Journal of the American Society of Nephrology : JASN
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J. Am. Soc. Nephrol. · Jan 2004
A1 adenosine receptor activation inhibits inflammation, necrosis, and apoptosis after renal ischemia-reperfusion injury in mice.
It was previously demonstrated that preischemic A(1) adenosine receptor (AR) activation protects renal function after ischemia-reperfusion (IR) injury in rats. The role of the A(1) AR in modulating inflammation, necrosis, and apoptosis in the kidney after IR renal injury was further characterized. C57BL/6 mice were subjected to 30 min of renal ischemia, with or without pretreatment with 1,3-dipropyl-8-cyclopentylxanthine or 2- chlorocyclopentyladenosine (selective A(1) AR antagonist and agonist, respectively). ⋯ C57BL/6 mice that had been pretreated with the A(1) AR agonist demonstrated significantly improved renal function and reduced expression of inflammatory markers, necrosis, and apoptosis 24 h after IR injury. In contrast, C57BL/6 mice that had been pretreated with the A(1) AR antagonist demonstrated significantly worsened renal function and increased expression of inflammatory markers, necrosis, and apoptosis. In conclusion, it was demonstrated that endogenous and exogenous preischemic activation of the A(1) AR protects against IR injury in vivo, through mechanisms that reduce inflammation, necrosis, and apoptosis.
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J. Am. Soc. Nephrol. · Apr 2003
Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome.
Acute renal failure (ARF) is a common complication in intensive care unit (ICU) patients. Although there are several reports on outcome of septic patients with ARF, there are no data regarding predisposing factors for ARF. Therefore, the incidence of ARF was investigated in 185 sepsis patients admitted in a surgical ICU during a 16-mo period. ⋯ Need for RRT was independently associated with mortality. A simple risk model for ARF, on basis of two readily available parameters on day 1 of sepsis, was developed. This model allows initiating specific therapeutic measures earlier in the course of sepsis, hopefully resulting in a lower incidence of ARF and needi for RRT, thereby lowering mortality.
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J. Am. Soc. Nephrol. · Mar 2003
Urinary concentrating defect in hypothyroid rats: role of sodium, potassium, 2-chloride co-transporter, and aquaporins.
Hypothyroidism is associated with impaired urinary concentrating ability in humans and animals. The purpose of this study was to examine protein expression of renal sodium chloride and urea transporters and aquaporins in hypothyroid rats (HT) with diminished urinary concentration as compared with euthyroid controls (CTL) and hypothyroid rats replaced with L-thyroxine (HT+T). Hypothyroidism was induced by aminotriazole administration. ⋯ Protein abundance of renal AQP1 and urea transporters UTA(1) and UTA(2) did not differ significantly among study groups. There was however a significant decrease in protein abundance of AQP2, AQP3, and AQP4 in HT rats as compared with CTL and HT+T rats. These findings demonstrate a decrease in the medullary osmotic gradient secondary to impaired countercurrent multiplication and downregulation of aquaporins 2, 3, and 4 as contributors to the urinary concentrating defect in the hypothyroid rat.
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J. Am. Soc. Nephrol. · Jan 2003
Randomized Controlled Trial Multicenter Study Clinical TrialHemodialysis infection prevention with polysporin ointment.
Hemodialysis patients in whom permanent vascular access cannot be achieved are dependent on a central venous catheter. In such patients, catheter-related infections are a common and serious complication. This study was a randomized clinical trial to determine if topical Polysporin Triple antibiotic ointment applied to the central venous catheter insertion site could reduce the incidence of catheter-related infections. ⋯ When all available follow-up information was included, the difference in survival remained significant (19 versus 9 deaths; P = 0.0027). Within the first 6 mo, infections were observed in 7 of the 13 placebo subjects who died (54%) as compared with no infections in the three Polysporin Triple subjects who died. The prophylactic application of topical Polysporin Triple antibiotic ointment to the central venous catheter insertion site reduced the rate of infections and was associated with improved survival in hemodialysis patients.
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J. Am. Soc. Nephrol. · Nov 2002
Preconditioning and adenosine protect human proximal tubule cells in an in vitro model of ischemic injury.
Renal ischemic reperfusion injury results in unacceptably high mortality and morbidity during the perioperative period. It has been recently demonstrated that ischemic preconditioning or adenosine receptor modulations attenuate renal ischemic reperfusion injury in vivo. An in vitro model of ischemic renal injury was used in cultured human proximal tubule (HK-2) cells to further elucidate the protective signaling cascades against renal ischemic reperfusion injury. ⋯ Cytoprotection by ATP depletion preconditioning or A(1) adenosine receptor activation was prevented by inhibitors of extracellular signal-regulated mitogen-activated kinases, protein kinase C, and tyrosine kinases. The A(1) and A(2a) adenosine receptor-mediated cytoprotection were also dependent on G(i/o) proteins and PKA activation, respectively. It is concluded that ATP depletion preconditioning and A(1) and A(2a) adenosine receptor activation protect HK-2 cells against severe ATP depletion injury via distinct signaling pathways.