Clinical features and outcomes of immune checkpoint inhibitor-associated AKI: A multicenter study

Frank B. Cortazar, Zoe A. Kibbelaar, Ilya G. Glezerman, Ala Abudayyeh, Omar Mamlouk, Shveta S. Motwani, Naoka Murakami, Sandra M. Herrmann, Sandhya Manohar, Anushree C. Shirali, Abhijat Kitchlu, Shayan Shirazian, Amer Assal, Anitha Vijayan, Amanda De Mauro Renaghan, David I. Ortiz-Melo, Sunil Rangarajan, A. Bilal Malik, Jonathan J. Hogan, Alex R. DinhDaniel Sanghoon Shin, Kristen A. Marrone, Zain Mithani, Douglas B. Johnson, Afrooz Hosseini, Deekchha Uprety, Shreyak Sharma, Shruti Gupta, Kerry L. Reynolds, Meghan E. Sise, David E. Leaf

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

BackgroundDespite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. MethodsWe conducted amulticenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a$2-fold increase in serumcreatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor.Wealso collected data on 276 control patientswho received these drugs but did not develop AKI. Results Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor- associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. Conclusions Thismulticenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.

Original languageEnglish
Pages (from-to)435-446
Number of pages12
JournalJournal of the American Society of Nephrology
Volume31
Issue number2
DOIs
StatePublished - Jan 1 2020

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    Cortazar, F. B., Kibbelaar, Z. A., Glezerman, I. G., Abudayyeh, A., Mamlouk, O., Motwani, S. S., Murakami, N., Herrmann, S. M., Manohar, S., Shirali, A. C., Kitchlu, A., Shirazian, S., Assal, A., Vijayan, A., Renaghan, A. D. M., Ortiz-Melo, D. I., Rangarajan, S., Malik, A. B., Hogan, J. J., ... Leaf, D. E. (2020). Clinical features and outcomes of immune checkpoint inhibitor-associated AKI: A multicenter study. Journal of the American Society of Nephrology, 31(2), 435-446. https://doi.org/10.1681/ASN.2019070676