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


Authors: 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.; Ortiz-Melo, D. I.; Rangarajan, S.; Malik, A. B.; Hogan, J. J.; Dinh, A. R.; Shin, D. S.; Marrone, K. A.; Mithani, Z.; Johnson, D. B.; Hosseini, A.; Uprety, D.; Sharma, S.; Gupta, S.; Reynolds, K. L.; Sise, M. E.; Leaf, D. E.
Article Title: Clinical features and outcomes of immune checkpoint inhibitor-associated AKI: A multicenter study
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. © 2020 by the American Society of Nephrology.
Keywords: adult; controlled study; aged; antibiotic agent; unclassified drug; major clinical study; overall survival; prednisone; clinical feature; mortality; hepatitis; rituximab; antineoplastic agent; melanoma; nephrotoxicity; cohort analysis; lung cancer; creatinine; cyclophosphamide; steroid; creatinine blood level; retrospective study; hematuria; pneumonia; rash; acute kidney failure; disease severity; nonsteroid antiinflammatory agent; proton pump inhibitor; glucocorticoid; colitis; corticosteroid; immunosuppressive treatment; kidney biopsy; proteinuria; immunosuppressive agent; eculizumab; thyroid disease; hypophysitis; eosinophilia; methylprednisolone sodium succinate; immune checkpoint inhibitor; renal replacement therapy; pyuria; mycophenolate mofetil; prognosis; human; male; female; priority journal; article; urine sediment; interstitial nephritis; immunological antineoplastic agent; glomerulus basement membrane
Journal Title: Journal of the American Society of Nephrology
Volume: 31
Issue: 2
ISSN: 1046-6673
Publisher: American Society of Nephrology  
Date Published: 2020-02-01
Start Page: 435
End Page: 446
Language: English
DOI: 10.1681/asn.2019070676
PUBMED: 31896554
PROVIDER: scopus
PMCID: PMC7003302
DOI/URL:
Notes: Article -- Export Date: 2 March 2020 -- Source: Scopus
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