Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function

Abstract

To better understand the diagnostic and predictive performance of urinary biomarkers of kidney injury, we evaluated γ-glutamyltranspeptidase (GGT), alkaline phosphatase (AP), neutrophil-gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in a prospective observational study of 529 patients in 2 general intensive care units (ICUs). Comparisons were made using the area under the receiver operator characteristic curve (AUC) for diagnosis or prediction of acute kidney injury (AKI), dialysis, or death, and reassessed after patient stratification by baseline renal function (estimated glomerular filtration rate, eGFR) and time after renal insult. On ICU entry, no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI. Several biomarkers (NGAL, CysC, and IL-18) predicted dialysis (AUC over 0.7), and all except KIM-1 predicted death at 7 days (AUC between 0.61 and 0.69). Performance was improved by stratification for eGFR or time or both. With eGFR <60ml/min, CysC and KIM-1 had AUCs of 0.69 and 0.73, respectively, within 6 h of injury, and between 12 and 36 h, CysC (0.88), NGAL (0.85), and IL-18 (0.94) had utility. With eGFR >60 ml/min, GGT (0.73), CysC (0.68), and NGAL (0.68) had the highest AUCs within 6h of injury, and between 6 and 12 h, all AUCs except AP were between 0.68 and 0.78. Beyond 12 h, NGAL (0.71) and KIM-1 (0.66) performed best. Thus, the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI.

Risk of Poor Outcomes with Novel and Traditional Biomarkers at Clinical AKI Diagnosis

“…In a more recent report of urine biomarkers obtained during the EARLARF trial, in which no differences were seen (i.e., development of AKI in 48 hours, need for dialysis, or death in 7 days) between erythropoietin and placebo on admission to the ICU (31), five of the six biomarkers studied predicted death within 7 days with AUCs from 0.61 to 0.68 (32). Urine NGAL, IL-18, and cystatin C also predicted the need for dialysis with AUCs from 0.71 to 0.79.…”

The Use of Plasma and Urine Neutrophil Gelatinase Associated Lipocalin (NGAL) and Cystatin C in Early Diagnosis of Septic Acute Kidney Injury in Critically Ill Patients

“…It was shown previously in many clinical studies and has been accepted that NGAL and Cystatin C levels increase in different clinical settings leading to AKI development [10][11][12][13][14][15][16][17][18][19][20][21][22]. Since the aim of this study is to define the roles of Cystatin C and NGAL in predicting septic AKI development, the patients who had other risk factors, rather than sepsis, that would lead to AKI and increase the Cystatin C and NGAL levels (i.e., nonseptic-AKI patients) were excluded from the study.…”

“…They are investigated in different clinical settings including cardiac surgery [10], contrast agent use [11], critically ill patients [12][13][14][15][16][17][18][19][20][21] and in emergency department [22].…”

Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort

“…203 participants died of which 90 died of cardiovascular causes. Total mortality incidence rate (95% CI) was 50 (44-58) and cardiovascular mortality incidence rate 22 (18)(19)(20)(21)(22)(23)(24)(25)(26)(27) per 1000 person-years.…”

“…The remaining CysC is eliminated in the urine and urinary CysC (u-CysC) concentrations are thus normally very low [9][10][11]. Tubular dysfunction reduce the degradation leading to a subsequent increase in uCysC concentrations and several studies have suggested that u-CysC is a reliable biomarker of acute tubular damage [5,[12][13][14][15][16][17][18][19][20] and worse prognosis [16,19] in critically ill patients.…”