Assessment of plasma endostatin to predict acute kidney injury in critically ill patients.

BACKGROUND: We evaluated whether plasma endostatin predicts acute kidney injury (AKI), need for renal replacement therapy (RRT), or death. METHODS: Prospective, observational, multicenter study from 1 September 2011 to 1 February 2012 with data from 17 intensive care units (ICUs) in Finland. RESULTS: A total of 1112 patients were analyzed. We measured plasma endostatin within 2 h of ICU admission. Early AKI (KDIGO stage within 12 h of ICU admission) was found in 20% of the cohort, and 18% developed late AKI (KDIGO criteria > 12 h from ICU admission). Median (IQR) admission endostatin was higher in the early AKI group, 29 (19.1, 41.9) ng/ml as compared to 22.4 (16.1, 30.1) ng/ml for the late AKI group, and 18 (14.0, 23.6) ng/ml for non-AKI patients (P < 0.001). Endostatin level increased with increasing KDIGO stage. Significantly higher endostatin levels were found in patients with sepsis as compared to those without. Predictive properties for AKI, RRT, and mortality were low with corresponding areas under the receiver operating characteristic curve (AUC) of 0.62, 0.67, and 0.59. Sensitivity analyses among patients with chronic kidney disease or sepsis did not improve the predictive ability of endostatin. Adding endostatin to a clinical AKI prediction model (illness severity score, urine output, and age) insignificantly changed the AUC from 0.67 to 0.70 (P = 0.14). CONCLUSIONS: Endostatin increases with AKI severity but has limited value as a predictor of AKI, RRT and 90-day mortality in patients admitted to ICU. Moreover, endostatin does not improve AKI risk prediction when added to a clinical risk model.

Association of plasma chloride values with acute kidney injury in the critically ill - a prospective observational study.

BACKGROUND: Chloride-rich fluids have been found to associate with an increased risk for acute kidney injury (AKI) among intensive care unit (ICU) patients. Studies evaluating the association of plasma chloride (Cl) with the development of AKI are few. We hypothesized that higher plasma Cl is associated with an increased risk for the development of AKI. METHODS: In this sub-study of the prospective FINNAKI study, we analyzed Cl values measured during ICU stay in two ICUs at a tertiary center including 445 patients. We calculated time-weighted mean values within the first 24 h in ICU for plasma Cl (ClTWM 24 ). We analyzed the association of ClTWM 24 primarily with the development of AKI, and secondarily with 90-day mortality. RESULTS: Based on the first measured Cl value, 350 of 445 patients [78.7 (95 CI, 74.8-82.5)] had hyperchloremia (P-Cl > 106 mmol/l) and 48 [10.8 (95 CI, 7.9-13.7)] severe hyperchloremia (P-Cl > 114 mmol/l). Altogether 217 of 445 [48.8% (95% CI 44.2-53.4%)] patients developed AKI. Of these 217, AKI was diagnosed in 62 (28.6%) after 24 h from ICU admission and were included in the analysis regarding development of AKI. ClTWM 24 was associated with an increased risk for the development of AKI (OR1.099; 1.003-1.205) after multivariable adjustments. According to ClTWM 24 , no difference in 90-day mortality between severely hyperchloremic patients and others existed. CONCLUSIONS: More than three of four critically ill patients had hyperchloremia and 1 of 10 had its severe form. Higher time-weighted mean chloride was independently associated with an increased risk for AKI.

Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients.

BACKGROUND: Interleukin-18 (IL-18) is a pro-inflammatory protein, which mediates ischaemic tubular injury, and has been suggested to be a sensitive and specific biomarker for acute kidney injury (AKI). The predictive value of IL-18 in the diagnosis, evolution, and outcome of AKI in critically ill patients is still unclear. METHODS: We measured urine IL-18 from critically ill patients at intensive care unit (ICU) admission and 24 h. We evaluated the association of IL-18 with developing new AKI, renal replacement therapy (RRT), and 90-day mortality. We calculated areas under receiver operating characteristics curves (AUCs), best cut-off values, and positive likelihood ratios (LR+) for IL-18 concerning these endpoints. Additionally, we compared the predictive value of IL-18 at ICU admission to that of urine neutrophil gelatinase-associated lipocalin (NGAL). RESULTS: In this study population of 1439 patients the highest urine IL-18 during the first 24 h in the ICU associated with the development of AKI with an AUC [95% confidence interval (CI)] of 0.586 (0.546-0.627) and with the development of Stage 3 AKI with an AUC (95% CI) of 0.667 (0.591-0.774). IL-18 predicted the initiation of RRT with an AUC (95% CI) of 0.655 (0.572-0.739), and 90-day mortality with an AUC (95% CI) of 0.536 (0.497-0.574). CONCLUSIONS: IL-18 had poor-to-moderate ability to predict AKI, RRT, or 90-day mortality in this large cohort of critically ill patients. Thus, it should be used with caution for diagnostic or predictive purposes in the critically ill.

Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units.

BACKGROUND: Severe sepsis is one of the leading causes of acute kidney injury (AKI). Patients with sepsis-associated AKI demonstrate high-hospital mortality. We evaluated the incidence of severe sepsis-associated AKI and its association with outcome in intensive care units (ICUs) in Finland. METHODS: This was a predetermined sub-study of the prospective, observational, multicentre FINNAKI study conducted in 17 ICUs during 1 September 2011 and 1 February 2012. All emergency ICU admissions and elective admissions exceeding 24 hours in the ICU were screened for presence of severe sepsis and AKI up to 5 days in ICU. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria and severe sepsis according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. RESULTS: Of the 2901 included patients, severe sepsis was diagnosed in 918 (31.6%, 95% confidence interval [CI] 29.9-33.4%) patients. Of these 918 patients, 488 (53.2% [95% CI 49.9-56.5%]) had AKI. The 90-day mortality rate was 38.1% (95% CI 33.7-42.5%) for severe sepsis patients with AKI and 24.7% (95% CI 20.5-28.8%) for those without AKI. After adjusting for covariates, KDIGO stage 3 AKI was associated with an increased risk for 90-day mortality with an adjusted odds ratio (OR) of 1.94 (95% CI 1.28-2.94), but stages 1 and 2 were not. CONCLUSIONS: More than half of the patients with severe sepsis had AKI according to the KDIGO classification, and AKI stage 3 was independently associated with 90-day mortality.

Association of ICU size and annual case volume of renal replacement therapy patients with mortality.

BACKGROUND: We aimed to reveal whether the size of an intensive care unit (ICU) or its annual case volume of patients treated with renal replacement therapy (RRT) for acute kidney injury (AKI) is associated with hospital mortality. METHODS: This was a retrospective cohort study in the Finnish Intensive Care Consortium (FICC) database in 2007-2008. We divided the 23 FICC-member ICUs first into small or large according to ICU size, and second into low, medium, or high-volume tertiles according to annual case volume of patients with RRT. We compared crude hospital mortality, Simplified Acute Physiology Score (SAPS) II-, and case-mix-adjusted hospital mortality in small vs. large ICUs and in low- or medium-volume vs. high-volume ICUs. RESULTS: The median (interquartile range) annual case volume of patients with RRT for AKI per one ICU was 25 (19-45). Patients in small or low-volume ICUs were older and less severely ill. Crude and SAPS II -adjusted hospital mortality rates were significantly higher in small ICUs but not significantly different in case volume tertiles. After adjusting for age, severity of illness, intensity of care, propensity to receive RRT, and day of RRT initiation, treatment in low or medium volume ICUs was associated with an increased risk for hospital mortality. CONCLUSIONS: Crude and adjusted hospital mortality rates of patients treated with RRT for AKI were higher in small ICUs. Patients treated in high-volume ICUs had a decreased adjusted risk for hospital mortality compared to those in low-or medium volume ICUs.