Journal for ImmunoTherapy of Cancer (Oct 2021)

Acute kidney injury in patients treated with immune checkpoint inhibitors

  • ,
  • Joe-Elie Salem,
  • Enriqueta Felip,
  • Sophie Papa,
  • Shuchi Anand,
  • Karolina Benesova,
  • Marlies Ostermann,
  • Ala Abudayyeh,
  • Omar Mamlouk,
  • Umut Selamet,
  • Grace Cherry,
  • Sunandana Chandra,
  • Sandra M Herrmann,
  • Maria Jose Soler,
  • Abhijat Kitchlu,
  • Jamie S Lin,
  • Kerry L Reynolds,
  • Osama E Rahma,
  • Elizabeth M Gaughan,
  • Eva Muñoz-Couselo,
  • Jamie S Hirsch,
  • Pablo Garcia,
  • Meghan D Lee,
  • Harish Seethapathy,
  • Ian A Strohbehn,
  • Meghan E Sise,
  • Wei-Ting Chang,
  • Els Wauters,
  • Lucy Flanders,
  • Deborah Schrag,
  • Thibaud Koessler,
  • Mark Eijgelsheim,
  • Shruti Gupta,
  • Frank B Cortazar,
  • Samuel A P Short,
  • Jason M Prosek,
  • Sethu M Madhavan,
  • Ilya Glezerman,
  • Shveta S Motwani,
  • Naoka Murakami,
  • Rimda Wanchoo,
  • David I Ortiz-Melo,
  • Arash Rashidi,
  • Ben Sprangers,
  • Vikram Aggarwal,
  • A Bilal Malik,
  • Sebastian Loew,
  • Christopher A Carlos,
  • Pazit Beckerman,
  • Zain Mithani,
  • Chintan V Shah,
  • Amanda D Renaghan,
  • Sophie De Seigneux,
  • Luca Campedel,
  • Daniel Sanghoon Shin,
  • Sunil Rangarajan,
  • Priya Deshpande,
  • Gaia Coppock,
  • Dwight H. Owen,
  • Marium Husain,
  • Clara Garcia-Carro,
  • Sheila Bermejo,
  • Nuttha Lumlertgul,
  • Nina Seylanova,
  • Busra Isik,
  • Aydin Kaghazchi,
  • Yuriy Khanin,
  • Sheru K Kansal,
  • Kai M Schmidt-Ott,
  • Raymond K Hsu,
  • Maria C Tio,
  • Suraj Sarvode Mothi,
  • Harkarandeep Singh,
  • Kenar D Jhaveri,
  • David E Leaf,
  • Corinne Isnard Bagnis,
  • Suraj S Mothi,
  • Weiting Chang,
  • Vipulbhai Sakhiya,
  • Daniel Stalbow,
  • Sylvia Wu,
  • Armando Cennamo,
  • Anne Rigg,
  • Nisha Shaunak,
  • Zoe A Kibbelaar,
  • Harish S Seethapathy,
  • Meghan Lee,
  • Ian A Strohbhen,
  • Ilya G Glezerman,
  • Dwight H Owen,
  • Sharon Mini,
  • Andrey Kisel,
  • Nicole Albert,
  • Katherine Carter,
  • Vicki Donley,
  • Tricia Young,
  • Heather Cigoi,
  • Els Wauters Ben Sprangers,
  • Javier A Pagan,
  • Jonathan J Hogan,
  • Valda Page,
  • Samuel AP Short,
  • A Bilal Malik,
  • Maria Josep Carreras

DOI
https://doi.org/10.1136/jitc-2021-003467
Journal volume & issue
Vol. 9, no. 10

Abstract

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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.