A study appearing today in the New England Journal of Medicine adds to the growing body of evidence supporting continuous renal replacement therapy (CRRT) as the therapy of choice for treatment of acute kidney injury (AKI) patients in the intensive care unit (ICU).
The Randomized Evaluation of Normal versus Augmented Level of renal replacement (RENAL) Study was a multi-center, randomized controlled trial with 1,508 critically ill AKI patients in Australia and New Zealand. CRRT was the initial therapy in all patients, who were randomly assigned to a higher-intensity group (CRRT dose of 40 mL/kg/hr) or a lower-intensity group (CRRT dose of 25 mL/kg/hr). CRRT was the initial dialysis modality used for all AKI patients in RENAL and used nearly exclusively while patients remained in the ICU. The study did not show meaningful differences between the higher-intensity and lower-intensity CRRT groups, either with respect to mortality or renal recovery.
"The RENAL Study improves our understanding of dose and outcomes," says Dr. Rinaldo Bellomo, Principal Investigator for the study. "It provides important findings on renal recovery and mortality."
Excellent patient outcomes achieved in RENAL
In the RENAL Study, 90-day all-cause mortality was only 45%, which represents a major improvement in AKI survival relative to prior studies involving patients with similar illness severity. As noted in the RENAL publication, AKI requiring renal replacement therapy in the ICU has historically been associated with a mortality rate of 60%.
Both the RENAL and the Acute Renal Failure Trial Network (ATN) Studies provide new evidence suggesting the appropriate use of CRRT improves AKI patient outcomes. The ATN Study was a large, randomized controlled clinical trial sponsored by the U.S. Department of Veterans Affairs and the National Institutes of Health.
While CRRT was essentially the only therapy used in the RENAL Study, it was also the modality applied almost exclusively to hemodynamically unstable patients in the ATN Study. Similar to the RENAL Study, mortality outcomes were very good in the ATN Study. The widespread use of CRRT in the two trials, at least in the most critically ill patients, was likely a major factor contributing to the improved survival.
In RENAL, 94% of surviving patients recovered renal function by 90 days, despite the inclusion of a large number of patients with significant pre-existing chronic kidney disease (CKD). These results corroborate several prior studies that have suggested a benefit for CRRT over intermittent hemodialysis with respect to renal recovery. The findings are noteworthy because recent data clearly indicate AKI can cause or contribute to the development of end-stage renal disease, especially in patients with CKD.
Early initiation may have contributed to excellent outcomes
After admission to the ICU, CRRT was initiated on average after only about two days (mean, 50 hours). This timing of treatment initiation is earlier than that typically applied in previous studies and in general clinical practice. Therefore, in addition to the predominant use of CRRT, early CRRT initiation may have contributed to the excellent outcomes achieved in RENAL.
Study emphasizes importance of assessing delivery of prescribed CRRT dose
While RENAL and ATN provide clinicians with important new understanding of the value of CRRT, they do not provide definitive information about the optimal CRRT dose with respect to patient outcomes. The data suggest a CRRT dose of 25 mL/kg/hr is a reasonable target. In addition, consistent with standard practice in chronic dialysis, the results of these two trials suggest prescribed dose should exceed the delivered dose target to compensate for shortfalls in treatment delivery.
RENAL Study employs Gambro technology
In RENAL, the Gambro AN69 filter and Gambro bicarbonate-based replacement fluid and dialysate were used uniformly across the study, confirming the clinical benefits of these widely used CRRT products. The investigators' choice to exclusively use Gambro's filter and fluid products confirms clinicians' recognition of the clinical benefits of Gambro's CRRT products.