Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases

Zaid K Yousif; Jejo D Koola; Etienne Macedo; Jorge Cerda; Stuart L Goldstein; Rajasekara Chakravarthi; Andrew Lewington; David Selewski; Michael Zappitelli; Dinna Cruz; Ashita Tolwani; Melanie S Joy; Vivekanand Jha; Raja Ramachandran; Marlies Ostermann; Bhavna Pandya; Anjali Acharya; Patrick Brophy; Daniela Ponce; Julia Steinke; Josee Bouchard; Carlos E Irarrazabal; Romina Irarrazabal; Andrés Boltansky; David Askenazi; Nitin Kolhe; Rolando Claure-Del Granado; Nadine Benador; Clare Castledine; Andrew Davenport; Jonathan Barratt; Sunil Bhandari; Alyssa A Riley; T K Davis; Christopher Farmer; Michael Hogarth; Mark Thomas; Patrick T Murray; Cassianne Robinson-Cohen; Paola Nicoletti; Sucheta Vaingankar; Ravindra Mehta; Linda Awdishu

doi:10.1016/j.ekir.2023.07.037

Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases

Kidney Int Rep. 2023 Aug 14;8(11):2333-2344. doi: 10.1016/j.ekir.2023.07.037. eCollection 2023 Nov.

Authors

Zaid K Yousif¹, Jejo D Koola^{2

3}, Etienne Macedo⁴, Jorge Cerda^{5

6}, Stuart L Goldstein^{7

8}, Rajasekara Chakravarthi⁹, Andrew Lewington¹⁰, David Selewski¹¹, Michael Zappitelli¹², Dinna Cruz⁴, Ashita Tolwani¹³, Melanie S Joy¹⁴, Vivekanand Jha^{15

16

17}, Raja Ramachandran¹⁸, Marlies Ostermann¹⁹, Bhavna Pandya²⁰, Anjali Acharya²¹, Patrick Brophy²², Daniela Ponce²³, Julia Steinke²⁴, Josee Bouchard²⁵, Carlos E Irarrazabal²⁶, Romina Irarrazabal²⁷, Andrés Boltansky²⁷, David Askenazi²⁸, Nitin Kolhe²⁹, Rolando Claure-Del Granado³⁰, Nadine Benador³¹, Clare Castledine³², Andrew Davenport³³, Jonathan Barratt³⁴, Sunil Bhandari³⁵, Alyssa A Riley³⁶, T K Davis³⁷, Christopher Farmer³⁸, Michael Hogarth², Mark Thomas³⁹, Patrick T Murray⁴⁰, Cassianne Robinson-Cohen⁴¹, Paola Nicoletti⁴², Sucheta Vaingankar⁴³, Ravindra Mehta⁴, Linda Awdishu¹

Affiliations

¹ Division of Clinical Pharmacy, University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical, La Jolla, California, USA.
² Division of Biomedical Informatics, Department of Medicine, University of California, La Jolla, California, USA.
³ Division of Hospital Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
⁴ Division of Nephrology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
⁵ Albany Medical College, Albany, New York, USA.
⁶ St. Peter's Hospital Partners, Albany, New York, USA.
⁷ Center for Acute Care Nephrology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
⁸ University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁹ Nephrology Services, STAR Hospitals, Renown Clinical Services, Hyderabad, Telangana, India.
¹⁰ St. James University Hospital, Leeds, UK.
¹¹ Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA.
¹² Department of Pediatrics, Division of Nephrology, Hospital for Sick Children, University of Toronto, Ontario, Canada.
¹³ University of Alabama at Birmingham, Alabama, USA.
¹⁴ University of Colorado School of Pharmacy and Pharmaceutical Sciences and School of Medicine in Aurora, Colorado, USA.
¹⁵ George Institute for Global Health, UNSW, New Delhi, India.
¹⁶ School of Public Health, Imperial College, London, UK.
¹⁷ Prasanna School of Public Health, MManipal Academy of Higher Education, Manipal, India.
¹⁸ Postgraduate Institute of Medical Education & Research, Chandigarh, India.
¹⁹ Department of Critical Care and Nephrology, King's College London, Guy's and St Thomas' Hospital, London, UK.
²⁰ Medical and Dental Staff Governor, Liverpool University Hospitals NHS Foundation Trust/Aintree University Hospital, Liverpool, UK.
²¹ Jacobi Medical Center, Albert Einstein College of Medicine, The Bronx, New York, New York, USA.
²² Department of Pediatrics at the University of Rochester School of Medicine and Dentistry, New York, USA.
²³ University of Sao Paulo State, Brazil.
²⁴ Helen DeVos Children's Hospital, Grand Rapids, Michigan, USA.
²⁵ Hopital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada.
²⁶ Programa de Fisiología, Centro de Investigación e Innovación Biomédica, Universidad de los Andes, Santiago, Chile.
²⁷ Clinica Dávila, Santiago, Chile.
²⁸ Children's of Alabama (UAB-Pediatrics), Birmingham, Alabama, USA.
²⁹ Consultant Nephrologist, Royal Derby Hospital, Derby, UK.
³⁰ Division of Nephrology Hospital Obrero No 2 - CNS Cochabamba, Bolivia/Universidad Mayor de San Simón School of Medicine Cochabamba, Bolivia.
³¹ University of California San Diego, San Diego, California, USA / Rady Children's Hospital, San Diego, USA.
³² Brighton and Sussex Medical School, Brighton, East Sussex, UK.
³³ University College London, Department of Renal Medicine, Royal Free London NHS Trust London, UK.
³⁴ Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
³⁵ Hull University Teaching Hospitals NHS Trust, Hull, UK.
³⁶ Department of Pediatrics, Section of Nephrology, Baylor College of Medicine, Houston, Texas, USA.
³⁷ St. Louis Children's Hospital, St. Louis, Missouri, USA.
³⁸ Centre for Health Services Studies, George Allen Wing, Cornwallis Building, University of Kent, Canterbury, Kent, UK.
³⁹ Birmingham Heartlands Hospital, Birmingham, Alabama, USA.
⁴⁰ School of Medicine, University College Dublin, Ireland.
⁴¹ Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Tennessee, USA.
⁴² Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
⁴³ University of California, La Jolla, California, USA.

Abstract

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI.

Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC).

Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86).

Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Keywords: drug-induced acute kidney injury; nephrotoxicity.

Grants and funding

T15 LM011271/LM/NLM NIH HHS/United States