Optimal timing of initiation and discontinuation of continuous renal replacement therapy in intensive care unit: can we install novel biomarkers for the decision?

Abstract

Renal replacement therapy (RRT) is one of the key treatment modalities for critically ill patients in the intensive care unit (ICU). Recently, the results from several large randomized controlled trials on the optimal timing of RRT initiation became available. Most of these results showed no significant merit in early initiation of RRT when they defined “early” treatment depending on serum creatinine value and urine amount. However, there is less evidence on the optimal timing of discontinuing RRT. Each ICU physician has to decide when to stop RRT according to several indicators, including urine amount, other clinically available biomarkers, and overall patient status. In this narrative review, we summarized the previous studies on these topics. We also quoted the result of our recent multi-centered observational study on patients with continuous RRT in seven university-affiliated ICUs across Japan. This study validated three clinical biomarkers: urinary neutrophil gelatinase-associated lipocalin (NGAL), serum interleukin-6 (IL-6), and serum high mobility group box 1. Consequently, higher urinary NGAL and serum IL-6 levels at RRT initiation were significantly correlated with subsequent mortality. Meanwhile, lower urinary NGAL level at RRT discontinuation was significantly correlated with successful RRT discontinuation in the following seven days. Future larger studies should focus on implementing these biomarkers to decide when to start and stop RRT in ICU.