Acute kidney injury in the intensive care unit is a clinically relevant problem requiring awareness and expertise among physicians from a wide variety of fields. Although many questions remain controversial and without definitive answers, a periodic update of this rapidly evolving field provides a framework for understanding and managing acute kidney injury in the intensive care unit.

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IntroductionInterleukin-6 (IL-6) is a proinflammatory cytokine that increases early in the serum of patients with acute kidney injury (AKI). The aim of this study was to determine whether urine IL-6 is an early biomarker of AKI and determine the source of urine IL-6. Numerous proteins, including cytokines, are filtered by the glomerulus and then endocytosed and metabolized by the proximal tubule. Since proximal tubule injury is a hallmark of AKI, we hypothesized that urine IL-6 would increase in AKI due to impaired proximal tubule metabolism of filtered IL-6.MethodsUrine was collected in 25 consecutive pediatric patients undergoing cardiac bypass surgery (CPB). AKI was defined as a 50% increase in serum creatinine at 24 hours (RIFLE (Risk, Injury, Failure, Loss, End stage), R). Mouse models of AKI and freshly isolated proximal tubules were also studied.ResultsUrine IL-6 increased at six hours in patients with AKI versus no AKI (X2 = 8.1750; P < 0.0042). Urine IL-6 > 75 pg/mg identified AKI with a sensitivity of 88%. To assess whether increased urine IL-6 occurs in functional versus structural renal failure, mouse models of pre-renal azotemia after furosemide injection (no tubular injury), ischemic AKI (tubular injury) and cisplatin AKI (tubular injury) were studied. Urine IL-6 did not significantly increase in pre-renal azotemia but did increase in ischemic and cisplatin AKI. To determine if circulating IL-6 appears in the urine in AKI, recombinant human (h)IL-6 was injected intravenously and urine collected for one hour; urine hIL-6 increased in ischemic AKI, but not pre-renal azotemia. To determine the effect of AKI on circulating IL-6, serum hIL-6 was determined one hour post-intravenous injection and was increased in ischemic AKI, but not pre-renal azotemia. To directly examine IL-6 metabolism, hIL-6 was added to the media of normal and hypoxic isolated proximal tubules; hIL-6 was reduced in the media of normal versus injured hypoxic proximal tubules.ConclusionsUrine IL-6 increases early in patients with AKI. Animal studies demonstrate that failure of proximal tubule metabolism of IL-6 results in increased serum and urine IL-6. Impaired IL-6 metabolism leading to increased serum IL-6 may contribute to the deleterious systemic effects and increased mortality associated with AKI.

Background/aims: To compare outcomes of critically ill patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) versus those with pre-existing end-stage renal disease (ESRD) requiring CRRT to identify factors that contribute to the increased mortality seen in AKI patients. Methods: Retrospective cohort of 257 intensive care unit (ICU) patients who received CRRT. AKI is defined as requiring CRRT with an admission serum creatinine ≤1 mg/dL; ESRD is defined as chronic dialysis dependence. Primary outcome was hospital mortality. Multivariate logistic regression was performed to determine the impact of APACHE II score, intubation, vasopressors, infection, diabetes, hypertension, gender, and race on mortality. Results: Of 257 patients requiring CRRT, 28 had ESRD and 108 had AKI. Hospital mortality was higher in patients with AKI versus ESRD (69% vs. 39%, p = 0.0032). Severity of illness using APACHE II was similar in AKI and ESRD. Patients with AKI were more likely to require mechanical ventilation (89% vs. 57%, p = 0.0003). After multivariate analysis, the requirement for mechanical ventilation was the single factor associated with increased hospital mortality [odds ratio (OR): 3.1]. Conclusions: In ICU patients requiring CRRT, patients with AKI have a higher mortality than patients with ESRD due to an increased need for mechanical ventilation.