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

Daniel Lazzareschi; Ravindra L Mehta; Laura M Dember; Juliane Bernholz; Alparslan Turan; Amit Sharma; Sachin Kheterpal; Chirag R Parikh; Omar Ali; Ivonne H Schulman; Abigail Ryan; Jean Feng; Noah Simon; Romain Pirracchio; Patrick Rossignol; Matthieu Legrand

doi:10.1093/ndt/gfac003

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

Nephrol Dial Transplant. 2023 Mar 31;38(4):834-844. doi: 10.1093/ndt/gfac003.

Authors

Daniel Lazzareschi¹, Ravindra L Mehta², Laura M Dember³, Juliane Bernholz⁴, Alparslan Turan^{5

6}, Amit Sharma⁷, Sachin Kheterpal⁸, Chirag R Parikh⁹, Omar Ali^{10

11}, Ivonne H Schulman¹², Abigail Ryan¹³, Jean Feng¹⁴, Noah Simon¹⁵, Romain Pirracchio¹, Patrick Rossignol^{16

17}, Matthieu Legrand^{1

16}

Affiliations

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

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.

Keywords: AKI; biomarkers; machine learning; outcome; pragmatic trial.

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

Acute Kidney Injury* / diagnosis
Acute Kidney Injury* / etiology
Acute Kidney Injury* / therapy
Humans
Prognosis

Abstract

Publication types

MeSH terms

Grants and funding