Acute kidney injury in patients treated with immune checkpoint inhibitors

Shruti Gupta; Samuel A.P. Short; Meghan E. Sise; Jason M. Prosek; Sethu M. Madhavan; Maria Jose Soler; Marlies Ostermann; Sandra M. Herrmann; Ala Abudayyeh; Shuchi Anand; Ilya Glezerman; Shveta S. Motwani; Naoka Murakami; Rimda Wanchoo; David I. Ortiz-Melo; Arash Rashidi; Ben Sprangers; Vikram Aggarwal; A. Bilal Malik; Sebastian Loew; Christopher A. Carlos; Wei Ting Chang; Pazit Beckerman; Zain Mithani; Chintan V. Shah; Amanda D. Renaghan; Sophie De Seigneux; Luca Campedel; Abhijat Kitchlu; Daniel Sanghoon Shin; Sunil Rangarajan; Priya Deshpande; Gaia Coppock; Mark Eijgelsheim; Harish Seethapathy; Meghan D. Lee; Ian A. Strohbehn; Dwight H. Owen; Marium Husain; Clara Garcia-Carro; Sheila Bermejo; Nuttha Lumlertgul; Nina Seylanova; Lucy Flanders; Busra Isik; Omar Mamlouk; Jamie S. Lin; Pablo Garcia; Aydin Kaghazchi; Yuriy Khanin; Sheru K. Kansal; Els Wauters; Sunandana Chandra; Kai M. Schmidt-Ott; Raymond K. Hsu; Maria C. Tio; Suraj Sarvode Mothi; Harkarandeep Singh; Deborah Schrag; Kenar D. Jhaveri; Kerry L. Reynolds; Frank B. Cortazar; David E. Leaf

doi:10.1136/jitc-2021-003467

Acute kidney injury in patients treated with immune checkpoint inhibitors

Shruti Gupta^*, Samuel A.P. Short, Meghan E. Sise, Jason M. Prosek, Sethu M. Madhavan, Maria Jose Soler, Marlies Ostermann, Sandra M. Herrmann, Ala Abudayyeh, Shuchi Anand, Ilya Glezerman, Shveta S. Motwani, Naoka Murakami, Rimda Wanchoo, David I. Ortiz-Melo, Arash Rashidi, Ben Sprangers, Vikram Aggarwal, A. Bilal Malik, Sebastian LoewChristopher A. Carlos, Wei Ting Chang, Pazit Beckerman, Zain Mithani, Chintan V. Shah, Amanda D. Renaghan, Sophie De Seigneux, Luca Campedel, Abhijat Kitchlu, Daniel Sanghoon Shin, Sunil Rangarajan, Priya Deshpande, Gaia Coppock, Mark Eijgelsheim, Harish Seethapathy, Meghan D. Lee, Ian A. Strohbehn, Dwight H. Owen, Marium Husain, Clara Garcia-Carro, Sheila Bermejo, Nuttha Lumlertgul, Nina Seylanova, Lucy Flanders, Busra Isik, Omar Mamlouk, Jamie S. Lin, Pablo Garcia, Aydin Kaghazchi, Yuriy Khanin, Sheru K. Kansal, Els Wauters, Sunandana Chandra, Kai M. Schmidt-Ott, Raymond K. Hsu, Maria C. Tio, Suraj Sarvode Mothi, Harkarandeep Singh, Deborah Schrag, Kenar D. Jhaveri, Kerry L. Reynolds, Frank B. Cortazar, David E. Leaf

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

146 Scopus citations

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.

Original language	English (US)
Article number	e003467
Journal	Journal for immunotherapy of cancer
Volume	9
Issue number	10
DOIs	https://doi.org/10.1136/jitc-2021-003467
State	Published - Oct 8 2021

Funding

Disclaimer Shruti Gupta is a Scientific Coordinator for GlaxoSmithKline’s ASCEND Trial and receives funding from GE Healthcare. Sunil Rangarajan is supported by the 2020 Young Investigator Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology and by the UAB-UCSD O'Brien Center for Acute Kidney Injury Research (NIH P30-DK079337). Kenar D. Jhaveri is a consultant for Astex Pharmaceuticals, Natera, GlaxoSmithKline, ChemoCentryx, and Chinook, a paid contributor to Uptodate.com, and receives honorarium from ISN and ASN. Daniel Sanghoon Shin participates in the speakers’ bureau at Genentech. Sunandana Chandra is on the Advisory Board or Bristol Myers Squibb, EMD Serono, Regeneron, Sanofi Genzyme, Exicure, Pfizer, and Novartis, and on the steering committee for Genentech. Shveta S. Motwani is a Deputy Editor at UpToDate. Naoka Murakami reports funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; K08DK12068) and from the American Society of Nephrology (Carl W. Gottschalk Research Scholar Grant). Frank B. Cortazar is a consultant for ChemoCentryx and Retrophin. Maria J. Soler reports personal fees from NovoNordisk, Jansen, Mundipharma, AstraZeneca, Esteve, Fresenius, Ingelheim Lilly, Vifor, ICU and grants and personal fees from Boehringer. Clara García-Carro has given scientific lectures and participated in advisory boards organized by Astra-Zeneca, Boehringer-Ingelheim Lilly, Mundipharma and NovoNordisk. Ala Abudayyeh and Jamie S. Lin are supported by the Division of Internal Medicine Immuno-Oncology Toxicity Award Program of the University of Texas MD Anderson Cancer Center. Jamie S. Lin is supported by a grant from the National Institutes of Health (NIH; K08DK119466). Ben Sprangers is a senior clinical investigator at the Research Foundation Flanders (F.W.O.) (1842919N) and is supported by Stichting tegen Kanker (grant C/2020/1380). Arash Rashidi is a consultant for Otsuka pharmaceutical company. Ilya Glezerman’s spouse has stock ownership in Pfizer. Sethu M. Madhavan is supported by NIH grant K08 DK123411. Dwight H. Owen is a Paul Calabresi Scholar supported by the OSU K12 Training Grant for Clinical Faculty Investigators (K12 CA133250) and reports research support (to institution) from Bristol Myers Squibb, Merck, Palobiofarma, Genentech. Dr. Owen is also supported in part by The Ohio State University Comprehensive Cancer Center and by the NIH (P30 CA016058). Els Wauters is supported by Stichting tegen Kanker (Mandate for basic & clinical oncology research). David E. Leaf is supported by NIH grants R01HL144566 and R01DK125786. Sandra M. Herrmann is supported by NIH grant K08 DK118120, the Mary Kathryn and Michael B. Panitch Career Development Award, and Mayo Clinic K2R award.

Keywords

CTLA-4 antigen
immunotherapy
programmed cell death 1 receptor

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Molecular Medicine
Oncology
Pharmacology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/jitc-2021-003467

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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., ... Leaf, D. E. (2021). Acute kidney injury in patients treated with immune checkpoint inhibitors. Journal for immunotherapy of cancer, 9(10), Article e003467. https://doi.org/10.1136/jitc-2021-003467

@article{dbe7f5b824f94695b8c1fd9cfce4f3ec,

title = "Acute kidney injury in patients treated with immune checkpoint inhibitors",

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 = "CTLA-4 antigen, immunotherapy, programmed cell death 1 receptor",

author = "Shruti Gupta and Short, {Samuel A.P.} and Sise, {Meghan E.} and Prosek, {Jason M.} and Madhavan, {Sethu M.} and Soler, {Maria Jose} and Marlies Ostermann and Herrmann, {Sandra M.} and Ala Abudayyeh and Shuchi Anand and Ilya Glezerman and Motwani, {Shveta S.} and Naoka Murakami and Rimda Wanchoo and Ortiz-Melo, {David I.} and Arash Rashidi and Ben Sprangers and Vikram Aggarwal and Malik, {A. Bilal} and Sebastian Loew and Carlos, {Christopher A.} and Chang, {Wei Ting} and Pazit Beckerman and Zain Mithani and Shah, {Chintan V.} and Renaghan, {Amanda D.} and Seigneux, {Sophie De} and Luca Campedel and Abhijat Kitchlu and Shin, {Daniel Sanghoon} and Sunil Rangarajan and Priya Deshpande and Gaia Coppock and Mark Eijgelsheim and Harish Seethapathy and Lee, {Meghan D.} and Strohbehn, {Ian A.} and Owen, {Dwight H.} and Marium Husain and Clara Garcia-Carro and Sheila Bermejo and Nuttha Lumlertgul and Nina Seylanova and Lucy Flanders and Busra Isik and Omar Mamlouk and Lin, {Jamie S.} and Pablo Garcia and Aydin Kaghazchi and Yuriy Khanin and Kansal, {Sheru K.} and Els Wauters and Sunandana Chandra and Schmidt-Ott, {Kai M.} and Hsu, {Raymond K.} and Tio, {Maria C.} and {Sarvode Mothi}, Suraj and Harkarandeep Singh and Deborah Schrag and Jhaveri, {Kenar D.} and Reynolds, {Kerry L.} and Cortazar, {Frank B.} and Leaf, {David E.}",

note = "Publisher Copyright: {\textcopyright} ",

year = "2021",

month = oct,

day = "8",

doi = "10.1136/jitc-2021-003467",

language = "English (US)",

volume = "9",

journal = "Journal for immunotherapy of cancer",

issn = "2051-1426",

publisher = "BMJ Publishing Group",

number = "10",

}

Gupta, S, Short, SAP, Sise, ME, Prosek, JM, Madhavan, SM, Soler, MJ, Ostermann, M, Herrmann, SM, Abudayyeh, A, Anand, S, Glezerman, I, Motwani, SS, Murakami, N, Wanchoo, R, Ortiz-Melo, DI, Rashidi, A, Sprangers, B, Aggarwal, V, Malik, AB, Loew, S, Carlos, CA, Chang, WT, Beckerman, P, Mithani, Z, Shah, CV, Renaghan, AD, Seigneux, SD, Campedel, L, Kitchlu, A, Shin, DS, Rangarajan, S, Deshpande, P, Coppock, G, Eijgelsheim, M, Seethapathy, H, Lee, MD, Strohbehn, IA, Owen, DH, Husain, M, Garcia-Carro, C, Bermejo, S, Lumlertgul, N, Seylanova, N, Flanders, L, Isik, B, Mamlouk, O, Lin, JS, Garcia, P, Kaghazchi, A, Khanin, Y, Kansal, SK, Wauters, E, Chandra, S, Schmidt-Ott, KM, Hsu, RK, Tio, MC, Sarvode Mothi, S, Singh, H, Schrag, D, Jhaveri, KD, Reynolds, KL, Cortazar, FB & Leaf, DE 2021, 'Acute kidney injury in patients treated with immune checkpoint inhibitors', Journal for immunotherapy of cancer, vol. 9, no. 10, e003467. https://doi.org/10.1136/jitc-2021-003467

TY - JOUR

T1 - Acute kidney injury in patients treated with immune checkpoint inhibitors

AU - Gupta, Shruti

AU - Short, Samuel A.P.

AU - Sise, Meghan E.

AU - Prosek, Jason M.

AU - Madhavan, Sethu M.

AU - Soler, Maria Jose

AU - Ostermann, Marlies

AU - Herrmann, Sandra M.

AU - Abudayyeh, Ala

AU - Anand, Shuchi

AU - Glezerman, Ilya

AU - Motwani, Shveta S.

AU - Murakami, Naoka

AU - Wanchoo, Rimda

AU - Ortiz-Melo, David I.

AU - Rashidi, Arash

AU - Sprangers, Ben

AU - Aggarwal, Vikram

AU - Malik, A. Bilal

AU - Loew, Sebastian

AU - Carlos, Christopher A.

AU - Chang, Wei Ting

AU - Beckerman, Pazit

AU - Mithani, Zain

AU - Shah, Chintan V.

AU - Renaghan, Amanda D.

AU - Seigneux, Sophie De

AU - Campedel, Luca

AU - Kitchlu, Abhijat

AU - Shin, Daniel Sanghoon

AU - Rangarajan, Sunil

AU - Deshpande, Priya

AU - Coppock, Gaia

AU - Eijgelsheim, Mark

AU - Seethapathy, Harish

AU - Lee, Meghan D.

AU - Strohbehn, Ian A.

AU - Owen, Dwight H.

AU - Husain, Marium

AU - Garcia-Carro, Clara

AU - Bermejo, Sheila

AU - Lumlertgul, Nuttha

AU - Seylanova, Nina

AU - Flanders, Lucy

AU - Isik, Busra

AU - Mamlouk, Omar

AU - Lin, Jamie S.

AU - Garcia, Pablo

AU - Kaghazchi, Aydin

AU - Khanin, Yuriy

AU - Kansal, Sheru K.

AU - Wauters, Els

AU - Chandra, Sunandana

AU - Schmidt-Ott, Kai M.

AU - Hsu, Raymond K.

AU - Tio, Maria C.

AU - Sarvode Mothi, Suraj

AU - Singh, Harkarandeep

AU - Schrag, Deborah

AU - Jhaveri, Kenar D.

AU - Reynolds, Kerry L.

AU - Cortazar, Frank B.

AU - Leaf, David E.

PY - 2021/10/8

Y1 - 2021/10/8

N2 - 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.

AB - 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.

KW - CTLA-4 antigen

KW - immunotherapy

KW - programmed cell death 1 receptor

UR - http://www.scopus.com/inward/record.url?scp=85117119125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85117119125&partnerID=8YFLogxK

U2 - 10.1136/jitc-2021-003467

DO - 10.1136/jitc-2021-003467

M3 - Article

C2 - 34625513

AN - SCOPUS:85117119125

SN - 2051-1426

VL - 9

JO - Journal for immunotherapy of cancer

JF - Journal for immunotherapy of cancer

IS - 10

M1 - e003467

ER -

Acute kidney injury in patients treated with immune checkpoint inhibitors

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