Sepsis and the kidney: New developments in pathogenesis and treatment

Abstract

Sepsis is a common and important cause of mortality in critically ill patients. Acute kidney injury (AKI) is one of the most important factors determining morbidity and mortality in this clinical picture. Recent studies have indicated that the pathogenetic mechanism in septic acute kidney injury (AKI) is totally different from that in non-septic AKI. Our understanding of sepsis-associated AKI pathophysiology is shifting from renal vasoconstriction, ischemia, and acute tubular necrosis to that of heterogeneous vasodilation, hyperemia, and acute tubular apoptosis. Apoptosis is especially gradually gaining importance in the development of renal injury. In recently published studies, the frequency of renal tubular apoptosis on biopsies of septic patients has been pointed out. Apoptosis can be triggered by ischemia, exogenous toxins or endogenous mediators. In animal models, hyperglycemia, which is common in critically ill patients, has been shown to cause apoptosis in renal tubule cells. In the light of recent findings, new treatment options have emerged. Treatment of hyperglycemia has a different significance, since besides anti-inflammatory effect it has a protective role on the kidney. Hemofiltration methods cleaning toxic mediators from the circulation should be applied in the early stages. Ghrelin that inhibits pro-inflammatory cytokines, caspase inhibitors that block the apoptotic pathway, and nitric oxide synthase inhibitors are currently under study. Regarding pathogenesis, rates of morbidity and mortality are aimed to be reduced through the new agents of therapy that are being studied.