Atypical Sepsis-Associated Acute Kidney Injury

The overall incidence of acute kidney injury (AKI) in the USA is estimated to be about 7/1000 population [1]. Older adults and children are disproportionately affected in a bimodal distribution mirroring the incidence of sepsis [2], the leading cause of AKI [3–6]. Even mild forms of AKI are associated with increased risk of hospital mortality [6, 7], and AKI may result in chronic kidney disease and life-long morbidity, shortened survival and increased costs [8]. Moreover, severity of AKI varies by etiology and sepsis-associated AKI tends to be most severe. For example, KDIGO stage 3 occurs in 20% of patients with septic shock [9]. Once acquired, the consequences of AKI are also unequally distributed. Approximately one third of patients exhibit no reversal of renal dysfunction within the first few days of AKI. Roughly 25% will never recover, and experience a fivefold increase in mortality over the ensuing year [10]. Even among patients with sepsis-associated AKI, outcomes are heterogeneous and different mechanisms may be involved [11]—indeed, no fewer than six have been proposed [12]. Renal endothelial pathology is prevalent in experimental models of sepsis [12, 13]. Endothelial injury can reduce microcirculatory flow leading to perfusion abnormalities and interstitial infiltration of inflammatory cells [13]. However, the reasons some patients exhibit these pathologic features while others do not are obscure.