Professor Martin Gallagher
Australian nephrologists and intensivists are among those calling for adaptive platform trials in AKI to help translate the boom in kidney discovery research into novel therapies and improved clinical outcomes.
The call for investment in innovative trial designs, as demonstrated in oncology and cardiovascular disease, accompanied a mapping review of kidney research publications indexed in EMBASE from 1 January 2013 to 31 December 2024.
The review, published in the Journal of Critical Care [link here], found that overall kidney research output increased across the 12-year study period.
Basic science articles decreased slightly as a proportion, from 31.4% to 29.6%, however within that, AKI-related basic science articles increased from 5.9% to 12.1%.
The study also found the proportion of AKI-related basic science articles that focused on mechanistic insights rose from 24.7% to 36% while those focussing on therapeutics had a more modest increase from 60.7% to 71.2%.
“Together, these trends suggest that, despite a relative decline in basic science as a proportion of all kidney research, AKI-specific discovery science is becoming more prominent and increasingly oriented toward potential therapeutic targets,” it said.
The authors, including Professor Martin Gallagher from UNSW Sydney and the George Institute for Global Health, said increased discovery activity alone was unlikely to translate into improved outcomes without appropriate trial infrastructure.
“Traditional, sequential RCTs are often slow, resource-intensive, and underpowered for heterogeneous syndromes such as AKI, particularly when multiple promising interventions must be evaluated,” they said.
“Master protocols, including adaptive platform trials, umbrella trials, and basket trials, offer an alternative framework in which multiple therapies, and sometimes multiple populations, can be studied efficiently under a single overarching protocol, with shared controls and the ability to add or discontinue interventions over time.”
They said the ICU, with high rates of AKI and close monitoring and timely biomarker sampling of patients, was an important setting for prevention and treatment trials.
“At the same time, ICU cohorts are highly heterogeneous, and aggregating biologically distinct subgroups into broad syndromic categories can obscure treatment effects. Within ICU and non-ICU populations alike, stratification by aetiology, baseline risk, and biomarker-defined endotypes is likely to be essential.”
They concluded that the AKI research community was increasingly generating the types of insights and candidate interventions that could underpin precision medicine strategies.
“To convert this expanding discovery pipeline into improved patient outcomes, future efforts will need to focus on developing and implementing efficient, flexible clinical trial structures that can evaluate multiple interventions across heterogeneous AKI populations in a timely manner.”