Sepsis and Acute Kidney Injury Are Bidirectional

Abstract

Sepsis is the most common cause of acute kidney injury (AKI). There has been a growing body of evidence demonstrating the association between worsening of kidney function during sepsis and the risk of short- and long-term mortality. AKI in sepsis is associated with poor outcome and independently predicts increased mortality. Sepsis-associated AKI may therefore serve as a biomarker of adverse physiological events that portends worse outcome. Conversely, the important role of sepsis among intensive care unit patients with nonseptic AKI is increasingly being recognized. Indeed, sepsis represents a significant contributing factor to the overall mortality and incomplete recovery of kidney function in subjects who developed nonseptic AKI. Because AKI portends such an ominous prognosis in sepsis and vice versa, there has been a surge of interest in elucidating mechanisms underlying the complex and bidirectional nature of the interconnections between AKI, sepsis and multiorgan dysfunction. Accumulating data indicate that AKI can trigger several immune, metabolic and humoral pathways, thus potentially contributing to distant organ dysfunction and overall morbidity and mortality. The expanding population of patients with sepsis and AKI, and the associated excess mortality provide a strong basis for further research aimed at addressing more rigorously all potentially modifiable factors to reduce this burden to patients and health care systems. Better insights into bidirectional and synergistic pathways linking sepsis and AKI might open the window for new therapeutic approaches that interrupt this vicious circle. Here, we discuss the rationale for and the current understanding of the bidirectional relationship between AKI and sepsis.

Association Between Acute Kidney Injury and In-Hospital Mortality in Patients Undergoing Percutaneous Coronary Interventions

“…First, AKI is frequently complicated by altered immune function, increased propensity to infection, bleeding, and thrombosis. 25,26 Second, AKI can result in acute volume overload, acidemia, and hyperkalemia contributing to increased cardiac stress and risk of arrhythmias. 27 Third, crosstalk between the kidney and other organs involving inflammatory and proapoptotic pathways may result in multiorgan failure eventually causing death.…”

l-Arginine attenuates the ethylene glycol induced urolithiasis in ininephrectomized hypertensive rats: role of KIM-1, NGAL, and NOs

“…89,90 In AKI, the mortality rates remained high due to paucity in the sensitive and specific biomarkers of renal cell injury. 89,91 However, recently developed techniques have identified the two sensitive and specific biomarkers for early AKI, namely, kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). 92,93 It has been reported that the sensitivity for NGAL to predict AKI is 0.815.…”

Paclitaxel Ameliorates Lipopolysaccharide-Induced Kidney Injury by Binding Myeloid Differentiation Protein-2 to Block Toll-Like Receptor 4–Mediated Nuclear Factor-κB Activation and Cytokine Production

“…In kidneys, sepsis induces acute injury, tissue damage, and decrease of renal function, diminishing the efficacy of fluid supplementation and other therapeutics (Matejovic et al, 2011;Zarjou and Agarwal, 2011;Mayeux and MacMillan-Crow, 2012). Development of new drugs to treat septic acute kidney injury (AKI) therefore has a great potential to reduce mortality and morbidity in patients (Bagshaw et al, 2009;Zarjou and Agarwal, 2011).…”