Kidney international
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Kidney international · May 2009
Sequential evaluation of prognostic models in the early diagnosis of acute kidney injury in the intensive care unit.
General and specific severity scores for patients with acute kidney injury have significant limitations due in part to the diversity of methods that have been used. Here we prospectively validated five general (APACHE II, SAPS II, SOFA, LODS, and OSF) and three specific (SHARF, Liaño, and Mehta) scoring systems in 366 critically ill patients who developed acute kidney injury in the intensive care unit. Sequential scores in each system were determined on the day that acute kidney injury was diagnosed, on the day when acute kidney injury-specific score criteria were achieved, and on the day of initial nephrology consultation. ⋯ On the day of initial nephrology consultation, most scores showed a good performance and two indices (SAPS II and SHARF) achieved an area under the receiver operating characteristic curve above 0.80. Calibration was good on all three defining days, except for OSF when score criteria were achieved, and Mehta at the time of nephrology consultation. Our study shows that early and sequential evaluation is a better approach for prognostic scoring in critically ill patients who develop acute kidney injury.
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Kidney international · Apr 2009
Kidney-specific reconstitution of the A1 adenosine receptor in A1 adenosine receptor knockout mice reduces renal ischemia-reperfusion injury.
Genetic deletion of the adenosine A1 receptor (A1AR) increased renal injury following ischemia-reperfusion injury suggesting that receptor activation is protective in vivo. Here we tested this hypothesis by expressing the human-A(1)AR in A(1)AR knockout mice. Renal ischemia-reperfusion was induced in knockout mice 2 days after intrarenal injection of saline or a lentivirus encoding enhanced green fluorescent protein (EGFP) or EGFP-human-A(1)AR. ⋯ Additionally, there were marked disruptions of the proximal tubule epithelial filamentous (F)-actin cytoskeleton in both sets of control mice upon renal injury, whereas the reconstituted mice had better preservation of the renal tubule actin cytoskeleton, which co-localized with the human-A(1)ARs. Consistent with reduced renal injury, there was a significant increase in heat shock protein-27 expression, also co-localizing with the preserved F-actin cytoskeleton. Our findings suggest that selective expression of cytoprotective A(1)ARs in the kidney can attenuate renal injury.
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Kidney international · Mar 2009
Interstitial tonicity controls TonEBP expression in the renal medulla.
Cells in the hyperosmotic kidney medulla, express a transcriptional activator termed tonicity responsive enhancer binding protein (TonEBP). Genes targeted by TonEBP protect kidney cells from the deleterious effects of hyperosmolality by inducing the expression of organic osmolytes and molecular chaperones, and other genes that mediate urine concentration such as aquaporin-2 and urea transporters. We tested here the effect of hypertonicity and hyperosmotic salt in the renal medullary interstitium on the expression TonEBP. ⋯ Here, TonEBP expression was blunted in the outer and inner medulla which was due, in part, to decreased mRNA abundance. As expected, the expression of TonEBP target genes in the renal medulla also decreased in response to furosemide. Hence TonEBP expression in the renal medulla is stimulated by interstitial hypertonicity.