LOW-DOSE DEXAMETHASONE-SUPPLEMENTED FLUID RESUSCITATION REVERSES ENDOTOXIN-INDUCED ACUTE RENAL FAILURE AND PREVENTS CORTICAL MICROVASCULAR HYPOXIA

Tanja Johannes, Bert Mik, K Klingel, HJ Dieterich, KE Unertl, Can Ince

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Abstract

There is growing evidence that impairment in intrarenal oxygenation and hypoxic injury might contribute to the pathogenesis of :septic renal failure. An important molecule known to act on the renal microvascular tone and therefore consequently being involved in the regulation of intrarenal oxygen supply is NO. The main production of NO under septic conditions derives from iNOS, an enzyme that can be blocked by dexamethasone (DEX). In an animal model of endotoxin-induced renal failure, we tested the hypothesis that inhibition of NOS by low-dose DEX would improve an impaired intrarenal oxygenation and kidney function. Twenty-two male Wistar rats received a 30-min intravenous infusion of LPS (2.5 mg/kg) and consecutively developed endotoxemic shock. Two hours later, in 12 animals, fluid resuscitation was initiated. Six rats did not receive resuscitation; four animals served as time control. In addition to the fluid, six animals received a bolus of low-dose DEX (0.1 mg/kg). In these animals, the renal iNOS mRNA expression was significantly :suppressed 3 h later. Dexamethasone prevented the appearance of cortical microcirculatory hypoxic areas, improved renal oxygen delivery, and significantly restored oxygen consumption. Besides a significant increase in MAP and renal blood flow, DEX restored kidney function and tubular sodium reabsorption to baseline values. In conclusion, treatment with low-dose DEX in addition to fluid resuscitation reversed endotoxin-induced renal failure associated by an improvement in intrarenal microvascular oxygenation. Therefore, low-dose DEX might have potential application in the prevention of septic acute renal failure.
Original languageUndefined/Unknown
Pages (from-to)521-528
Number of pages8
JournalShock
Volume31
Issue number5
DOIs
Publication statusPublished - 2009

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