Acute kidney injury in programmed cell death protein-1/programmed death-ligand 1 inhibitor-treated locally advanced/metastatic renal cell carcinoma: The risk factors and the influence on the clinical outcome

A BSTRACT Objectives: Programmed cell death protein-1/programmed death-ligand 1 inhibitors (PD-1/PD-L1i) improve survival in advanced renal cell carcinoma (RCC) but may increase the risk of acute kidney injury (AKI). This study evaluated the incidence of AKI, associated risk factors, and clinical outcomes among PD-1/PD-L1i users. Materials and Methods: Using the TriNetX Global Collaborative Network, we identified adults with Stage 3–4 RCC diagnosed between 2010 and 2025. Patients receiving PD-1/PD-L1i within 1 year of RCC diagnosis were compared with non-users. Exclusion criteria included age <18 years, bladder or transitional cell carcinoma, baseline estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m 2 , and death within 1 year of diagnosis. Propensity score matching (1:1) was performed using demographics and comorbidities. Outcomes included AKI incidence and overall survival (OS) over 3 years, and mortality, major adverse cardiovascular events (MACE), and sepsis over 2 years among PD-1/PD-L1i users with versus without AKI. A sensitivity analysis limited to patients with eGFR >30 mL/min/1.73 m 2 assessed robustness. Results: Among 724 PD-1/PD-L1i users and 6643 nonusers, 712 matched pairs were analyzed. PD-1/PD-L1i therapy was associated with a higher incidence of AKI compared with matched non-users, and this association remained significant in sensitivity analyses. Among PD-1/PD-L1i users, AKI did not significantly affect OS or MACE but increased in sepsis. Subgroup analyses identified diabetes mellitus, aminoglycoside exposure, and prior nephrectomy as independent predictors of AKI, whereas preserved renal function (eGFR >60 mL/min/1.73 m 2 ) was protective. Conclusion: PD-1/PD-L1i therapy increases AKI risk in advanced RCC but does not compromise short-term survival or major clinical outcomes. Recognizing high-risk subgroups may guide closer renal monitoring during immunotherapy.