Researchers at the Mayo Clinic, in Rochester, Minnesota, report what they say is the first study to examine correlates of successful liberation from continuous renal replacement therapy (CRRT) in a large cohort of patients who started on dialysis with CRRT in the intensive care unit (ICU) at Mayo because of incident acute kidney injury (AKI).
Several prior reports have prospectively assessed, in randomized studies, the optimal approach to starting renal replacement therapy in patients with AKI while in ICU. However, scant evidence exists on when and how to best stop CRRT without the need to subsequently resume it, or a different form of dialysis, what’s known as CRRT “liberation.”
In this new, retrospective, single-center, observational study, the Mayo investigators found a “high” failure rate and “poor” survival and kidney-related outcomes among patients with AKI who underwent CRRT liberation in ICU, the team writes in their recent report, published in Mayo Clinic Proceedings.
However, they did identify variables that can be used to predict better outcomes when planning to attempt CRRT liberation, such as patients who were less sick on ICU admission, those with a shorter duration of CRRT, and patients with higher urinary output just before the liberation attempt.
Their new findings “underscore the need for additional data and consensus guidelines to support the clinical practices of CRRT liberation,” they add. “There is no consensus on how to properly liberate patients from CRRT,” a decision that clinicians currently make based on personal experience resulting in practice variability.
Acute kidney injury is a common condition that patients admitted to ICU can develop and is associated with high morbidity and mortality.
The Importance of CRRT Liberation
“We used one of the largest CRRT datasets in North America to point out that liberation from dialysis is as important as the initiation of CRRT,” explained Kianoush B. Kashani, MD, senior author of the report and professor of medicine at the Mayo Clinic.
“The purpose of our research was to highlight the importance of the liberation phase, as its association with mortality is tremendous,” he said in an interview.
The analysis showed that durable CRRT liberation was “marginally” associated with a relative 29% lower rate of major adverse kidney events during 90 days after the start of CRRT compared with patients who had to restart CRRT or another dialysis method following initial discontinuation, although the difference was not significant after adjustment for potential confounders (P = .08).
The researchers also found no significant difference in the cumulative probability of death during the 90-day follow-up between successfully liberated patients and those who had to restart dialysis.
However, successful CRRT liberation did significantly and independently link with an 81% relative increase in the rate of kidney recovery after 90 days compared with those who had to resume dialysis.
Deciding When to Stop
Based on findings from recent reports involving several thousand patients — most recently the STARRT-AKI trial with more than 2900 patients, as reported by Medscape Medical News — “the question of when to start CRRT is settled.”
“What remains unknown is how do you decide when to stop? How do you liberate patients from CRRT? This is the next frontier for research to develop guidelines,” commented Oleksa Rewa, MD, a critical care medicine physician at the University of Alberta in Edmonton, Canada, who was not involved with the Mayo study.
“Research that focuses on promoting recovery is important. We hope our study is the beginning of many investigations on this critical topic,” said Kashani, who specializes in nephrology and critical care medicine.
Updated guidelines on managing patients with AKI are now in process, an effort organized by the Kidney Disease: Improving Global Outcomes (KDIGO) program, with a goal for their release by 2024, Kashani said in an interview.
The study run by Kashani and colleagues tapped into data from nearly 117,000 adults admitted to Mayo’s ICU over more than 11 years starting in 2007. They focused on patients with AKI who began on CRRT following ICU admission. This included 470 patients who died within the first 72 hours following attempted CRRT liberation, 437 who attempted liberation but then had to either restart CRRT or start intermittent hemodialysis, and 228 patients (20% of the cohort that attempted liberation) who remained off dialysis during follow-up or up to 90 days.
Largest CRRT Liberation Study So Far
“As far as I know, this is the largest study to date that looked at criteria surrounding CRRT liberation,” commented Rewa, and the results “further cement” prior observations from smaller studies.
The factors the researchers identified as linked with better CRRT liberation success were all identified before, “but this is more confirmation” of variables to consider when planning attempted liberation, such as patients who were less sick on ICU admission, those with a shorter duration of CRRT, and patients with higher urinary output just before the liberation attempt, he noted.
The review is also notable in its reliance on observational, real-world data. This means it is pragmatic, which should enhance its generalizability, said Rewa. It’s a very good example of how to exploit “big data” to address questions about CRRT liberation, he added, referring to the more than 100,000 ICU patients that the Mayo group used to mine the data analyzed.
But the study also has limitations, starting with its eligibility window of over 11 years, during which there were “huge changes in practice,” especially in the approach many centers take when starting CRRT in ICU.
CRRT Versus Other Dialysis Methods
The study was also limited by focusing exclusively on CRRT and not on two alternative dialysis options also used to treat ICU patients with AKI: intermittent hemodialysis and sustained low-efficiency dialysis.
Authors of a 2018 review write that “there is still controversy on the superiority of one RRT modality over another in terms of clinical outcomes in patients with AKI in ICU.”
Kashani maintained that CRRT “is the recommended modality of dialysis for hemodynamically unstable patients. At Mayo Clinic, CRRT is viewed as the modality of choice.”
Rewa agreed that “CRRT is the primary form of acute dialysis worldwide,” but also cited “an ongoing debate in critical care nephrology whether CRRT is better or necessary. Some centers get away without having CRRT available,” he noted.
As a result, the Mayo study “is important because it validates CRRT but is limited by not including other dialysis modalities.”
Other study limitations include missing data for some participants (baseline serum creatinine values were unavailable for 39% of included patients); the retrospective design, which means uncontrolled biases could affect the observations; and reliance on data from a single center, which could introduce institutional bias, Rewa said.
The study has received no commercial funding. Kashani has reported no relevant financial relationships. Rewa has reported being a consultant for Baxter Healthcare and Leadiant Biosciences.
Mayo Clin Proc. 2021;96:2757-2767. Full text
Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. @mitchelzoler
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