Biomarkers upon discontinuation of renal replacement therapy predict 60‐day survival and renal recovery in critically ill patients with acute kidney injury

Abstract

Introduction: There is no consensus on the specific indications for weaning critically ill patients with acute kidney injury (AKI) off renal replacement therapy (RRT). This study aimed to explore the prognostic value of several biomarkers measured upon discontinuation of RRT for their value in predicting 60-day survival and renal recovery in an effort to add knowledge to the decision-making process regarding RRT withdrawal. Methods:We prospectively enrolled 102 patients with AKI who required RRT from the intensive care unit. Serum osteopontin (sOPN), serum interleukin 6 (sIL-6), serum cystatin C (sCysC), sIL-18, serum neutrophil gelatinase-associated lipocalin and urinary IL-18 and urinary neutrophil gelatinase-associated lipocalin were measured upon discontinuation of RRT. Patients were followed up at 60 days for survival and renal recovery. Findings:Patients who survived showed lower levels of all serum and urinary biomarkers. Serum OPN (OR 1.029, 95% CI 1.013-1.047, P 5 0.001), diabetes (OR 23.157, 95% CI 4.507-118.981, P < 0.001) and APACHE II score (OR 1.308, 95% CI 1.121-1.527, P 5 0.001) were independent predictors of 60-day mortality. Patients whose sOPN values fell within the highest and middle tertiles showed 5.25-and 2.31-fold increased risks of mortality, respectively, compared with that of patients in the lowest tertile. The addition of sOPN to the clinical model resulted in significant net reclassification improvement of 0.453 (P 5 0.026) and an integrated discriminative index of 0.155 (P 5 0.032). Lower levels of sOPN and sIL-6 were associated with greater odds of 60-day survival (AUC 0.812 and 0.741). The AUC value for predicting survival reached its highest level when all biomarkers were combined with urine output (UO) and urinary and serum creatinine upon discontinuation of RRT (0.882). Lower sCysC performed as well as higher UO in predicting 60-day renal recovery with the greatest AUC of 0.743.Discussion: Upon discontinuation of RRT, serum and urinary biomarkers, particularly sOPN, may predict 60-day survival and renal recovery in critically ill patients with AKI. The serum levels of OPN, IL-6 and CysC may be useful when considering withdrawal of RRT on the basis of conventional indicators.

A Prospective Observational Study on the Predictive Value of Serum Cystatin C for Successful Weaning from Continuous Renal Replacement Therapy

“…Similarly, a recent study also found that serum CysC, measured when RRT was discontinued, showed the largest AUC value for predicting 60-day renal recovery. In this study, recovery was defined as a serum creatinine level not exceeding 0.5 mg/dL above the baseline value, in patients with AKI who required RRT in the ICU [10]. These results could be supported by the evidence that levels of CysC are less likely to be influenced by continuous venovenous hemodiafiltration or hemofiltration, compared with serum NGAL or creatinine [21][22][23].…”

“…However, urine output at the time of cessation was reported as the most important predictor of the successful weaning of RRT [7][8][9][10]26], and many studies adapted the criteria for discontinue RRT based on the urine output exceeded 400−500ml/day [4,5,27]. Uchino et al found that a urine output of > 400 ml/day, without diuretics at CRRT cessation, had the greatest AUC value of 0.845, but diuretics negatively affected the predictive ability of urine output [8].…”

“…However, compared to the evidence on the timing of RRT initiation, there is a lack of data on the optimal timing for discontinuing RRT. Although a few observational studies found that urine output, at the time of continuous RRT (CRRT) cessation, was predictive for restarting RRT, the predictive ability of urine output was negatively modified by diuretics that were used to increase urine output and facilitate CRRT cessation [7][8][9][10]. Therefore, KDIGO guidelines have recommended further research programs to determine the clinical parameters or biomarkers that indicate renal recovery and to predict successful discontinuation of RRT in AKI patients [11].…”

“…Moreover, neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be an early biomarker for predicting AKI before serum creatinine increases [14]. However, to date, data is lacking regarding the biomarkers or clinical factors that could guide clinical decisions on the optimal time to discontinue CRRT or to predict the successful weaning from CRRT in AKI patients [2,10,15]. The aim of our study was to identify the level of serum CysC or serum NGAL, at the time of CRRT cessation, that is associated with successful weaning from CRRT.…”

The Effect of Serum Neutrophil Gelatinase-Associated Lipocalin on the Discontinuation of Continuous Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury

“…The predictive effect of NGAL was not further analyzed in the different groups. Additionally, another study assessed the prognostic value of several biomarkers measured upon the discontinuation of RRT for their value in predicting 60-day survival and renal recovery; the study reported that serum CysC (AUROC 0.743, p = 0.002) and urine output (AUROC 0.743, p = 0.002) were better predictors of 60-day renal recovery than serum creatinine (AUROC 0.691, p = 0.015) and NGAL (AUROC 0.661, p = 0.04) [23]. Renal recovery was defined as a serum creatinine level no higher than 0.5 mg/dL above the baseline value.…”