Determining the optimal time for liberation from renal replacement therapy in critically ill patients: a systematic review and meta-analysis (DOnE RRT).

INTRODUCTION: Renal replacement therapy (RRT) is associated with high mortality and costs; however, no clinical guidelines currently provide specific recommendations for clinicians on when and how to stop RRT in recovering patients. Our objective was to systematically review the current evidence for clinical and biochemical parameters that can be used to predict successful discontinuation of RRT. METHODS: A systematic review and meta-analysis were performed with a peer-reviewed search strategy combining the themes of renal replacement therapy (IHD, CRRT, SLED), predictors of successful discontinuation or weaning (defined as an extended period of time free from further RRT), and patient outcomes. Major databases were searched and citations were screened using predefined criteria. Studied parameters were reported and, where possible, data was analyzed in the pooled analysis. RESULTS: Our search yielded 23 studies describing 16 variables for predicting the successful discontinuation of RRT. All studies were observational in nature. None were externally validated. Fourteen studies described conventional biochemical criteria used as surrogates of glomerular filtration rate (serum urea, serum creatinine, creatinine clearance, urine urea excretion, urine creatinine excretion). Thirteen studies described physiologic parameters such as urine output before and after cessation of RRT, and 13 studies reported on newer kidney biomarkers, such as serum cystatin C and serum neutrophil gelatinase-associated lipocalin (NGAL). Six studies reported sensitivity and specificity characteristics of multivariate models. Urine output prior to discontinuation of RRT was the most-studied variable, with nine studies reporting. Pooled analysis found a sensitivity of 66.2% (95% CI, 53.6-76.9%) and specificity of 73.6% (95% CI, 67.5-79.0%) for urine output to predict successful RRT discontinuation. Due to heterogeneity in the thresholds of urine output used across the studies, an optimal threshold value could not be determined. CONCLUSIONS: Numerous variables have been described to predict successful discontinuation of RRT; however, available studies are limited by study design, variable heterogeneity, and lack of prospective validation. Urine output prior to discontinuation of RRT was the most commonly described and robust predictor. Further research should focus on the determination and validation of urine output thresholds, and the evaluation of additional clinical and biochemical parameters in multivariate models to enhance predictive accuracy.

Determining the optimal time for liberation from renal replacement therapy in critically ill patients: protocol for a systematic review and meta-analysis (DOnE RRT).

INTRODUCTION: Renal replacement therapy (RRT) is a complex and expensive form of life-sustaining therapy, reserved for our most acutely ill patients. While a number of randomised trials have evaluated the optimal timing to start RRT among critically ill patients in the intensive care unit (ICU), there has been a paucity of trials providing guidance on when and under what circumstances to ideally liberate a patient from RRT. We are conducting a systematic review and meta-analysis to identify clinical and biochemical markers that predict kidney recovery and successful liberation from acute RRT among critically ill patients with acute kidney injury. METHODS AND ANALYSIS: Our comprehensive search strategy was developed in consultation with a research librarian and independently peer-reviewed by a second librarian. We will search electronic databases: Ovid Medline, Ovid Embase and Wiley Cochrane Library. Selected grey literature sources will also be searched. Our search strategies will focus on concepts related to RRT (ie, intermittent haemodialysis, slow low-efficiency dialysis, continuous renal replacement therapy), intensive care (ie, involving any ICU setting) and discontinuation of therapy (ie, either clinical, physiological and biochemical parameters of weaning acute RRT) from 1990 to October 10, 2017. Citation screening, selection, quality assessment and data abstraction will be performed in duplicate. Studies will, where possible, be pooled in statistical meta-analysis. When deemed sufficiently clinically homogenous, and we have four or more studies reporting, sensitivities and specificities will be pooled simultaneously using a hierarchical summary receiver operator characteristic curve and bivariate analysis. ETHICS AND DISSEMINATION: Our systematic review will synthesise the literature on clinical and biochemical markers that predict liberation from RRT. Research ethics approval is not required. TRIAL REGISTRATION NUMBER: CRD42018074615.