tubule (LLC-PK1) cells. We demonstrate that sevoflurane suppressed proinflammatory effects of TNF-alpha evidenced by attenuated upregulation of proinflammatory cytokine mRNA (TNF-alpha, MCP-1) and ICAM-1 protein and reduced nuclear translocation of the proinflammatory transcription factors NF-kappaB and AP-1. Sevoflurane reduced necrotic cell death induced with H2O2 in HK-2 cells as well as in LLC-PK1 cells. Sevoflurane treatment resulted in phosphorylation of prosurvival kinases, ERK and Akt, and increased de novo HSP-70 protein synthesis without affecting the synthesis of HSP-27 or HSP-32. We conclude that sevoflurane has direct anti-inflammatory and antinecrotic effects in vitro in a renal cell type particularly sensitive to injury following IR injury. These mechanisms may, in part, account for volatile anesthetics' protective effects against renal IR injury.
 ...
PMID:Anti-inflammatory and antinecrotic effects of the volatile anesthetic sevoflurane in kidney proximal tubule cells. 1647 75

We showed previously that activation of A(1) adenosine receptors (AR) protects against renal ischemia-reperfusion (IR) injury in rats and mice. In the heart, transient A(1)AR activation produces biphasic protective effects: acute protection wanes after several hours but protective effects return 24-72 h later (second window of protection). In this study, we determined whether A(1)AR activation produces delayed renal protection and elucidated the mechanisms of acute and delayed renal protection. A(1)AR wild-type mice were subjected to 30-min renal ischemia and 24 h of reperfusion to produce acute renal failure. Pretreatment with a selective A(1)AR agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA; 0.1 mg/kg bolus ip) either 15 min or 24 h before renal ischemia protected against renal IR injury and reduced renal corticomedullary necrosis, apoptosis, and inflammation. Transient A(1)AR activation led to phosphorylation of extracellular signal-regulated protein kinase mitogen-activated protein kinase (ERK MAPK), Akt, and heat shock protein 27 (HSP27). Moreover, induction of HSP27 and Akt occurred with CCPA treatment. Inhibition of PKC with chelerythrine prevented acute but not delayed renal protection with A(1)AR activation. Moreover, deletion of PI3Kgamma or inhibition of Akt, but not inhibition of ERK, prevented delayed and acute renal protection with A(1)AR activation. Inhibition of G(i/o) with pertussis toxin obliterated both acute and delayed A(1)AR-mediated renal protection. In contrast to renal protection with delayed ischemic preconditioning, nitric oxide synthase activity was not induced with delayed A(1)AR-mediated renal protection. Therefore, transient activation of renal A(1)AR led to acute as well as delayed protective effects against renal IR injury via distinct signaling pathways.
 ...
PMID:Acute and delayed renal protection against renal ischemia and reperfusion injury with A1 adenosine receptors. 1792 14

Several volatile anesthetics, including sevoflurane, protect against renal ischemia-reperfusion injury in vivo by reducing necrosis and inflammation. Furthermore, in cultured renal tubule cells, sevoflurane directly induced the phosphorylation of the cytoprotective kinases (ERK and Akt), upregulated 70-kDa heat shock protein (HSP70), and attenuated nuclear translocation of the proinflammatory transcription factor NF-kappaB. It has been shown that sevoflurane increases the release of transforming growth factor-beta1 (TGF-beta1) in human proximal tubule (HK-2) cells via externalization of plasma membrane phosphatidylserine (PS), and this increase in TGF-beta1 protected HK-2 cells against hydrogen peroxide-mediated necrosis. In this study, we aimed to determine whether the sevoflurane-mediated phosphorylation of ERK and Akt, induction of HSP70, and reduction in NF-kappaB activation are due to TGF-beta1 receptor-mediated signaling after PS externalization in HK-2 cells. Exogenous TGF-beta1 and a liposome mixture containing PS mimicked sevoflurane-mediated ERK and Akt phosphorylation and HSP70 induction in HK-2 cells. Sevoflurane and TGF-beta1 caused the nuclear translocation of the SMAD3 transcription factor in HK-2 cells. Furthermore, a neutralizing TGF-beta1 antibody or exogenous annexin V to bind PS prevented sevoflurane-induced ERK and Akt phosphorylation and HSP70 induction in HK-2 cells. Finally, a TGF-beta1 antibody and annexin V attenuated the reduction in nuclear translocation of NF-kappaB by sevoflurane. Therefore, we demonstrate in this study that sevoflurane-mediated cytoprotective and anti-inflammatory effects in HK-2 cells are at least partially due to the externalization of PS and activation of TGF-beta1 signaling pathways.
 ...
PMID:Sevoflurane-mediated TGF-beta1 signaling in renal proximal tubule cells. 1805 87


1 2 3 Next >>