Timing of Kidney Replacement Therapy Initiation in Acute Kidney Injury

Alejandro Y. Meraz-Muñoz; Sean M. Bagshaw; Ron Wald


Curr Opin Nephrol Hypertens. 2021;30(3):332-338. 

In This Article

Standard Versus Accelerated Initiation of Renal-replacement Therapy in Acute Kidney Injury Trial

The Standard Versus Accelerated initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial was conducted at 168 centers in 15 countries, and tested the hypothesis that an accelerated strategy of KRT initiation would confer a reduction in 90-day all-cause mortality as compared with a standard strategy.[32] This study included individuals with stage 2--3 AKI; however, in contrast with previous trials, eligibility was not dependent on the duration of AKI. Key exclusions included overt indications for KRT initiation, lack of commitment to offer KRT and preexisting advanced CKD. Patients were provisionally eligible if they met the main inclusion criteria and had none of the core exclusion criteria. The final step to full eligibility depended on individual clinician equipoise: attending clinicians were asked whether they perceived that a patient either needed immediate KRT initiation or that deferral of KRT was mandated because of the anticipation of forthcoming recovery of kidney function. The presence of one of these conditions implied a lack of clinical equipoise by the clinicians and led to exclusion of the patients. Whereas this approach may have led to some degree of heterogeneity in the recruited population, clinician involvement in the final stages of eligibility determination helped to ensure that the trial enrolled patients for whom there was true uncertainty about the timing of KRT initiation. Once clinicians confirmed the eligibility of the patients, they were randomized to an accelerated strategy (KRT to be commenced within 12 h of becoming fully eligible) or a standard strategy, which discouraged clinicians from commencing KRT unless one or more of the following criteria developed: serum potassium at least 6.0 mmol/l, pH 7.20 or less, serum bicarbonate 12 mmol/l or less or respiratory failure (ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen ≤200) because of fluid overload. If AKI persisted for more than 72 h, the decision to initiate KRT shifted to the sole discretion of the attending physician. Unlike the previous trials, the standard-strategy arm did not include a protocolized obligation to commence KRT even if one of the aforementioned conditions was met.

Amongst the 3019 randomized patients, 2927 (1465 and 1462 in the accelerated and standard strategies, respectively) were included in the modified intention-to-treat analysis. The vast majority of patients randomized to the accelerated-strategy arm commenced KRT with a median time from full eligibility of 6 h, whereas 62% of standard-strategy participants initiated KRT with a median time from eligibility of 31 h. The primary outcome of 90-day all-cause mortality was 43.9% in the accelerated arm versus 43.7% in the standard arm [relative risk (RR) 1.00; 95% CI 0.93–1.09]. These findings were consistent across all-prespecified sub-groups including those with and without sepsis. There was no evidence of heterogeneity of treatment effect across categories of illness acuity. Among survivors, there was a significantly higher likelihood of persistent dialysis dependence at 90 days in patients randomized to the accelerated strategy (10.4 versus 6.0% in the standard arm; RR 1.74, 95% CI 1.24–2.43). Adverse events were more common in the accelerated arm (23 versus 16.5%), mainly driven by hypotension and hypophosphatemia. There was a trend for increased blood stream infections in the accelerated strategy, but it did not reach statistical significance.