From Hemodynamics To Proteomics: Unraveling the Complexity of Acute Kidney Injury in Sepsis
Sepsis is a complex syndrome characterized by an uncontrolled and deregulated systemic inflammatory response to infection. This is mediated by a broad spectrum of endogenous mediators whose actions result in multiple organ dysfunction distant from the original focus of infection. The kidney is a common ‘victim organ’ of various insults in critically ill patients. Sepsis and septic shock are the dominant causes of acute kidney injury (AKI), accounting for nearly 50% of episodes of acute renal failure . The incidence of AKI in sepsis increases proportionally with the severity of sepsis, with AKI developing in 19% of patients with sepsis, 23% of those with severe sepsis, and 51% of patients with septic shock . The mortality of sepsis patients with co-existing acute renal failure reaches 70%, thereby outstripping that of patients with other causes of AKI . Interestingly, even relatively minor increments in serum creatinine levels coincide with markedly increased morbidity and mortality , highlighting the potentially important role of kidney dysfunction during the natural history of critical illness. However, the precise understanding of the multifactorial mechanisms of sepsis-induced AKI that would allow the development of new therapeutic strategies to prevent AKI or to hasten its recovery remains a mystery. Here, we review the most recent advances in the understanding of the molecular mechanisms and pathophysiology of sepsis-induced AKI, focusing on renal hemodynamic and microvascular changes and on the importance of a rapidly evolving proteomics approach to evaluating sepsis-induced kidney dysfunction.
KeywordsSeptic Shock Acute Renal Failure Acute Kidney Injury Renal Blood Flow Efferent Arteriole
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