ABSTRACT
Objective:To investigate the incidence, risk factors, and outcomes of acute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs).Methods:A retrospective analysis was performed on the inpatients who received ICIs therapy in Beijing Shijitan Hospital, Capital Medical University from October 2015 to December 2020. According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI, patients were divided into AKI group and non-AKI group, and the patients in the AKI group were further divided into ICIs related AKI (ICIs-AKI) and AKI due to other etiologies. The clinical characteristics of the patients were compared. Multivariate logistic regression was used to analyze the influencing factors of AKI, and sensitivity analysis was used to evaluate the influencing factors of ICIs-AKI.Results:A total of 279 cancer patients over 18 years old were included in this study, in which 175(62.7%) were males. There were 41 patients (14.70%) in AKI group, including 25 patients (8.96%) in ICIs-AKI group and 16 patients (5.73%) in AKI due to other etiologies group. Patients in the AKI group were characterized by higher proportions of hypertension, diuretics use and baseline eGFR<60 ml·min -1·(1.73 m 2) -1, extrarenal immune-related adverse events (irAEs) and a lower plasma albumin level (all P<0.05). The patients in the ICIs-AKI group had higher proportions of new aseptic leukocyturia, blood eosinophil count>500/ml, combined extrarenal irAEs, glucocorticoid use and discontinued ICIs treatment (all P<0.05). Multivariate logistic regression results showed that hypertension ( OR=3.424, 95% CI 1.559-7.522, P=0.002), use of diuretics ( OR=4.620, 95% CI 2.111-10.112, P<0.001), baseline eGFR<60 ml·min -1·(1.73 m 2) -1 ( OR=3.668, 95% CI 1.336-10.070, P=0.012) and extrarenal irAEs ( OR=9.909, 95% CI 4.198-23.391, P<0.001) were associated with AKI in cancer patients receiving ICIs therapy. Sensitivity analysis indicated that the risk factors of ICIs-AKI included use of diuretics and baseline eGFR<60 ml·min -1·(1.73 m 2) -1, similar to the results of the above analysis, extrarenal irAEs ( OR=17.572, 95% CI 6.302-48.995, P<0.001) were also associated with ICIs-AKI independently. Conclusions:AKI is not uncommon in patients treated with ICIs. Concomitant hypertension, baseline eGFR<60 ml·min -1·(1.73 m 2) -1 and use of diuretics are independent risk factors for AKI in such patients. Patients should be alert to the risk of ICIs-AKI when appearing extrarenal irAEs. Distinguishing ICIs-AKI from AKI caused by other causes will present a frequent challenge to clinical practitioners.