Related Experiment Video
Updated: Nov 2, 2025
Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice
Published on: February 2, 2024
Immune checkpoint inhibitor-associated acute kidney injury and mortality: An observational study
Marije S Koks1, Gurbey Ocak1,2,3, Britt B M Suelmann4
1Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Background:
Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors.
Methods:
Patients receiving checkpoint inhibitors between January 2013 and May 2020 at the University Medical Center Utrecht, the Netherlands, were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in serum creatinine of ≥1.5 times the baseline value, based on the Kidney Disease: Improving Global Outcomes criteria. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent renal dysfunction was diagnosed in AKI patients with a final serum creatinine measurement of >1.3 times the baseline value.
Results:
Among 676 patients receiving checkpoint inhibitors, the overall incidence of AKI was 14.2%. Baseline variables independently associated with AKI were a gynecologic malignancy, monotherapy with ipilimumab, and the use of a diuretic, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or proton pump inhibitor at baseline. AKI was checkpoint inhibitor-associated in one third of all patients with AKI. Checkpoint inhibitor-associated AKI was mostly low-grade, occurred a median of 15 weeks after checkpoint inhibitor initiation, and resulted in persistent renal dysfunction in approximately 40% of the patients. Patients with all-cause AKI had a twofold increased mortality risk, but checkpoint inhibitor-associated AKI was not associated with increased mortality.
Conclusions:
In this study, patients receiving checkpoint inhibitors frequently developed AKI due to various etiologies. AKI directly related to the effect of checkpoint inhibitor toxicity did not increase mortality. However, AKI not related to the effect of checkpoint inhibitor toxicity was associated with increased mortality.
Insights
Immune checkpoint inhibitors can cause acute kidney injury (AKI) in 14.2% of patients. While AKI from other causes increased mortality, AKI directly from checkpoint inhibitor toxicity did not significantly raise death risk.
Area of Science:
- Nephrology
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) are crucial cancer therapies.
- These treatments can induce a range of adverse effects, notably acute kidney injury (AKI).
- Understanding AKI in ICI recipients is vital for patient management.
Purpose of the Study:
- To determine the incidence of AKI in patients treated with ICIs.
- To identify risk factors associated with ICI-induced AKI.
- To evaluate renal outcomes and mortality in patients experiencing AKI.
Main Methods:
- Retrospective cohort study of 676 patients receiving ICIs (Jan 2013-May 2020).
- AKI defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria (serum creatinine increase ≥1.5x baseline).
- Cox regression analysis used to identify risk factors and assess mortality impact.
Main Results:
- Overall AKI incidence was 14.2%.
- Independent risk factors included gynecologic malignancy, ipilimumab monotherapy, and concurrent use of diuretics, ACE inhibitors/ARBs, or PPIs.
- Approximately 40% of patients with ICI-associated AKI experienced persistent renal dysfunction; however, this specific type of AKI did not increase mortality.
Conclusions:
- Patients on ICIs frequently develop AKI from diverse causes.
- AKI directly linked to ICI toxicity did not elevate mortality risk.
- AKI from other etiologies in ICI patients was associated with increased mortality.
Related Concept Videos
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:22Acute Kidney Injury I: Introduction
01:29Acute Kidney Injury II: Pathophysiology
01:29Acute Kidney Injury III: Clinical Manifestations
01:20Acute Kidney Injury V: Interprofessional Care
01:22Acute Kidney Injury VI: Nursing Management