학술논문
Acute kidney injury in patients treated with immune checkpoint inhibitors
Document Type
article
Author
Gupta, Shruti; Short, Samuel AP; Sise, Meghan E; Prosek, Jason M; Madhavan, Sethu M; Soler, Maria Jose; Ostermann, Marlies; Herrmann, Sandra M; Abudayyeh, Ala; Anand, Shuchi; Glezerman, Ilya; Motwani, Shveta S; Murakami, Naoka; Wanchoo, Rimda; Ortiz-Melo, David I; Rashidi, Arash; Sprangers, Ben; Aggarwal, Vikram; Malik, A Bilal; Loew, Sebastian; Carlos, Christopher A; Chang, Wei-Ting; Beckerman, Pazit; Mithani, Zain; Shah, Chintan V; Renaghan, Amanda D; De Seigneux, Sophie; Campedel, Luca; Kitchlu, Abhijat; Shin, Daniel Sanghoon; Rangarajan, Sunil; Deshpande, Priya; Coppock, Gaia; Eijgelsheim, Mark; Seethapathy, Harish; Lee, Meghan D; Strohbehn, Ian A; Owen, Dwight H; Husain, Marium; Garcia-Carro, Clara; Bermejo, Sheila; Lumlertgul, Nuttha; Seylanova, Nina; Flanders, Lucy; Isik, Busra; Mamlouk, Omar; Lin, Jamie S; Garcia, Pablo; Kaghazchi, Aydin; Khanin, Yuriy; Kansal, Sheru K; Wauters, Els; Chandra, Sunandana; Schmidt-Ott, Kai M; Hsu, Raymond K; Tio, Maria C; Mothi, Suraj Sarvode; Singh, Harkarandeep; Schrag, Deborah; Jhaveri, Kenar D; Reynolds, Kerry L; Cortazar, Frank B; Leaf, David E; Salem, Joe-Elie; Bagnis, Corinne Isnard; Rahma, Osama E; Mothi, Suraj S; Selamet, Umut; Chang, Weiting; Hirsch, Jamie S; Sakhiya, Vipulbhai; Stalbow, Daniel; Wu, Sylvia; Cennamo, Armando; Papa, Sophie; Rigg, Anne; Shaunak, Nisha; Kibbelaar, Zoe A; Benesova, Karolina
Source
Journal for ImmunoTherapy of Cancer. 9(10)
Subject
Language
Abstract
BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe 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.ResultsICPi-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.ConclusionsPatients 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.