Diagnosis and treatment of acute tubular necrosis.

BACKGROUND: Acute tubular necrosis (ATN) is common in hospitalized patients, particularly in the intensive care unit. Over the past four decades, the mortality rate from ATN has remained at 50% to 80%. PURPOSE: To review recent studies of diagnosis and treatment strategies for ATN. DATA SOURCES: MEDLINE search for all clinical studies of therapies for ATN, supplemented by a review of the references of the identified articles. STUDY SELECTION: Prospective studies and major retrospective studies evaluating therapies for ATN. DATA EXTRACTION: Data on the study sample, interventions performed, results, side effects, and duration of follow-up. DATA SYNTHESIS: Early diagnosis of ATN by exclusion of prerenal and postrenal causes of acute renal failure, examination of urinary sediment, and analysis of urine measures (for example, fractional excretion of sodium in the absence of diuretics) can allow the early involvement of nephrologists and improve survival. Enteral rather than parenteral hyperalimentation in severely malnourished patients may improve survival. Sepsis causes 30% to 70% of deaths in patients with ATN; therefore, avoidance of intravenous lines, bladder catheters, and respirators is recommended. Because septic patients are vasodilated, large volumes of administered fluid accumulate in the lung interstitium of these patients. This condition necessitates ventilatory support, which when prolonged leads to acute respiratory distress syndrome, multiorgan failure, and increased mortality. More aggressive dialysis (for example, given daily) with biocompatible membranes may improve survival in some patients with acute renal failure. CONCLUSIONS: New information about the importance of early diagnosis and supportive care for patients with ATN has emerged. However, randomized trials of these interventions are needed to test their effect on the morbidity and mortality of ATN.

Desensitization of soluble guanylate cyclase in renal cortex during endotoxemia in mice.

Acute endotoxemic renal failure involves renal vasoconstriction, which presumably occurs despite increased nitric oxide (NO) generation by inducible NO synthase in the kidney. The present study examined the hypothesis that the renal vasoconstriction during endotoxemia occurs in part because of desensitization of soluble guanylate cyclase (sGC). Endotoxic shock was induced in male B6/129F2/J mice by an intraperitoneal injection of Escherichia coli lipopolysaccharide. The endotoxemia resulted in shock and renal failure as evidenced by a decrease in mean arterial pressure and an increase in serum creatinine and urea nitrogen. Serum NO increased in a time-dependent manner, reaching the highest levels at 24 h, in parallel with induction of inducible NO synthase protein in the renal cortex. In renal cortical slices obtained from endotoxemic mice, cyclic guanosine monophosphate (cGMP) increased significantly at 6 h and 15 h as compared with control but normalized at 24 h after injection of lipopolysaccharide. Incubation of renal cortical slices in the presence of a phosphodiesterase inhibitor isobutylmethylxantine did not alter the pattern of changes in cGMP. Incubation of renal cortical slices with 2 mM sodium nitroprusside resulted in a similar accumulation of cGMP in slices taken from control and endotoxemic mice at 6 h and 15 h. However, in slices from 24-h endotoxemic mice, accumulation of cGMP in response to sodium nitroprusside was significantly lower. This lower stimulability of sGC was not paralleled by a decrease in its abundance in renal cortex on immunoblot. Taken together, these results demonstrate a desensitization of sGC in renal cortex during endotoxemia, which may contribute to the associated renal vasoconstriction.