Kidney function while on immune checkpoint inhibitors: Trends in incidence of acute kidney injury, and its causes and outcomes

Abstract

Background and objectives: Immune checkpoint inhibitor (ICI) use is increasing in the United States, real world data on acute kidney injury (AKI) in the expanding population are sparse. We evaluated trends in AKI incidence, and causes and management of AKI among 1914 persons receiving ICIs in a single center over a period of 5 years. Methods: We included all adults who received ICIs at the Stanford Healthcare System from July 1, 2015 to June 30, 2020. We defined AKI as an increase in serum creatinine to 1.5 times the baseline or an increase of ⩾0.3 mg/dL, and determined mean cumulative incidence of first and repeated episodes of AKI over three time periods. Results: Among the 1914 patients treated with ICIs, mean age was 64.9 (SD 14.3) years, 43% were women, 25% had baseline chronic kidney disease (CKD), 34% had lung and 23% had skin cancer as the indication. The overall cumulative incidence of any AKI and immune-related AKI at 1 year after initiating immunotherapy was 32% and 1.3% respectively. Among 586 cases of AKI, the most common cause was volume depletion (64%). Although 4% of AKI was immune-related, ICI therapy was discontinued in 14% of patients with AKI. Nephrology was consulted in 6%. The risk for AKI was higher among patients with a comorbidity index ⩾3 (vs CMI 0, HR 1.65 [95% CI 1.26–2.17]), digestive system cancer (vs skin cancer, 1.65 [1.13–2.43]), and lower baseline estimated glomerular filtration rate (30–59 and <30 vs >60) (HR 1.69 [1.32–2.16] and 1.85 [1.16–2.97] respectively). Conclusions: AKI occurs in up to 1 in 3 patients, and 1 in 10 will have repeated episodes during the first year of ICI therapy. Incidence of AKI has remained similar over 5-year time span. The cause of AKI while on ICI is rarely an immune-related adverse event.