Factors associated with acute kidney injury among patients with cancer treated with immune checkpoint inhibitor therapy: A population-based study.

2584 Background: Cancer immune checkpoint inhibitor (ICI) therapy may be associated with kidney immune-related adverse events (IRAEs) and other causes of acute kidney injury (AKI). In clinical trials, the frequency of AKI events was uncommon, however, further real-world study is warranted. Methods: We evaluated the proportion of AKI events among patients with advanced cancer (bladder, head and neck, lung, kidney and malignant melanoma) treated with ICI therapy in Ontario, Canada from 2012 - 2018. AKI was defined by a rise in the concentration of serum creatinine as per Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A multivariable regression model was used to identify predictors of AKI while accounting for the competing risk of death. Results: A total of 4,380 patients received ICI therapy. In follow-up, 1,283 (29%) had recorded AKI event (any stage AKI) and 289 (7%) had a severe AKI event (≥ stage 2). Median time to AKI was 6 months (Interquartile Range 2-16 months) and ≤ 1 % of patients received dialysis therapy. Within 30 days of any observed AKI event, 853 (58%) discontinued ICI therapy, 372 (29%) were hospitalized and 266 (21%) died. Mortality was significantly higher among patients who experiencing a severe AKI event (≥ stage 2) as compared to patients with a less severe AKI event (stage 1) or no observed AKI event. Among patients alive at 30 days following an AKI event, 14% received an outpatient corticosteroid or immunosuppressive therapy prescription, 7% had a visit with a nephrologist. Characteristics associated with a higher risk of AKI included female sex, bladder or kidney cancer (reference malignant melanoma), history of hypertension or diabetes, higher Charlson comorbidity score, a baseline estimated glomerular filtration rate less than 30 mL/min/1.73 m2, or outpatient prescription for either a proton pump inhibitor or non-steroidal anti-inflammatory drug. Among patients with an AKI event and treatment discontinuation, re-challenge of ICI therapy was infrequent (16%) with a significant risk of a recurrent AKI event (57%). Conclusions: In a population-based study among patients with cancer receiving ICI therapy, the rate of AKI was common (29%) but severe AKI was less frequent (7%). Rates of ICI discontinuation, hospitalization and death are substantial following an AKI event. Kidney function should be monitored carefully among patients undergoing ICI therapy who have common risk factors for developing renal disease. Nephrology consultation may be optimized among patients who develop a severe AKI event, especially among individuals who are considered for ICI therapy re-challenge.