Chronic kidney disease outcomes in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used in oncology, but long-term kidney outcomes in patients with pre-existing CKD (chronic kidney disease) are not well understood. We assessed CKD progression in patients with a baseline eGFR of 15-60 ml/min/1.73 m² who were treated with ICIs, comparing outcomes with those receiving chemotherapy. METHODS: We conducted a retrospective cohort study at Sheba Medical Center between 2015 and 2024. The primary outcome was a composite of new-onset end-stage kidney disease, initiation of kidney replacement therapy, or a >30% eGFR decline for at least 90 days. The secondary outcome was time to the first composite event. We used a Cox model with time-varying exposure and a propensity score-matched, new-user active comparator analysis to minimize selection bias. RESULTS: Of 3468 patients treated with ICIs, 885 had a baseline of eGFR 15-60 ml/min/1.73 m²; 208 met the inclusion criteria for CKD progression analysis. The composite outcome occurred in 22% of patients, with a shorter time-to-event in CKD stage 4 than in CKD stage 3 (27 vs. 83 months; P = 0.003). Factors associated with CKD progression included hydronephrosis (HR 5.6), smoking (HR 2.09), higher eosinophil counts (HR 4.8), and higher baseline creatinine (HR 3.0). Higher hemoglobin reduced the risk by 12%. ICI exposure was not associated with an increased risk compared with chemotherapy in the time-varying analysis (HR 0.83) or the matched active comparator (HR 0.81). These findings remained consistent in sensitivity analyses excluding patients with genitourinary malignancies. CONCLUSIONS: Among patients with eGFR 15-60 ml/min/1.73 m², systemic anticancer therapy carries a substantial risk of renal decline; however, ICIs do not increase the risk of CKD progression compared to chemotherapy. Outcomes are predominantly driven by baseline renal impairment and individual risk factors, highlighting the necessity of close renal monitoring rather than avoiding ICIs in this vulnerable population.