Early Dialysis in Critical Kidney Injury Doesn’t Improve Outcomes

Early Dialysis in Critical Kidney Injury Doesn’t Improve Outcomes
Critically ill patients with severe acute kidney injury (AKI) who undergo dialysis as soon as possible after meeting eligibility criteria do not have a lower risk for death at 90 days than patients for whom dialysis is discouraged, a multinational, randomized trial indicates.

“Starting too early could mean that this costly treatment might be used in patients who would have survived and recovered kidney function anyway,” said Martin Gallagher, MBBS, MPH, PhD, program director, Acute Kidney Injury and Trials, the George Institute, in New South Wales, Australia, who is one of the investigators in this global trial.

The results were published online July 15 in The New England Journal of Medicine.

“This study gives clinicians confidence that in patients with acute kidney injury where dialysis is appropriate but not urgent, waiting to start dialysis is likely to be safe and may reduce the need for this valuable but invasive treatment,” he added in a statement from his institution.

The STARRT-AKI Trial Conducted in 15 Countries

The Standard Versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) study was carried out at 168 different hospitals in 15 countries.

Patients had been admitted to an ICU with definitive kidney dysfunction. They were randomly assigned either to a group for which an accelerated strategy for the initiation of renal replacement therapy (RRT) — dialysis — was employed, or to a group for which a standard strategy of dialysis initiation was used.

“In the accelerated-strategy group, clinicians were to start renal-replacement therapy as soon as possible and within 12 hours after patients had met full eligibility criteria,” the investigators explain.

Dialysis was initiated at a median of 6.1 hours after determination of full eligibility in 96.8% of accelerated-strategy patients.

For those assigned to the standard-strategy group, physicians were discouraged from initiating dialysis until patients met one of the following criteria:

  • A serum potassium level of ≥6.0 mmol/L

  • A pH of ≤7.20

  • A serum bicarbonate level of ≤12 mmol/L

  • Evidence of severe respiratory failure

  • Clinical perception of volume overload

  • Persistent AKI for at least 72 hours after randomization

In the standard-strategy group, dialysis was started at a median of 31.1 hours after determination of full eligibility in 61.8% of patients.

The modified intention-to-treat analysis included 1465 patients in the accelerated-strategy group and 1462 in the standard-strategy group.

No Difference in Primary Endpoint

“The primary outcome was death from any cause at 90 days after randomization,” the team writes.

This occurred in 43.9% of patients assigned to the accelerated-strategy group and in 43.7% of patients in the standard-strategy group, for an absolute risk difference of 0.2 percentage points between the two groups.

Among survivors at 90 days, the rate of continued dependence on renal replacement therapy was 70% higher among those in the accelerated-strategy group, of whom 85 of 814 patients (10.4%) were still on dialysis, compared with 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 – 2.43).

In contrast, there were no meaningful differences in the composite of death or dialysis dependence, major adverse kidney events at 90 days, or death in the ICU at 28 days between the two treatment groups.

“Patients in the accelerated-strategy group had a shorter ICU stay than those in the standard-strategy group,” the team acknowledges.

However, no major differences were seen between the two groups in the number of ventilator-free days, vasoactive-free days, or ICU-free days at 28 days, they add.

Adverse events were 40% more likely to occur in the accelerated-strategy group, at 23%, compared with 16.5% of the standard-strategy group. Hypotension and hypophosphatemia were the most common adverse events for which there was a significant between-group difference.

Confidence That Taking a Conservative Approach to Treatment Is OK

The authors state that the fact that more of the survivors who were assigned to the accelerated strategy continued to be dependent on dialysis at 90 days than those in the standard-strategy arm suggests that greater exposure to renal replacement therapy may compromise kidney repair and the return of endogenous kidney function.

There was no apparent difference in quality of life between the two groups.

“This [study] clarifies a long-standing clinical dilemma regarding the treatment strategy for critically ill patients with acute kidney injury who have no overt complications that would mandate the immediate initiation of renal-replacement therapy,” the investigative team notes.

“Studying a large number of patients from many countries across different hospital settings gives us a degree of confidence that taking a more conservative approach to treatment may be warranted,” Gallagher concludes.

The study was funded by the Canadian Institutes of Health Research. The authors have disclosed no relevant financial relationships.

N Engl J Med. Published online July 15, 2020. Abstract

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