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 |
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Article number | e003467 |
Journal | Journal for ImmunoTherapy of Cancer |
Volume | 9 |
Issue number | 10 |
DOIs | |
State | Published - 8 Oct 2021 |
Funding
Funders | Funder number |
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Division of Internal Medicine | |
F.W.O. | 1842919N |
Ohio State University Comprehensive Cancer Center | P30 CA016058, K08 DK118120, R01HL144566 |
National Institutes of Health | |
National Cancer Institute | K12CA133250 |
National Institute of Diabetes and Digestive and Kidney Diseases | K08DK12068, R01DK125786, K08DK119466 |
Mayo Clinic | |
Conquer Cancer Foundation | |
American Society of Nephrology | |
Bristol-Myers Squibb | |
Merck | |
American Society of Clinical Oncology | P30-DK079337 |
GE Healthcare | |
Ohio State University | K12 CA133250 |
University of Texas MD Anderson Cancer Center | |
Fonds Wetenschappelijk Onderzoek | |
Stichting Tegen Kanker | K08 DK123411, C/2020/1380 |
Keywords
- CTLA-4 antigen
- immunotherapy
- programmed cell death 1 receptor