STARRT-AKI: Is early better than delayed renal-replacement therapy in AKI patients?

An accelerated renal-replacement strategy does not appear to reduce the risk of mortality at 90 days among critically ill patients with acute kidney injury (AKI) compared to a standard strategy, according to the results of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial.

“This finding clarifies a long-standing clinical dilemma regarding the treatment strategy for critically ill patients with AKI who have no overt complications that would mandate the immediate initiation of renal-replacement therapy,” the researchers said. [Lancet 1961;1:129-134]

Results of this multinational, randomized, controlled trial were presented by lead researchers Sean M. Bagshaw and Ron Wald at the recently concluded virtual Critical Care Reviews Meeting 2021 (eCCR21).

STARRT-AKI randomized 3,019 patients to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or AKI persisted for >72 hours). Death from any cause at 90 days was the primary outcome.

Of the participants, 2,927 (97.0 percent) were included in the modified intention-to-treat analysis (1,465 in the accelerated strategy group and 1,462 in the standard therapy group). Renal-replacement therapy was carried out in 1,418 (96.8 percent) and 903 (61.8 percent) patients in the accelerated and standard strategy groups, respectively.

At 90 days, 643 patients (43.9 percent) who received the accelerated strategy and 639 (43.7 percent) on standard care died (relative risk [RR], 1.00, 95 percent confidence interval [CI], 0.93–1.09; p=0.92). Among survivors, 85 of 814 patients (10.4 percent) in the accelerated strategy arm and 49 of 815 (6.0 percent) in the standard strategy arm continued dependence on renal-replacement therapy (RR, 1.74, 95 percent CI, 1.24–2.43). [N Engl J Med 2020;383:240-251]

In the respective groups, adverse events were reported in 346 of 1,503 (23.0 percent) and 245 of 1,489 (16.5 percent) patients (p<0.001).

Observational studies using different biochemical thresholds as surrogates for the timing of initiation and a single-centre randomized trial of surgical patients showed that earlier renal-replacement therapy was associated with a lower mortality than delayed therapy. [JAMA 2016;315:2190-2199; J Crit Care 2009;24:129-140; Clin J Am Soc Nephrol 2006;1:915-919; Clin J Am Soc Nephrol 2014;9:1577-1585]

On the other hand, two multicentre randomized trials suggested that an early strategy did not result in a lower mortality risk compared to a delayed strategy. [N Engl J Med 2018;379:1431-1442; N Engl J Med 2016;375:122-133]

Eligibility in these two trials was met by fulfilling consensus-defined serum creatinine levels and urine-output thresholds for severe AKI, with renal-replacement therapy initiated promptly following determination in the early-therapy group.

“In [the STARRT-AKI] trial, we aimed to enrich our patient population by incorporating clinical equipoise to guide eligibility, rather than relying on defined intervals after the patients fulfilled consensus criteria for severe AKI,” the researchers said.

“This process excluded more than 7,000 patients who had been rated by clinicians as being appropriate candidates for emergency renal-replacement therapy or likely to have imminent recovery of kidney function,” they added.

Moreover, triggers for the initiation of renal-replacement therapy among patients on standard care were not directed by thresholds for severity of AKI or defined time intervals, according to the researchers. [JAMA 2016;315:2190-2199; N Engl J Med 2018;379:1431-1442; N Engl J Med 2016;375:122-133]