Abstract
Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.
Original language | English (US) |
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Article number | e003467 |
Journal | Journal for immunotherapy of cancer |
Volume | 9 |
Issue number | 10 |
DOIs | |
State | Published - Oct 8 2021 |
Funding
Disclaimer Shruti Gupta is a Scientific Coordinator for GlaxoSmithKline’s ASCEND Trial and receives funding from GE Healthcare. Sunil Rangarajan is supported by the 2020 Young Investigator Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology and by the UAB-UCSD O'Brien Center for Acute Kidney Injury Research (NIH P30-DK079337). Kenar D. Jhaveri is a consultant for Astex Pharmaceuticals, Natera, GlaxoSmithKline, ChemoCentryx, and Chinook, a paid contributor to Uptodate.com, and receives honorarium from ISN and ASN. Daniel Sanghoon Shin participates in the speakers’ bureau at Genentech. Sunandana Chandra is on the Advisory Board or Bristol Myers Squibb, EMD Serono, Regeneron, Sanofi Genzyme, Exicure, Pfizer, and Novartis, and on the steering committee for Genentech. Shveta S. Motwani is a Deputy Editor at UpToDate. Naoka Murakami reports funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; K08DK12068) and from the American Society of Nephrology (Carl W. Gottschalk Research Scholar Grant). Frank B. Cortazar is a consultant for ChemoCentryx and Retrophin. Maria J. Soler reports personal fees from NovoNordisk, Jansen, Mundipharma, AstraZeneca, Esteve, Fresenius, Ingelheim Lilly, Vifor, ICU and grants and personal fees from Boehringer. Clara García-Carro has given scientific lectures and participated in advisory boards organized by Astra-Zeneca, Boehringer-Ingelheim Lilly, Mundipharma and NovoNordisk. Ala Abudayyeh and Jamie S. Lin are supported by the Division of Internal Medicine Immuno-Oncology Toxicity Award Program of the University of Texas MD Anderson Cancer Center. Jamie S. Lin is supported by a grant from the National Institutes of Health (NIH; K08DK119466). Ben Sprangers is a senior clinical investigator at the Research Foundation Flanders (F.W.O.) (1842919N) and is supported by Stichting tegen Kanker (grant C/2020/1380). Arash Rashidi is a consultant for Otsuka pharmaceutical company. Ilya Glezerman’s spouse has stock ownership in Pfizer. Sethu M. Madhavan is supported by NIH grant K08 DK123411. Dwight H. Owen is a Paul Calabresi Scholar supported by the OSU K12 Training Grant for Clinical Faculty Investigators (K12 CA133250) and reports research support (to institution) from Bristol Myers Squibb, Merck, Palobiofarma, Genentech. Dr. Owen is also supported in part by The Ohio State University Comprehensive Cancer Center and by the NIH (P30 CA016058). Els Wauters is supported by Stichting tegen Kanker (Mandate for basic & clinical oncology research). David E. Leaf is supported by NIH grants R01HL144566 and R01DK125786. Sandra M. Herrmann is supported by NIH grant K08 DK118120, the Mary Kathryn and Michael B. Panitch Career Development Award, and Mayo Clinic K2R award.
Keywords
- CTLA-4 antigen
- immunotherapy
- programmed cell death 1 receptor
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Molecular Medicine
- Oncology
- Pharmacology
- Cancer Research