TY - JOUR
T1 - Clinical features and outcomes of immune checkpoint inhibitor-associated AKI
T2 - A multicenter study
AU - Cortazar, Frank B.
AU - Kibbelaar, Zoe A.
AU - Glezerman, Ilya G.
AU - Abudayyeh, Ala
AU - Mamlouk, Omar
AU - Motwani, Shveta S.
AU - Murakami, Naoka
AU - Herrmann, Sandra M.
AU - Manohar, Sandhya
AU - Shirali, Anushree C.
AU - Kitchlu, Abhijat
AU - Shirazian, Shayan
AU - Assal, Amer
AU - Vijayan, Anitha
AU - Renaghan, Amanda De Mauro
AU - Ortiz-Melo, David I.
AU - Rangarajan, Sunil
AU - Malik, A. Bilal
AU - Hogan, Jonathan J.
AU - Dinh, Alex R.
AU - Shin, Daniel Sanghoon
AU - Marrone, Kristen A.
AU - Mithani, Zain
AU - Johnson, Douglas B.
AU - Hosseini, Afrooz
AU - Uprety, Deekchha
AU - Sharma, Shreyak
AU - Gupta, Shruti
AU - Reynolds, Kerry L.
AU - Sise, Meghan E.
AU - Leaf, David E.
N1 - Funding Information:
Dr. Glezerman is supported by the National Cancer Institute (grant P30CA008748). Dr. Murakami is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; grant K08DK120868) and an American Society of Nephrology (ASN) Foundation for Kidney Research Carl W. Gottschalk research scholar grant. Dr. Herrmann is supported by the NIDDK (grant K08DK118120). Dr. Sise is supported by the NIDDK (grant K23DK117014). Dr. Leaf is supported by the NIDDK (grant K23DK106448), the National Heart, Lung, and Blood Institute (grant R01HL144566), and an ASN Foundation for Kidney Research Carl W. Gottschalk research scholar grant.
Funding Information:
Dr. Assal reports grants from NIH/NCI Cancer Center, during the conduct of the study; personal fees from Alpha Insights, personal fees from Boston Biomedical, personal fees from Incyte Corporation, grants from Incyte Corporation, outside the submitted work. Dr. Glezerman reports other from Pfizer Inc., outside the submitted work. Dr. Gupta reports grants from NIH, during the conduct of the study. Dr. Johnson reports other from Array Biopharma, grants and other from BMS, grants and other from Incyte, other from Merck, other from Novartis, outside the submitted work. Dr. Leaf reports grants from BioPorto Diagnostics, outside the submitted work. Dr. Marrone reports other from AstraZeneca, other from Compugen, other from Takeda, outside the submitted work. Dr. Vijayan reports personal fees from Sanofi-Aventis, outside the submitted work. All other authors report no relevant disclosures.
Publisher Copyright:
© 2020 by the American Society of Nephrology.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2019070676
DO - 10.1681/ASN.2019070676
M3 - Article
C2 - 31896554
AN - SCOPUS:85078869729
SN - 1046-6673
VL - 31
SP - 435
EP - 446
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 2
ER -