Designing acute kidney injury clinical trials

Acute kidney injury (AKI) is a common clinical condition with various causes and is associated with increased mortality. Despite advances in supportive care, AKI increases not only the risk of premature death compared with the general population but also the risk of developing chronic kidney disease and progressing towards kidney failure. Currently, no specific therapy exists for preventing or treating AKI other than mitigating further injury and supportive care. To address this unmet need, novel therapeutic interventions targeting the underlying pathophysiology must be developed. New and well-designed clinical trials with appropriate end points must be subsequently designed and implemented to test the efficacy of such new interventions. Herein, we discuss predictive and prognostic enrichment strategies for patient selection, as well as primary and secondary end points that can be used in different clinical trial designs (specifically, prevention and treatment trials) to evaluate novel interventions and improve the outcomes of patients at a high risk of AKI or with established AKI. Several factors complicate the identification of effective interventions that can improve the outcomes of patients with acute kidney injury (AKI). Here, the authors discuss key design considerations for clinical trials in hospitalized patients with AKI, including the selection of adequate patient cohorts and study end points. Acute kidney injury (AKI) is a very heterogeneous syndrome; therefore, enrichment strategies are required to reduce heterogeneity within the study patient cohort and to reduce sample size. Several factors, including risk scores, biomarkers and clinical features, can be used for prognostic and predictive enrichment.Careful selection of end points is crucial for any trial. Different end points are required for phase II and phase III trials, and for prevention, attenuation and treatment trials.The occurrence of AKI is a key end point in prevention or attenuation trials and is mainly assessed based on current AKI definitions (based on serum creatinine and urine output) but biomarkers can be used as surrogate end points in phase II trials.Major adverse kidney events cannot be used in prevention trials, but different components in this composite end point should always be reported when used in treatment trials.The trajectory of AKI is an important outcome in intervention trials, because clinical measures or drugs might influence the course of AKI and subsequently influence the mortality rate.

Automated summary

Acute kidney injury (AKI) is a common clinical condition associated with increased mortality and the risk of developing chronic kidney disease and kidney failure. Currently, there is no specific therapy for AKI and novel interventions targeting the underlying pathophysiology are needed. Well-designed clinical trials with appropriate end points are crucial to evaluate the efficacy of these new interventions and improve outcomes.