Acute kidney injury in patients treated with immune checkpoint inhibitors

Shruti Gupta*, Samuel A.P. Short, Meghan E. Sise, Jason M. Prosek, Sethu M. Madhavan, Maria Jose Soler, Marlies Ostermann, Sandra M. Herrmann, Ala Abudayyeh, Shuchi Anand, Ilya Glezerman, Shveta S. Motwani, Naoka Murakami, Rimda Wanchoo, David I. Ortiz-Melo, Arash Rashidi, Ben Sprangers, Vikram Aggarwal, A. Bilal Malik, Sebastian LoewChristopher A. Carlos, Wei Ting Chang, Pazit Beckerman, Zain Mithani, Chintan V. Shah, Amanda D. Renaghan, Sophie De Seigneux, Luca Campedel, Abhijat Kitchlu, Daniel Sanghoon Shin, Sunil Rangarajan, Priya Deshpande, Gaia Coppock, Mark Eijgelsheim, Harish Seethapathy, Meghan D. Lee, Ian A. Strohbehn, Dwight H. Owen, Marium Husain, Clara Garcia-Carro, Sheila Bermejo, Nuttha Lumlertgul, Nina Seylanova, Lucy Flanders, Busra Isik, Omar Mamlouk, Jamie S. Lin, Pablo Garcia, Aydin Kaghazchi, Yuriy Khanin, Sheru K. Kansal, Els Wauters, Sunandana Chandra, Kai M. Schmidt-Ott, Raymond K. Hsu, Maria C. Tio, Suraj Sarvode Mothi, Harkarandeep Singh, Deborah Schrag, Kenar D. Jhaveri, Kerry L. Reynolds, Frank B. Cortazar, David E. Leaf

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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 languageEnglish (US)
Article numbere003467
JournalJournal for immunotherapy of cancer
Volume9
Issue number10
DOIs
StatePublished - Oct 8 2021

Keywords

  • CTLA-4 antigen
  • immunotherapy
  • programmed cell death 1 receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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