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

Abstract

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.

Current Approach to Successful Liberation from Renal Replacement Therapy in Critically Ill Patients with Severe Acute Kidney Injury: The Quest for Biomarkers Continues

“…No clinical guidelines currently provide clear recommendations on the optimal timing of liberation from acute RRT in AKI-D patients recovering renal function [ 16 , 17 ]. The uncertainty regarding a safe and successful liberation strategy from RRT results in heterogeneous care, which is not driven by the best evidence but by empiricism and local logistics.…”

“…By contrast, steady-state concentrations of this surrogate marker during continuous renal replacement therapy (CRRT) allow calculations of creatinine clearance at 2, 6 or 24 h. Generally, creatinine clearance values obtained from patients with AKI overestimate the true glomerular filtration rate due to tubular creatinine secretion. To achieve a more accurate creatinine clearance the kinetic estimated GFR has been used in small study populations [ 16 , 18 ].…”

“…Katulka et al conducted a systematic review and meta-analysis to identify predictors of successful liberation from acute RRT in critically ill patients with AKI D [ 16 ]. Twenty-three cohort studies (18 full-text articles, five conference abstracts and two case–control studies) fulfilled the inclusion criteria.…”

Strategies for Continuous Renal Replacement Therapy De-escalation

“…Novel renal biomarkers such as cystatin C, NGAL, IL-18, IL-6, serum osteopontin, have been studied albeit with limited consistency in their prediction; It is important to note that current data on biomarkers stems from small, isolated, observational studies, with significant heterogeneity in their definitions of successful discontinuation, weaning criteria, and timing of measurement of biomarkers, and threshold values. Cystatin C remains the most commonly studied biomarker and was found to be an independent positive predictor for weaning off CRRT (4,9). Limitations exist that may restrict cystatin C use in certain clinical situations such as with corticosteroid use, thyroid dysfunction, and underlying malignancy.…”

Whether the GFR measured by renal scintigraphy under non-steady state conditions for critically ill patients with AKI can be used as a predictive parameter for clinical events

“…We read with great attention and interest the paper by Katulka et al about the current evidence for clinical and biochemical parameters for predicting successful discontinuation of RRT [1]. We would like to add some comments in regard to their conclusion that multiple studies reported on the same parameter (urine output, diuretic test, CrCl, cystatin C, NGAL, eGFR, KeGFR), but an optimal threshold value was not determined due also to heterogeneity.…”