Multicenter Study

. 2022 Sep;10(9):e005646.

doi: 10.1136/jitc-2022-005646.

Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI

Shruti Gupta¹, Clara Garcia-Carro², Jason M Prosek³, Ilya Glezerman⁴, Sandra M Herrmann⁵, Pablo Garcia⁶, Ala Abudayyeh⁷, Nuttha Lumlertgul^{8

9}, A Bilal Malik¹⁰, Sebastian Loew¹¹, Pazit Beckerman¹², Amanda D Renaghan¹³, Christopher A Carlos¹⁴, Arash Rashidi¹⁵, Zain Mithani¹⁶, Priya Deshpande¹⁷, Sunil Rangarajan¹⁸, Chintan V Shah¹⁹, Sophie De Seigneux²⁰, Luca Campedel²¹, Abhijat Kitchlu²², Daniel Sanghoon Shin²³, Gaia Coppock²⁴, David I Ortiz-Melo²⁵, Ben Sprangers^{26

27}, Vikram Aggarwal²⁸, Karolina Benesova²⁹, Rimda Wanchoo³⁰, Naoka Murakami³¹, Frank B Cortazar³², Kerry L Reynolds³³, Meghan E Sise^#³⁴, Maria Jose Soler^#³⁵, David E Leaf^#³¹; ICPi-AKI Consortium Investigators

Collaborators, Affiliations

Collaborators

ICPi-AKI Consortium Investigators:
Luca Campedel, Joe-Elie Salem, Corinne Isnard Bagnis, Shruti Gupta, David E Leaf, Harkarandeep Singh, Shveta S Motwani, Naoka Murakami, Maria C Tio, Suraj S Mothi, Umut Selamet, Sebastian Loew, Kai M Schmidt-Ott, Weiting Chang, Kenar D Jhaveri, Rimda Wanchoo, Yuriy Khanin, Jamie S Hirsch, Vipulbhai Sakhiya, Daniel Stalbow, Sylvia Wu, David I Ortiz-Melo, Marlies Ostermann, Nuttha Lumlertgul, Nina Seylanova, Armando Cennamo, Anne Rigg, Nisha Shaunak, Zoe A Kibbelaar, Karolina Benesova, Priya Deshpande, Meghan E Sise, Kerry L Reynolds, Harish S Seethapathy, Meghan Lee, Ian A Strohbhen, Sandra M Herrmann, Busra Isik, Ilya G Glezerman, Frank B Cortazar, Vikram Aggarwal, Sunandana Chandra, Jason M Prosek, Sethu M Madhavan, Dwight H Owen, Marium Husain, Pazit Beckerman, Sharon Mini, Shuchi Anand, Pablo Garcia, Aydin Kaghazchi, Sunil Rangarajan, Daniel Sanghoon Shin, Grace Cherry, Christopher A Carlos, Raymond K Hsu, Andrey Kisel, Arash Rashidi, Sheru K Kansal, Nicole Albert, Katherine Carter, Vicki Donley, Tricia Young, Heather Cigoi, Sophie De Seigneux, Thibaud Koessler, Els Wauters Ben Sprangers, Chintan V Shah, Mark Eijgelsheim, Zain Mithani, Javier A Pagan, Gaia Coppock, Jonathan J Hogan, Ala Abudayyeh, Omar Mamlouk, Jamie S Lin, Valda Page, Abhijat Kitchlu, Samuel Ap Short, Amanda D Renaghan, Elizabeth M Gaughan, A Bilal Malik, Maria Jose Soler, Clara García-Carro, Sheila Bermejo, Enriqueta Felip, Eva Muñoz-Couselo, Maria Josep Carreras

Affiliations

¹ Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA sgupta21@bwh.harvard.edu.
² Nephrology Department, San Carlos Clinical University Hospital, Madrid, Spain.
³ Division of Nephrology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
⁴ Renal Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.
⁵ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA, USA.
⁷ Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Critical Care, Guy's and St Thomas' Hospitals NHS Trust, London, UK.
⁹ Division of Nephrology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
¹⁰ Division of Nephrology, University of Washington, Seattle, Washington, USA.
¹¹ Department of Nephrology and Medical Intensive Care, Charite Universitatsmedizin Berlin, Berlin, Germany.
¹² Institute of Nephrology and Hypertension, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹³ Division of Nephrology, University of Virginia Health System, Charlottesville, Virginia, USA.
¹⁴ Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
¹⁵ Division of Nephrology and Hypertension, University Hospital Cleveland Medical Center, Cleveland, Ohio, USA.
¹⁶ University of Miami Miller School of Medicine, Miami, Florida, USA.
¹⁷ Division of Nephrology, Department of Medicine, Icahn School of Medicine at the Mount Sinai Hospital, New York, NY, USA.
¹⁸ Division of Hematology/Oncology and Division of Nephrology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
¹⁹ Division of Nephrology, Hypertension, and Renal Transplant, Department of Medicine, University of Florida, Gainesville, Florida, USA.
²⁰ Service of Nephrology, Department of Medicine, University Hospitals of Geneva, Geneve, Switzerland.
²¹ Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne Université, Hôpital Pitié-Salpêtrière, Institut universitaire de cancérologie, CLIP Galilée, Groupe de Recherche Interdisciplinaire Francophone en Onco-néphrologie (GRIFON), Paris, France.
²² Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
²³ Division of Hematology-Oncology, VAGLAHS, Department of Medicine, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA.
²⁴ Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁵ Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA.
²⁶ Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, Belgium.
²⁷ Division of Nephrology, University Hospitals Leuven, Leuven, Belgium.
²⁸ Department of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
²⁹ Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
³⁰ Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.
³¹ Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
³² New York Nephrology Vasculitis and Glomerular Center, Albany, New York, USA.
³³ Division of Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁴ Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁵ Nephrology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, Barcelona, Spain.

^# Contributed equally.

PMID: 36137651
PMCID: PMC9511654
DOI: 10.1136/jitc-2022-005646

Multicenter Study

Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI

Shruti Gupta et al. J Immunother Cancer. 2022 Sep.

. 2022 Sep;10(9):e005646.

doi: 10.1136/jitc-2022-005646.

Authors

Collaborators

ICPi-AKI Consortium Investigators:
Luca Campedel, Joe-Elie Salem, Corinne Isnard Bagnis, Shruti Gupta, David E Leaf, Harkarandeep Singh, Shveta S Motwani, Naoka Murakami, Maria C Tio, Suraj S Mothi, Umut Selamet, Sebastian Loew, Kai M Schmidt-Ott, Weiting Chang, Kenar D Jhaveri, Rimda Wanchoo, Yuriy Khanin, Jamie S Hirsch, Vipulbhai Sakhiya, Daniel Stalbow, Sylvia Wu, David I Ortiz-Melo, Marlies Ostermann, Nuttha Lumlertgul, Nina Seylanova, Armando Cennamo, Anne Rigg, Nisha Shaunak, Zoe A Kibbelaar, Karolina Benesova, Priya Deshpande, Meghan E Sise, Kerry L Reynolds, Harish S Seethapathy, Meghan Lee, Ian A Strohbhen, Sandra M Herrmann, Busra Isik, Ilya G Glezerman, Frank B Cortazar, Vikram Aggarwal, Sunandana Chandra, Jason M Prosek, Sethu M Madhavan, Dwight H Owen, Marium Husain, Pazit Beckerman, Sharon Mini, Shuchi Anand, Pablo Garcia, Aydin Kaghazchi, Sunil Rangarajan, Daniel Sanghoon Shin, Grace Cherry, Christopher A Carlos, Raymond K Hsu, Andrey Kisel, Arash Rashidi, Sheru K Kansal, Nicole Albert, Katherine Carter, Vicki Donley, Tricia Young, Heather Cigoi, Sophie De Seigneux, Thibaud Koessler, Els Wauters Ben Sprangers, Chintan V Shah, Mark Eijgelsheim, Zain Mithani, Javier A Pagan, Gaia Coppock, Jonathan J Hogan, Ala Abudayyeh, Omar Mamlouk, Jamie S Lin, Valda Page, Abhijat Kitchlu, Samuel Ap Short, Amanda D Renaghan, Elizabeth M Gaughan, A Bilal Malik, Maria Jose Soler, Clara García-Carro, Sheila Bermejo, Enriqueta Felip, Eva Muñoz-Couselo, Maria Josep Carreras

Affiliations

¹ Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA sgupta21@bwh.harvard.edu.
² Nephrology Department, San Carlos Clinical University Hospital, Madrid, Spain.
³ Division of Nephrology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
⁴ Renal Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.
⁵ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA, USA.
⁷ Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Critical Care, Guy's and St Thomas' Hospitals NHS Trust, London, UK.
⁹ Division of Nephrology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
¹⁰ Division of Nephrology, University of Washington, Seattle, Washington, USA.
¹¹ Department of Nephrology and Medical Intensive Care, Charite Universitatsmedizin Berlin, Berlin, Germany.
¹² Institute of Nephrology and Hypertension, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹³ Division of Nephrology, University of Virginia Health System, Charlottesville, Virginia, USA.
¹⁴ Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
¹⁵ Division of Nephrology and Hypertension, University Hospital Cleveland Medical Center, Cleveland, Ohio, USA.
¹⁶ University of Miami Miller School of Medicine, Miami, Florida, USA.
¹⁷ Division of Nephrology, Department of Medicine, Icahn School of Medicine at the Mount Sinai Hospital, New York, NY, USA.
¹⁸ Division of Hematology/Oncology and Division of Nephrology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
¹⁹ Division of Nephrology, Hypertension, and Renal Transplant, Department of Medicine, University of Florida, Gainesville, Florida, USA.
²⁰ Service of Nephrology, Department of Medicine, University Hospitals of Geneva, Geneve, Switzerland.
²¹ Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne Université, Hôpital Pitié-Salpêtrière, Institut universitaire de cancérologie, CLIP Galilée, Groupe de Recherche Interdisciplinaire Francophone en Onco-néphrologie (GRIFON), Paris, France.
²² Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
²³ Division of Hematology-Oncology, VAGLAHS, Department of Medicine, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA.
²⁴ Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁵ Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA.
²⁶ Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, Belgium.
²⁷ Division of Nephrology, University Hospitals Leuven, Leuven, Belgium.
²⁸ Department of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
²⁹ Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
³⁰ Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.
³¹ Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
³² New York Nephrology Vasculitis and Glomerular Center, Albany, New York, USA.
³³ Division of Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁴ Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁵ Nephrology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, Barcelona, Spain.

^# Contributed equally.

PMID: 36137651
PMCID: PMC9511654
DOI: 10.1136/jitc-2022-005646

Abstract

Background: Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration.

Methods: We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29-84 days).

Results: Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively).

Conclusion: A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.

Keywords: Immunotherapy.

PubMed Disclaimer

Conflict of interest statement

Competing interests: SG receives research funding from GE Healthcare and BTG International and is President and Founder of the American Society of Onconephrology. CGC has received travel and congress fees support from AstraZeneca, Esteve, NovoNordisk, Boehringer Ingelheim Lilly, Astellas, Otsuka, Novartis, Astellas, and Baxter and has given scientific lectures and participated in advisory boards organized by AstraZeneca, Boehringer Ingelheim Lilly, Mundipharma, and NovoNordisk. DSS participates in the speakers’ bureau at Genentech. FBC is a consultant for ChemoCentryx and Retrophin. AA is supported by the Division of Internal Medicine Immuno-Oncology Toxicity Award Program of the University of Texas MD Anderson Cancer Center. BS 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). AR is a consultant for Otsuka Pharmaceutical, and treasurer of the American Society of Onconephrology. SMH is supported by the Mayo Clinic K2R award. KB receives grant support from Olympia Morata Programme, Foundations Commission of University of Heidelberg, Rheumaliga Baden-Württemberg e.V., AbbVie, and Novartis. KB also serves as a consultant/receives speaker fee/travel reimbursements from AbbVie, BMS, Janssen, MSD, Viatris, Gilead/Galapagos, Lilly, Medac, Mundipharma, Novartis, Pﬁzer, Roche, and UCB. MES has served on a scientific advisory board for Mallinckrodt. LC serves as a consultant/receives honorarium/travel reimbursements from Pfizer, Bristol Myers Squibb, MSD. The remaining authors have no conflicts of interest or disclosures. MJS reports personal fees from NovoNordisk, Janssen, Mundipharma, AstraZeneca, Esteve, Fresenius, Ingelheim Lilly, Vifor, ICU, Pfizer, Bayer, Travere Therapeutics, GE Healthcare and Boehringer Ingelheim. MJS is a consultant for NovoNordisk, Travere Therapeutics, GE Healthcare, AstraZeneca, and Boehringer. MJS receives grant support form Boehringer Ingelheim, ISCIIII-FEDER and ISCIII-RETICS REDinREN, grant number PI17/00257, PI21/01292, RD16/0009/0030, RICORS RD21/0005/0016, Marató TV3 2020 421/C/2020, Marató TV3 2021 215/C/2021, and EIN2020-112338. MJS is elected Editor-in-Chief of Clinical Kidney Journal.

Figures

**Figure 1**
Flowchart. ATIN, acute tubulointerstitial nephritis; CS, corticosteroids; d, days; ICPi-AKI, immune checkpoint inhibitor-associated acute kidney injury; pred, prednisone.

**Figure 2**
Recurrent ICPi-AKI or death and longitudinal kidney function following completion of shorter versus longer duration of treatment with corticosteroids. (A) Kaplan-Meier curve showing risk of recurrent ICPi-AKI or death in the 30 days following completion of treatment with corticosteroids. N=56 in the shorter duration group; n=109 in the longer duration group. (B) Nadir serum creatinine in the shorter versus longer duration of corticosteroid therapy groups. Median serum creatinine levels are depicted, with error bars representing IQR. ICPi-AKI, immune checkpoint inhibitor-associated acute kidney injury.

See this image and copyright information in PMC

References

1. Cortazar FB, Marrone KA, Troxell ML, et al. . Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney Int 2016;90:638–47. 10.1016/j.kint.2016.04.008 - DOI - PMC - PubMed
1. Seethapathy H, Zhao S, Chute DF, et al. . The incidence, causes, and risk factors of acute kidney injury in patients receiving immune checkpoint inhibitors. Clin J Am Soc Nephrol 2019;14:1692–700. 10.2215/CJN.00990119 - DOI - PMC - PubMed
1. Gupta S, Short SAP, Sise ME, et al. . Acute kidney injury in patients treated with immune checkpoint inhibitors. J Immunother Cancer 2021;9:e003467. 10.1136/jitc-2021-003467 - DOI - PMC - PubMed
1. Saag KG, Koehnke R, Caldwell JR, et al. . Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 1994;96:115–23. 10.1016/0002-9343(94)90131-7 - DOI - PubMed
1. Del Castillo M, Romero FA, Argüello E, et al. . The spectrum of serious infections among patients receiving immune checkpoint blockade for the treatment of melanoma. Clin Infect Dis 2016;63:1490–3. 10.1093/cid/ciw539 - DOI - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI

Collaborators

Affiliations

Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources