Table 2.

Proposed endpoints for AKI trials

Endpoint	Advantages	Limitations	Suggested applications
AKI stage 1	● Sensitive (frequent) endpoint, accommodating smaller sample size ● Associated with mortality in certain settings	● Not a patient-centered outcome ● May lack specificity ● Has been associated with better outcomes (mortality) in certain settings (e.g. in heart failure) ● Not conventionally used as an outcome for Phase 3 licensing studies	● Primary endpoint for preventive studies ● Secondary endpoint for safety studies
Severe AKI	● Specific to kidney damage ● Associated with mortality	● Occurs less frequently, requiring larger sample size ● Not a patient-centered outcome ● Not conventionally used as an outcome for Phase 3 licensing studies	● Primary endpoint for preventive strategies ● Secondary endpoint for safety studies
Change in glomerular filtration rate	● Sensitive (frequent) endpoint, accommodating smaller sample size	● Not a patient-centered outcome ● Requires accurate measurement	● Primary or secondary endpoint for early phase trials
Renal recovery	● Sensitive (frequent) endpoint, accommodating smaller sample size ● Associated with mortality	● Definition of this outcome may vary, allowing for potential misclassification	● Primary or secondary endpoint for therapeutic studies in patients with recognized AKI
Sustained loss of renal function	● Sensitive (frequent) endpoint, accommodating smaller sample size	● Requires accurate measurement	● Primary or secondary endpoint in patients with recognized AKI
Renal replacement therapy (RRT)	● Associated with mortality ● Associated with resource utilization ● Patient-centered outcome	● Indications vary between institutions and providers; use of RRT is a clinical decision and not a pathophysiologic entity per se ● Susceptible to survivorship bias	● Secondary endpoint for therapeutic studies in patients with recognized AKI ● Recommend defining strict criteria for initiation ● Consider combining with ‘days alive’
Death (28-day all-cause mortality)	● Hard, patient-centered outcome	● Cause of death may not directly result from AKI ● Rare event requiring large sample size	● Primary or secondary endpoint for therapeutic studies in patients with recognized AKI
Major Adverse Kidney Events at 90 days (MAKE-90)	● Patient-centered outcome ● Occurs more frequently than individual component events	● May be driven by death and not directly related to AKI ● Low incidence in certain populations	● Primary or secondary endpoint for therapeutic studies in patients with recognized AKI
Chronic kidney disease	● Patient-centered outcome	● Low incidence can require large sample size ● Requires longer follow-up time ● Costly	● Primary or secondary endpoint for therapeutic studies in patients with recognized AKI
Cardiovascular events	● Patient-centered outcome	● May not directly result from AKI ● Susceptible to survivorship bias, especially short-term cardiovascular events	● Primary or secondary endpoint for therapeutic studies in patients with recognized AKI ● Consider combining with death or ‘days alive’