Clinical review: Optimal dose of continuous renal replacement therapy in acute kidney injury

Abstract

Continuous renal replacement therapy (CRRT) is the preferred treatment for acute kidney injury in intensive care units (ICUs) throughout much of the world. Despite the widespread use of CRRT, controversy and center-specific practice variation in the clinical application of CRRT continue. In particular, whereas two single-center studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with acute kidney injury in the ICU, other studies have been inconsistent in their results. Now, however, two large multi-center randomized controlled trials - the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study - have provided level 1 evidence that effluent flow rates above 25 mL/kg per hour do not improve outcomes in patients in the ICU. In this review, we discuss the concept of dose of CRRT, its relationship with clinical outcomes, and what target optimal dose of CRRT should be pursued in light of the high-quality evidence now available.

Figure 1

Possible relationship between delivered dose of continuous renal replacement therapy and survival, with results from the ATN and RENAL trials illustrated. ATN doses are corrected for pre-dilution. These studies indicate a plateau response at the dose ranges examined. To reproduce these results, clinicians will need to prescribe continuous renal replacement therapy doses above the lower target dose in the trial protocols (20 or 25 mL/kg per minute) as larger periods of filter downtime can be expected outside a clinical trial environment. Below this best-practice region, survival is likely to be dose-dependent; however, the exact nature of this relationship has not been formally determined. Doses above the best-practice region are unlikely to be beneficial to unselected patients and could potentially be harmful. ATN, Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network; RENAL, Randomized Evaluation of Normal versus Augmented Level. Adapted from Kellum and Ronco [18] 2010.