У пациентов с генитоурологическими раком и тяжелой хронической болезнью почек иммунотерапия снижает выживаемость и повышает риск почечной недостаточности

Among patients with genitourinary cancers treated with immune checkpoint inhibitors (ICIs), the presence of advanced chronic kidney disease (CKD) is associated with worse survival and greater renal injury, investigators report. “ICIs reactivate exhausted antitumor T cells in the tumor microenvironment, but uremia has been shown to impair CD4⁺ T-cell activation and proliferation, raising concerns that [advanced] CKD may attenuate antitumor immune responses,” Yin-Shen Chen, MD, of Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan, and colleagues wrote in Cancer Immunology and Immunotherapy. Other factors also may contribute to worse treatment tolerance and survival. Advanced CKD is associated with lower physiologic reserve, cardiovascular and metabolic comorbidities, chronic inflammation, malnutrition, and susceptibility to complications. Using data from 63 centers in the 2015-2023 TriNetX US Collaborative Network database, the investigators propensity-score matched 2196 patients with advanced CKD and 2196 patients with early CKD who were taking ICIs for renal cell carcinoma (RCC) or urothelial carcinoma. Advanced CKD included patients with stage 4 or 5 CKD, including end-stage kidney disease (ESKD) and those undergoing maintenance dialysis. Early CKD was defined as stage 1 to 2. An estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73m2 was the threshold separating the 2 groups. Kidney transplant recipients were excluded. The primary outcome was all-cause mortality at 2 years. The secondary outcome was immune-related adverse events. Over 2 years, 44.7% of treated patients with advanced CKD died compared with 35.5% of treated patients with early CKD. The risk for all-cause death was nearly 1.4-fold higher for patients with advanced CKD (hazard ratio [HR], 1.372; 95% CI, 1.248-1.507). The risk for immune-related adverse events also was elevated in advanced vs early CKD (HR, 1.141; 95% CI, 1.058-1.231), particularly acute kidney injury (AKI; HR, 1.662; 95% CI, 1.500-1.840). The risks of AKI and death increased after 3 months of ICI use and remained increased through 60 months. These trends were consistent by cancer type, dialysis status, and younger vs older age. “These findings suggest that CKD alone should not automatically preclude ICI use in carefully selected patients, but patients with [advanced] CKD require close renal monitoring and multidisciplinary management throughout treatment,” Dr Chen’s team concluded. References: Chen YS, Yu CC, Chang R, Wu SH, Sun CK, Huang SH. Efficacy of checkpoint inhibitors in genitourinary cancers with advanced chronic kidney disease. Cancer Immunol Immunother. doi:10.1007/s00262-026-04482-0