Maen Abdelrahim1, Omar Mamlouk2, Heather Lin3, Jamie Lin2, Valda Page2, Noha Abdel-Wahab4,5,6, Joshua Swan7, Umut Selamet8, Cassian Yee6, Adi Diab6, Wadi Suki9, Ala Abudayyeh2. 1. Institute of Academic Medicine and Weill Cornell Medical College, Houston Methodist Cancer Center, Houston, Texas, USA. 2. Section of Nephrology, Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 3. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 4. Rheumatology and Rehabilitation Department, Assiut University Hospitals, Faculty of Medicine, Assiut, Egypt. 5. Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 6. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 7. Department of System Pharmacy, Houston Methodist, Houston, Texas, USA. 8. Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. 9. Department of Medicine, Nephrology, Houston Methodist Hospital, Houston, Texas, USA.
Abstract
Background: The incidence of renal immune-related adverse events (irAEs) is reported to be 3.8%, with varied definitions of acute kidney injury (AKI). This study reports a 10-year experience at MD Anderson Cancer Center of patients diagnosed with melanoma and treated with immune checkpoint inhibitors (ICIs) and evaluated the incidence of AKI, associated factors, and its association with overall survival. Methods: A retrospective chart review (2010-2019) of all patients with melanoma treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab was performed. All available serum creatinine data were extracted and used to calculate the estimated GFR (eGFR) using the CKD Epi equation, and to diagnose AKI using the two KDIGO (Kidney Disease: Improving Global Outcomes) criteria for defining stage I AKI in 1664 unique patients. Cumulative incidence rates of AKI after initiation of ICIs were calculated in the presence of death as a competing risk. The effects of covariates on the cumulative incidence function of AKI were evaluated in a univariant and multivariable analysis. Overall survival was estimated by Kaplan-Meier method in accordance to the occurrence of AKI. Results: The incidence of AKI by definitions 1a and 1b were 3.49% and 3.33%, respectively. After adjudication, AKI attributable to ICI was 58% and 65% of the overall incidence of AKI in each definition respectively. Increasing age was associated with decreased risk of AKI. Asian race was associated with a higher risk of AKI. Comorbidities were not associated with increased risk of AKI while use of proton pump inhibitors (PPI), ipilimumab or ICI combinations were significantly associated with AKI. AKI was not significantly associated with overall survival. Immune-related adverse events (irAEs) occurred in 30% of patients with AKI but their incidence was not different in patients with AKI attributable to ICI versus other AKI. Conclusions: In a large population of patients with melanoma treated with ICIs, an accurate documentation of AKI in setting of ICI use and predictors associated is presented. AKI following ICI use is infrequent, not associated with mortality, and associated with the use of ipilimumab, ICI combinations and PPIs.
Background: The incidence of renal immune-related adverse events (irAEs) is reported to be 3.8%, with varied definitions of acute kidney injury (AKI). This study reports a 10-year experience at MD Anderson Cancer Center of patients diagnosed with melanoma and treated with immune checkpoint inhibitors (ICIs) and evaluated the incidence of AKI, associated factors, and its association with overall survival. Methods: A retrospective chart review (2010-2019) of all patients with melanoma treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab was performed. All available serum creatinine data were extracted and used to calculate the estimated GFR (eGFR) using the CKD Epi equation, and to diagnose AKI using the two KDIGO (Kidney Disease: Improving Global Outcomes) criteria for defining stage I AKI in 1664 unique patients. Cumulative incidence rates of AKI after initiation of ICIs were calculated in the presence of death as a competing risk. The effects of covariates on the cumulative incidence function of AKI were evaluated in a univariant and multivariable analysis. Overall survival was estimated by Kaplan-Meier method in accordance to the occurrence of AKI. Results: The incidence of AKI by definitions 1a and 1b were 3.49% and 3.33%, respectively. After adjudication, AKI attributable to ICI was 58% and 65% of the overall incidence of AKI in each definition respectively. Increasing age was associated with decreased risk of AKI. Asian race was associated with a higher risk of AKI. Comorbidities were not associated with increased risk of AKI while use of proton pump inhibitors (PPI), ipilimumab or ICI combinations were significantly associated with AKI. AKI was not significantly associated with overall survival. Immune-related adverse events (irAEs) occurred in 30% of patients with AKI but their incidence was not different in patients with AKI attributable to ICI versus other AKI. Conclusions: In a large population of patients with melanoma treated with ICIs, an accurate documentation of AKI in setting of ICI use and predictors associated is presented. AKI following ICI use is infrequent, not associated with mortality, and associated with the use of ipilimumab, ICI combinations and PPIs.
Authors: Peter Attia; Giao Q Phan; Ajay V Maker; Michael R Robinson; Martha M Quezado; James C Yang; Richard M Sherry; Suzanne L Topalian; Udai S Kammula; Richard E Royal; Nicholas P Restifo; Leah R Haworth; Catherine Levy; Sharon A Mavroukakis; Geoff Nichol; Michael J Yellin; Steven A Rosenberg Journal: J Clin Oncol Date: 2005-08-08 Impact factor: 44.544
Authors: Frank B Cortazar; Kristen A Marrone; Megan L Troxell; Kenneth M Ralto; Melanie P Hoenig; Julie R Brahmer; Dung T Le; Evan J Lipson; Ilya G Glezerman; Jedd Wolchok; Lynn D Cornell; Paul Feldman; Michael B Stokes; Sarah A Zapata; F Stephen Hodi; Patrick A Ott; Michifumi Yamashita; David E Leaf Journal: Kidney Int Date: 2016-06-07 Impact factor: 10.612
Authors: Harish Seethapathy; Sophia Zhao; Donald F Chute; Leyre Zubiri; Yaa Oppong; Ian Strohbehn; Frank B Cortazar; David E Leaf; Meghan J Mooradian; Alexandra-Chloé Villani; Ryan J Sullivan; Kerry Reynolds; Meghan E Sise Journal: Clin J Am Soc Nephrol Date: 2019-10-31 Impact factor: 8.237
Authors: Marlies Ostermann; Rinaldo Bellomo; Emmanuel A Burdmann; Kent Doi; Zoltan H Endre; Stuart L Goldstein; Sandra L Kane-Gill; Kathleen D Liu; John R Prowle; Andrew D Shaw; Nattachai Srisawat; Michael Cheung; Michel Jadoul; Wolfgang C Winkelmayer; John A Kellum Journal: Kidney Int Date: 2020-04-26 Impact factor: 10.612
Authors: 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 DeMauro Renaghan; David I Ortiz-Melo; Sunil Rangarajan; A Bilal Malik; Jonathan J Hogan; Alex R Dinh; Daniel 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 Journal: J Am Soc Nephrol Date: 2020-01-02 Impact factor: 10.121
Authors: Krista Dubin; Margaret K Callahan; Boyu Ren; Raya Khanin; Agnes Viale; Lilan Ling; Daniel No; Asia Gobourne; Eric Littmann; Curtis Huttenhower; Eric G Pamer; Jedd D Wolchok Journal: Nat Commun Date: 2016-02-02 Impact factor: 14.919
Authors: Houssein Safa; Daniel H Johnson; Van Anh Trinh; Theresa E Rodgers; Heather Lin; Maria E Suarez-Almazor; Faisal Fa'ak; Chantal Saberian; Cassian Yee; Michael A Davies; Sudhakar Tummala; Karin Woodman; Noha Abdel-Wahab; Adi Diab Journal: J Immunother Cancer Date: 2019-11-21 Impact factor: 13.751