Acute Kidney Injury in Patients receiving Immune Checkpoint Inhibitors: a Retrospective Real-world Study

Nuttha Lumlertgul; Pietro Vassallo; Florence Tydeman; Natasha Lewis; Abigail Hobill; Kittisak Weerapolchai; Nurul Zaynah Nordin; Nina Seylanova; Luke Martin; Armando Cennamo; Yanzhong Wang; Anne Rigg; Nisha Shaunak; Marlies Ostermann

doi:10.1016/j.ejca.2023.112967

Acute Kidney Injury in Patients receiving Immune Checkpoint Inhibitors: a Retrospective Real-world Study

Nuttha Lumlertgul, Pietro Vassallo, Florence Tydeman, Natasha Lewis, Abigail Hobill, Kittisak Weerapolchai, Nurul Zaynah Nordin, Nina Seylanova, Luke Martin, Armando Cennamo, Yanzhong Wang, Anne Rigg, Nisha Shaunak, Marlies Ostermann

Population Health Sciences

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

3 Citations (Scopus)

Abstract

Background: Immune checkpoint inhibitors (ICPi) can cause immune-related adverse events (irAEs) including acute kidney injury (AKI). We investigated the incidence of ICPi-associated AKI (ICPi-AKI) and AKI from other causes (non-ICPi-AKI) in cancer patients treated with ICPi. Methods: This was a single-centre retrospective cohort study of patients receiving ICPi therapy between December 2011 and August 2020. AKI was defined and staged by the Kidney Disease Improving Global Outcomes creatinine criteria. The primary outcome was the incidence of AKI and ICPi-AKI. Results: A total of 1037 patients were included in the final analysis. The median age was 63 years, 60% were male, and 22% had pre-existing chronic kidney disease. Overall, 189 patients (18.2%) developed AKI of whom 37 patients (3.6%) had ICPi-AKI. In patients with progressive cancer, AKI was not associated with increased mortality. In treatment responders, non-ICPi-AKI was associated with an increased risk of mortality (adjusted hazard ratio [HR] 2.03; 95% confidence interval [CI] 1.12–3.67), whereas ICPi-AKI was not linked to an increased risk of death (adjusted HR 0.60; 95% CI 0.18–1.96). Patients with ICPi-AKI were more likely to have higher AKI stages and less likely to have complete kidney recovery compared with non-ICPi-AKI (54% versus 79%, p = 0.01). Conclusion: AKI was common in cancer patients treated with ICPi. Patients with ICPi-AKI had worse kidney outcomes compared to those with AKI from other causes. However, non-ICPi-AKI was associated with a higher risk of death. These findings emphasise the importance of identifying different sub-phenotypes of AKI.

Original language	English
Article number	112967
Journal	European Journal of Cancer
Volume	191
DOIs	https://doi.org/10.1016/j.ejca.2023.112967
Publication status	Published - Sept 2023

Keywords

immune checkpoint inhibitors
immunotherapy
acute kidney injury
cancer
chronic kidney disease
malignancy

UN SDGs

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

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10.1016/j.ejca.2023.112967

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Lumlertgul, N., Vassallo, P., Tydeman, F., Lewis, N., Hobill, A., Weerapolchai, K., Nordin, N. Z., Seylanova, N., Martin, L., Cennamo, A., Wang, Y., Rigg, A., Shaunak, N., & Ostermann, M. (2023). Acute Kidney Injury in Patients receiving Immune Checkpoint Inhibitors: a Retrospective Real-world Study. European Journal of Cancer, 191, Article 112967. https://doi.org/10.1016/j.ejca.2023.112967

@article{8100e640f1c24a43afefcf9ce04c46ba,

title = "Acute Kidney Injury in Patients receiving Immune Checkpoint Inhibitors: a Retrospective Real-world Study",

abstract = "Background: Immune checkpoint inhibitors (ICPi) can cause immune-related adverse events (irAEs) including acute kidney injury (AKI). We investigated the incidence of ICPi-associated AKI (ICPi-AKI) and AKI from other causes (non-ICPi-AKI) in cancer patients treated with ICPi. Methods: This was a single-centre retrospective cohort study of patients receiving ICPi therapy between December 2011 and August 2020. AKI was defined and staged by the Kidney Disease Improving Global Outcomes creatinine criteria. The primary outcome was the incidence of AKI and ICPi-AKI. Results: A total of 1037 patients were included in the final analysis. The median age was 63 years, 60% were male, and 22% had pre-existing chronic kidney disease. Overall, 189 patients (18.2%) developed AKI of whom 37 patients (3.6%) had ICPi-AKI. In patients with progressive cancer, AKI was not associated with increased mortality. In treatment responders, non-ICPi-AKI was associated with an increased risk of mortality (adjusted hazard ratio [HR] 2.03; 95% confidence interval [CI] 1.12–3.67), whereas ICPi-AKI was not linked to an increased risk of death (adjusted HR 0.60; 95% CI 0.18–1.96). Patients with ICPi-AKI were more likely to have higher AKI stages and less likely to have complete kidney recovery compared with non-ICPi-AKI (54% versus 79%, p = 0.01). Conclusion: AKI was common in cancer patients treated with ICPi. Patients with ICPi-AKI had worse kidney outcomes compared to those with AKI from other causes. However, non-ICPi-AKI was associated with a higher risk of death. These findings emphasise the importance of identifying different sub-phenotypes of AKI.",

keywords = "immune checkpoint inhibitors, immunotherapy, acute kidney injury, cancer, chronic kidney disease, malignancy",

author = "Nuttha Lumlertgul and Pietro Vassallo and Florence Tydeman and Natasha Lewis and Abigail Hobill and Kittisak Weerapolchai and Nordin, {Nurul Zaynah} and Nina Seylanova and Luke Martin and Armando Cennamo and Yanzhong Wang and Anne Rigg and Nisha Shaunak and Marlies Ostermann",

note = "Funding Information: Nurul Z. Nordin did this work during her Acute Kidney Injury (AKI) fellowship at Guy{\textquoteright}s & St Thomas{\textquoteright} NHS Foundation Trust under the International Society of Nephrology (ISN) fellowship grant. Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",

year = "2023",

month = sep,

doi = "10.1016/j.ejca.2023.112967",

language = "English",

volume = "191",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

Lumlertgul, N, Vassallo, P, Tydeman, F, Lewis, N, Hobill, A, Weerapolchai, K, Nordin, NZ, Seylanova, N, Martin, L, Cennamo, A, Wang, Y, Rigg, A, Shaunak, N & Ostermann, M 2023, 'Acute Kidney Injury in Patients receiving Immune Checkpoint Inhibitors: a Retrospective Real-world Study', European Journal of Cancer, vol. 191, 112967. https://doi.org/10.1016/j.ejca.2023.112967

TY - JOUR

T1 - Acute Kidney Injury in Patients receiving Immune Checkpoint Inhibitors

T2 - a Retrospective Real-world Study

AU - Lumlertgul, Nuttha

AU - Vassallo, Pietro

AU - Tydeman, Florence

AU - Lewis, Natasha

AU - Hobill, Abigail

AU - Weerapolchai, Kittisak

AU - Nordin, Nurul Zaynah

AU - Seylanova, Nina

AU - Martin, Luke

AU - Cennamo, Armando

AU - Wang, Yanzhong

AU - Rigg, Anne

AU - Shaunak, Nisha

AU - Ostermann, Marlies

N1 - Funding Information: Nurul Z. Nordin did this work during her Acute Kidney Injury (AKI) fellowship at Guy’s & St Thomas’ NHS Foundation Trust under the International Society of Nephrology (ISN) fellowship grant. Publisher Copyright: © 2023 Elsevier Ltd

PY - 2023/9

Y1 - 2023/9

N2 - Background: Immune checkpoint inhibitors (ICPi) can cause immune-related adverse events (irAEs) including acute kidney injury (AKI). We investigated the incidence of ICPi-associated AKI (ICPi-AKI) and AKI from other causes (non-ICPi-AKI) in cancer patients treated with ICPi. Methods: This was a single-centre retrospective cohort study of patients receiving ICPi therapy between December 2011 and August 2020. AKI was defined and staged by the Kidney Disease Improving Global Outcomes creatinine criteria. The primary outcome was the incidence of AKI and ICPi-AKI. Results: A total of 1037 patients were included in the final analysis. The median age was 63 years, 60% were male, and 22% had pre-existing chronic kidney disease. Overall, 189 patients (18.2%) developed AKI of whom 37 patients (3.6%) had ICPi-AKI. In patients with progressive cancer, AKI was not associated with increased mortality. In treatment responders, non-ICPi-AKI was associated with an increased risk of mortality (adjusted hazard ratio [HR] 2.03; 95% confidence interval [CI] 1.12–3.67), whereas ICPi-AKI was not linked to an increased risk of death (adjusted HR 0.60; 95% CI 0.18–1.96). Patients with ICPi-AKI were more likely to have higher AKI stages and less likely to have complete kidney recovery compared with non-ICPi-AKI (54% versus 79%, p = 0.01). Conclusion: AKI was common in cancer patients treated with ICPi. Patients with ICPi-AKI had worse kidney outcomes compared to those with AKI from other causes. However, non-ICPi-AKI was associated with a higher risk of death. These findings emphasise the importance of identifying different sub-phenotypes of AKI.

AB - Background: Immune checkpoint inhibitors (ICPi) can cause immune-related adverse events (irAEs) including acute kidney injury (AKI). We investigated the incidence of ICPi-associated AKI (ICPi-AKI) and AKI from other causes (non-ICPi-AKI) in cancer patients treated with ICPi. Methods: This was a single-centre retrospective cohort study of patients receiving ICPi therapy between December 2011 and August 2020. AKI was defined and staged by the Kidney Disease Improving Global Outcomes creatinine criteria. The primary outcome was the incidence of AKI and ICPi-AKI. Results: A total of 1037 patients were included in the final analysis. The median age was 63 years, 60% were male, and 22% had pre-existing chronic kidney disease. Overall, 189 patients (18.2%) developed AKI of whom 37 patients (3.6%) had ICPi-AKI. In patients with progressive cancer, AKI was not associated with increased mortality. In treatment responders, non-ICPi-AKI was associated with an increased risk of mortality (adjusted hazard ratio [HR] 2.03; 95% confidence interval [CI] 1.12–3.67), whereas ICPi-AKI was not linked to an increased risk of death (adjusted HR 0.60; 95% CI 0.18–1.96). Patients with ICPi-AKI were more likely to have higher AKI stages and less likely to have complete kidney recovery compared with non-ICPi-AKI (54% versus 79%, p = 0.01). Conclusion: AKI was common in cancer patients treated with ICPi. Patients with ICPi-AKI had worse kidney outcomes compared to those with AKI from other causes. However, non-ICPi-AKI was associated with a higher risk of death. These findings emphasise the importance of identifying different sub-phenotypes of AKI.

KW - immune checkpoint inhibitors

KW - immunotherapy

KW - acute kidney injury

KW - cancer

KW - chronic kidney disease

KW - malignancy

UR - http://www.scopus.com/inward/record.url?scp=85165676961&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2023.112967

DO - 10.1016/j.ejca.2023.112967

M3 - Article

SN - 0959-8049

VL - 191

JO - European Journal of Cancer

JF - European Journal of Cancer

M1 - 112967

ER -

Acute Kidney Injury in Patients receiving Immune Checkpoint Inhibitors: a Retrospective Real-world Study

Abstract

Keywords

UN SDGs

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