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Acute kidney injury in patients treated with immune checkpoint inhibitors

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Item Type:Article
Title:Acute kidney injury in patients treated with immune checkpoint inhibitors
Creators Name:Gupta, S. and Short, S.A.P. and Sise, M.E. and Prosek, J.M. and Madhavan, S.M. and Soler, M.J. and Ostermann, M. and Herrmann, S.M. and Abudayyeh, A. and Anand, S. and Glezerman, I. and Motwani, S.S. and Murakami, N. and Wanchoo, R. and Ortiz-Melo, D.I. and Rashidi, A. and Sprangers, B. and Aggarwal, V. and Malik, A.B. and Loew, S. and Carlos, C.A. and Chang, W.T. and Beckerman, P. and Mithani, Z. and Shah, C.V. and Renaghan, A.D. and Seigneux, S.D. and Campedel, L. and Kitchlu, A. and Shin, D.S. and Rangarajan, S. and Deshpande, P. and Coppock, G. and Eijgelsheim, M. and Seethapathy, H. and Lee, M.D. and Strohbehn, I.A. and Owen, D.H. and Husain, M. and Garcia-Carro, C. and Bermejo, S. and Lumlertgul, N. and Seylanova, N. and Flanders, L. and Isik, B. and Mamlouk, O. and Lin, J.S. and Garcia, P. and Kaghazchi, A. and Khanin, Y. and Kansal, S.K. and Wauters, E. and Chandra, S. and Schmidt-Ott, K.M. and Hsu, R.K. and Tio, M.C. and Sarvode Mothi, S. and Singh, H. and Schrag, D. and Jhaveri, K.D. and Reynolds, K.L. and Cortazar, F.B. and Leaf, D.E.
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.
Keywords:Acute Kidney Injury, Cohort Studies, Immune Checkpoint Inhibitors, Immunotherapy, Risk Factors
Source:Journal for ImmunoTherapy of Cancer
Publisher:BMJ Publishing Group
Page Range:e003467
Date:October 2021
Official Publication:https://doi.org/10.1136/jitc-2021-003467
PubMed:View item in PubMed

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