SAN DIEGO—Data conflict on whether early renal replacement therapy (RRT) results in better outcomes in critically ill patients with acute kidney injury (AKI).

In an oral presentation at the 2011 annual meeting of the Society for Critical Care Medicine, Tim Bunchman, MD, discussed data from a meta-analysis that he reviewed showing that early RRT significantly reduces mortality. However, in a poster presented at the conference, Constantine Karvellas, MD, and colleagues reported on a meta-analysis of 15 adult early RRT studies revealing significant heterogeneity in study design. The researchers concluded that the jury is still out on the benefits of early RRT.

Dr. Bunchman, Professor and Director of Pediatric Nephrology, Children’s Hospital of Richmond, Virginia Commonwealth University School of Medicine, conceded that fuzziness remains in the field due to both confounding factors and disparities in AKI definitions from study to study. However, he still believes the data overwhelmingly support the salubrious effects of early RRT.

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“One of the questions that came up after our presentations at the meeting was from an intensivist who stated his belief that every time you put patients on RRT they stop producing urine and so you reduce their recoverability,” Dr. Bunchman told Renal & Urology News. “That’s a common perception. But the data presented, including a 2008 meta-analysis, showed there is actually a higher survival rate in patients with early renal replacement therapy.”

Dr. Bunchman laid out the main points of the meta-analysis that supports the use of early RRT, which was published in the American Journal of Kidney Diseases (2008;52:272-284). This meta analysis sorted through 4,182 potentially relevant studies before arriving at 23 that met inclusion criteria, such as being a randomized controlled trial or a prospective or retrospective cohort study. Patients on early RRT had a statistically significant 28% lower risk of mortality and a 22% higher probability of renal recovery than those receiving RRT later. He also described six studies showing that lower fluid overload and early RRT are associated with improved outcomes.

Dr. Bunchman concluded that a high level of cooperation between pediatric intensivists and nephrologists is needed to optimize the timing of RRT initiation and hence improve patient care and survival. Additionally, he noted that the emergence of neutrophil gelatinase associated lipocalin (NGAL) as an early biomarker of the development of AKI is important for more accurately determining the onset of of AKI and perhaps the optimal time to start RRT.

The study presented by Dr. Karvellas, an assistant professor in the Division of Critical Care Medicine, University of Alberta, Edmonton, summarized the main information from the 15 adult high-highest-quality RRT studies that have been published. Only two were randomized trials.

The analysis showed a statistically significant 28% lower risk of mortality with early versus later initiation of RRT. However, Dr. Karvellas and his group found a highly significant amount of heterogeneity between the studies. They concluded that, in the absence of new evidence from high-quality, randomized trials, a definitive treatment recommendation cannot be made.

“Well-designed randomized studies targeting acceptable ‘early’ RRT criteria compared with standard of care in homogeneous patient populations are needed to definitively determine the effect on patient outcomes,” Dr. Karvellas told Renal & Urology News after the meeting.

Commenting on the presentations, Ron Wald, MD, MPH, Assistant Professor of Medicine in the Division of Nephrology at the University of Toronto, said clinical practice should not be changed until stronger evidence for the efficacy of early RRT is available.

“In observational studies, there may be a lot of other factors associated with the receipt of earlier RRT that are actually mediating the more favorable outcomes rather than the receipt of early RRT itself,” Dr. Wald said. “Given the potential for confounding, I would be very cautious about interpreting the studies to date and would await definitive answers from well-designed randomized trials.”