In the largest international study of its kind, researchers at the University of Alberta and Toronto's St. Michael's Hospital found that an accelerated renal-replacement therapy strategy did not reduce mortality after three months, compared to a standard strategy for critically ill patients with acute kidney injury.
The Standard vs. Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial was co-led by Sean Bagshaw, professor and chair of the University of Alberta's Department of Critical Care Medicine, and Ron Wald, nephrologist and medical director of hemodialysis at St. Michael's and associate professor of medicine at the University of Toronto. STARRT-AKI enrolled 3,019 patients across 168 hospitals in 15 countries.
"This is the largest trial to tackle a question that has been vexing clinicians for more than 30 years," said Bagshaw. "The critical care and nephrology communities have been eagerly awaiting further information to guide the question, 'When is the ideal time to start dialysis therapy in critically ill patients admitted to Intensive Care Unit (ICU) with acute kidney injury?'"
A sudden loss of kidney function--a condition known as acute kidney injury--frequently affects patients who are admitted to the intensive care unit. When acute kidney injury is severe, kidney function may be replaced by dialysis machines that remove toxins and excess fluid and salts that accumulate in the bloodstream. There is no universal consensus on the optimal time to start such therapy.
In STARRT-AKI, patients admitted to the ICU who experienced severe acute kidney injury were randomly assigned to one of two treatment strategies. One strategy looked at pre-emptive or accelerated initiation of renal replacement therapy, in which patients received renal-replacement therapy almost immediately upon fulfilling eligibility. The second treatment strategy used a more conservative approach, which entailed observing the patient and initiating renal-replacement therapy only if the patient developed complications or had persistence of acute kidney injury beyond three days.
The team found that 43.9 per cent of patients in the accelerated strategy and 43.7 per cent of patients in the standard strategy died by 90 days, showing that there was no significant difference in survival between the two treatment strategies.
"Because little evidence existed previously, clinicians around the world were approaching the initiation of dialysis very differently," said Wald. "We hope that this definitive evidence can help clinicians make more informed decisions."
"Dialysis is life-saving, but it has potential harms. By initiating it more judiciously, it will expose patients to less risk and potentially reduce health-care costs without any negative impact on patient survival," Wald said.
The study also looked at several subgroups of patients--including their sex, where they live, presence of chronic kidney disease, whether they had sepsis and the severity of illness at presentation--to try to understand whether there was evidence that any patient group benefited from the accelerated strategy versus the standard strategy. Again, they did not find any substantial difference in survival between the two approaches. They did, however, find that at the 90-day endpoint, patients who had received the accelerated strategy were slightly more likely to remain dependent on dialysis than patients who received the standard strategy.
"About 10 per cent of patients in the accelerated strategy remained dialysis-dependent versus six per cent who received the standard strategy," Bagshaw said.
The trial was one of the largest coordinated by the Applied Health Research Centre at St. Michael's, an organization that helps design, coordinate and manage large clinical trials around the world.
The team said they hope to do further research with this data to better understand how different factors impact outcomes in this population and develop further insights about how to best deliver dialysis to this high-risk population.
"Ultimately what is most important is how we can use these results to improve the care of critically ill patients with acute kidney injury at the bedside," Bagshaw said.
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The STARRT-AKI trial was funded by the Canadian Institutes of Health Research, the Australian National Health and Medical Research Council, the Health Research Council of New Zealand, the United Kingdom National Institutes for Health Research and by an unrestricted grant from Baxter in partnership with the Canadian Institutes of Health Research.
Journal
New England Journal of Medicine