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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., Short, S.A.P., Sise, M.E., Prosek, J.M., Madhavan, S.M., Soler, M.J., Ostermann, M., Herrmann, S.M., Abudayyeh, A., Anand, S., Glezerman, I., Motwani, S.S., Murakami, N., Wanchoo, R., Ortiz-Melo, D.I., Rashidi, A., Sprangers, B., Aggarwal, V., Malik, A.B., Loew, S., Carlos, C.A., Chang, W.T., Beckerman, P., Mithani, Z., Shah, C.V., Renaghan, A.D., Seigneux, S.D., Campedel, L., Kitchlu, A., Shin, D.S., Rangarajan, S., Deshpande, P., Coppock, G., Eijgelsheim, M., Seethapathy, H., Lee, M.D., Strohbehn, I.A., Owen, D.H., Husain, M., Garcia-Carro, C., Bermejo, S., Lumlertgul, N., Seylanova, N., Flanders, L., Isik, B., Mamlouk, O., Lin, J.S., Garcia, P., Kaghazchi, A., Khanin, Y., Kansal, S.K., Wauters, E., Chandra, S., Schmidt-Ott, K.M., Hsu, R.K., Tio, M.C., Sarvode Mothi, S., Singh, H., Schrag, D., Jhaveri, K.D., Reynolds, K.L., 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
ISSN:2051-1426
Publisher:BMJ Publishing Group
Volume:9
Number:10
Page Range:e003467
Date:October 2021
Additional Information:Erratum in: J Immunother Cancer ;11:e003467corr1
Official Publication:https://doi.org/10.1136/jitc-2021-003467
PubMed:View item in PubMed

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