STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI): A Multi-Centre, Randomized, Controlled Trial

Acute kidney injury (AKI) occurs in up to 20% of patients treated in intensive care units (ICU). When severe, it requires renal replacement therapy (RRT) and is associated with high healthcare costs and a high mortality. Beyond the acute high mortality, survivors of AKI carry long-term greater risks of mortality, requirement for institutional care and the development of chronic and end stage kidney disease. There are currently no proven treatments that reduce the burden of morbidity or mortality with AKI.

The acute delivery of RRT to critically ill patients with AKI is common practice; yet there have been controversies regarding the optimal delivery of RRT for these patients. A number of randomised clinical trials have examined the delivered dose/intensity of RRT, RRT modality and RRT clearance mode. However, characterisation of the optimal time to initiate RRT, in particular whether earlier initiation translates into improved clinical outcomes, remains uncertain, and is a clear priority for higher quality evidence.

 Absolute indications for initiating RRT such as hyperkalemia and overt uremic symptoms are well recognised, but the optimal time for initiating RRT in patients without a life-threatening complication of AKI is still unknown. Earlier initiation of RRT in critically ill patients with AKI may confer better control of uraemia, acid-base homeostasis, electrolyte imbalances, extracellular volume accumulation and systemic inflammation. On the other hand, early RRT commencement might potentially impede patient’s spontaneous recovery of renal function and expose them to the risks of RRT while inflating costs.

Numerous studies over the last few decades have attempted to resolve the issue of optimal timing, however the level of evidence guiding current practice remains weak, derived primarily from retrospective and observational cohort studies and small, underpowered prospective trials. The optimal timing of RRT initiation is an existing knowledge gap and a clear priority for investigation. In the absence of robust predictive markers, earlier initiation of RRT may increase the risk of exposing patients to RRT who might otherwise recover kidney function without requiring RRT. As RRT is associated with potential risks and entails significant costs, it is important to determine optimal timing of the therapy. The STARRT-AKI study is designed as a prospective, multicentre, randomised controlled trial to assess whether early RRT initiation is associated with enhanced survival and renal recovery as compared to a standard strategy for initiation of RRT, which is driven by conventional indications and clinician judgement.

The STARRT-AKI Study will compare immediate initiation of RRT with a delayed approach to initiation of RRT for patients with severe AKI in ICU to assess the impact upon all-cause mortality at 90 days.

2,866 participants will be recruited globally, from over 100 sites throughout Australia, New Zealand, China, Canada, Europe, the United States and South America.

The study population will consist of adult patients admitted to intensive care units with severe AKI who meet the full eligibility criteria for RRT.

STARRT-AKI is coordinated in collaboration with project originators Sean Bagshaw (University of Alberta) and Ron Wald (St Michael’s Hospital, University of Toronto) and the Applied Health Research Centre at St Michael’s Hospital in Toronto, Canada. The George Institute is a Regional Coordinating Centre, managing sites in Australia, New Zealand and China.