Guo Nan, Gao Ping, Jin Haobin, Sheng Jia, Shi Yaru, Bi Yunyan, Lyu Zhimei, Zhang Wen
To explore the characteristics and factors affecting the occurrence of renal injury in patients with abnormal biochemical indexes of renal function after the use of immune checkpoint inhibitors (ICIs), and to provide reference for selection of clinical treatment regimen. Methods Patients who were treated with immune checkpoint inhibitors researched and developed independently in China including camrelizumab, sintilimab, tislelizumab， and toripalimab from March 1, 2021 to February 28, 2022 and showed estimated glomerular filtration rate (eGFR) <90-ml/(min·1.73 m2) and/or serum creatinine (Scr)>105-μmol/L were retrieved from the China Hospital Pharmacovigilance System. The clinical data including general information, anti-tumor treatment regimen, laboratory test results, and concomitant medications were collected. Patients were divided into kidney injury group and non-kidney injury group, and all the clinical characteristics were compared between the 2 groups, the influencing factors of kidney injury were analyzed using a binary logistic regression model, the odds ratio (OR) and its 95% confidence interval (CI) were calculated. Results A total of 222 patients were entered in the analysis, including 170 males and 52 females, with a median age of 67 (36, 85) years. Of them, 144 patients were treated with carrilizumab, 38 with sindilizumab, 31 with tirelizumab, and 9 with treprolizumab; 29 patients (13.1%) developed kidney injury, including 26 cases of grade 1 and 3 cases of grade 2 renal injuries; the time of renal injury occurrence was 19-355 days after the first application of ICIs, and the median time was 108 days. After diagnosed of kidney injury, 13 out of 29 patients stopped ICIs, of which 6 had recovered kidney function and 7 had no improvement; 16 patients continued the ICIs treatment, of which 10 patients had recovered or improved kidney function and 6 had no improvement. The clinical characteristics of patients in the 2 groups were compared, and 10 variables including age, gender, baseline renal function, previous use of carboplatin, previous radiotherapy, combined chemotherapy containing cisplatin, combined paclitaxel chemotherapy, combined tyrosine kinase inhibitor (TKI) anti-vascular therapy, combined proton pump inhibitors, and combined radiotherapy were screened for the binary logistic regression analysis. The results showed that female (OR=3.046, 95%CI: 1.149-8.077), ≤65 years (OR=3.649, 95%CI: 1.435-9.274), combined TKI anti-vascular therapy (OR=4.773, 95%CI: 1.496-15.227), and combined radiotherapy (OR=8.655, 95%CI: 1.268-59.076) were independent risk factors for the development of kidney injury. Conclusions The incidence of kidney injury in patients with eGFR <90-ml/(min·1.73 m2) and/or Scr >105-μmol/L after using ICIs is 13.1%. In these patients, female, ≤65 years, combined TKI anti-vascular therapy, and combined radiotherapy may be risk factors for the development of ICI-associated kidney injury.
