Overcoming barriers in the design and implementation of clinical trials for acute kidney injury: a report from the 2020 Kidney Disease Clinical Trialists meeting

Author:

Lazzareschi Daniel1,Mehta Ravindra L2,Dember Laura M3,Bernholz Juliane4,Turan Alparslan56,Sharma Amit7,Kheterpal Sachin8,Parikh Chirag R9ORCID,Ali Omar1011,Schulman Ivonne H12,Ryan Abigail13,Feng Jean14,Simon Noah15,Pirracchio Romain1,Rossignol Patrick1617,Legrand Matthieu116ORCID

Affiliation:

1. Department of Anesthesia & Perioperative Care, Division of Critical Care Medicine, University of California, San Francisco (UCSF) , San Francisco, CA , USA

2. Department of Medicine, University of California , San Diego, San Diego, CA , USA

3. Renal-Electrolyte and Hypertension Division, Department of Medicine, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine , Pennsylvania, PA , USA

4. AM-Pharma , Utrecht , The Netherlands

5. Department of Anesthesiology, Lerner College of Medicine of Case Western University , Cleveland, OH , USA

6. Department of Outcomes Research, Cleveland Clinic , Cleveland, OH , USA

7. Bayer Pharmaceuticals , Cambridge, MA , USA

8. Department of Anesthesiology, University of Michigan , Ann Arbor, MI , USA

9. Department of Medicine, Johns Hopkins School of Medicine , Baltimore, MD , USA

10. Verpora Ltd , Nottingham , UK

11. University of Portsmouth , UK

12. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) , Bethesda, MD , USA

13. Division of Chronic Care Management, Centers for Medicare & Medicaid Services , Woodlawn, MD , USA

14. Department of Epidemiology and Biostatistics, University of California, San Francisco (UCSF) , San Francisco, CA , USA

15. Department of Biostatistics, University of Washington (UW) , Seattle, WA , USA

16. INI-CRCT Network , Nancy , France

17. University of Lorraine, Inserm 1433 CIC-P CHRU de Nancy , Inserm U1116, Nancy , France

Abstract

ABSTRACT Acute kidney injury (AKI) is a growing epidemic and is independently associated with increased risk of death, chronic kidney disease (CKD) and cardiovascular events. Randomized-controlled trials (RCTs) in this domain are notoriously challenging and many clinical studies in AKI have yielded inconclusive findings. Underlying this conundrum is the inherent heterogeneity of AKI in its etiology, presentation and course. AKI is best understood as a syndrome and identification of AKI subphenotypes is needed to elucidate the disease's myriad etiologies and to tailor effective prevention and treatment strategies. Conventional RCTs are logistically cumbersome and often feature highly selected patient populations that limit external generalizability and thus alternative trial designs should be considered when appropriate. In this narrative review of recent developments in AKI trials based on the Kidney Disease Clinical Trialists (KDCT) 2020 meeting, we discuss barriers to and strategies for improved design and implementation of clinical trials for AKI patients, including predictive and prognostic enrichment techniques, the use of pragmatic trials and adaptive trials.

Funder

NIH

National Institute of Diabetes and Digestive and Kidney Diseases

Department of Health and Human Services

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

Reference72 articles.

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2. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study;Hoste;Intensive Care Med,2015

3. Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational cross-sectional study;Mehta;Lancet,2016

4. Acute kidney injury in the critically ill: an updated review on pathophysiology and management;Pickkers;Intensive Care Med,2021

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