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.

Background and Aims Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of autoimmune-related 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. Method Patients receiving checkpoint inhibitors between January 2013 and May 2020 were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in creatinine of ≥1.5 times the baseline value. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent kidney injury was diagnosed in AKI patients with a final creatinine measurement of >1.3 times the baseline value. Results Out of 676 patients receiving checkpoint inhibitors, AKI occurred in 96 (14.2%) patients. Chart review showed that AKI was checkpoint inhibitor-associated in 32 (4.7%) patients. Baseline variables associated with AKI were a primary gynecological malignancy (HR 3.91, 95% CI 1.55 to 9.85), treatment with checkpoint inhibitor ipilimumab (HR 2.31, 95% CI 1.03 to 5.20), and pre-existent use of a diuretic (HR 2.61, 95% CI 1.21 to 5.60), an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker (HR 2.49, 95% CI 1.10 to 5.60), and a proton pump inhibitor (HR 1.69, 95% CI 1.04 to 2.75). In 35.4% of the patients who had developed AKI, persistent kidney dysfunction was observed at the end of follow-up. Patients who developed AKI had a 2.13-fold (95% CI 1.58 to 2.87) increased mortality risk compared to patients who did not develop AKI. Mortality risk was not increased by checkpoint inhibitor-associated AKI (HR 1.11, 95% CI 0.64 to 1.92), but only by AKI related to other causes (HR 2.87, 95% CI 2.04 to 4.04). Conclusion Patients receiving checkpoint inhibitors frequently develop AKI, however, checkpoint inhibitor-associated AKI does not seem to increase mortality.