CKD Outcomes in Patients Treated with Immune Checkpoint Inhibitors

Background: Immune checkpoint inhibitors (ICIs) are a key cancer therapy targeting regulators such as PD-1, PD-L1, CTLA-4, and LAG-3 to enhance T-cell immunity. However, ICIs can lead to immune-related adverse events (irAEs) in up to 95% of patients, with renal irAEs, including ICI-associated acute kidney injury (AKI), being rare but well-documented. However, data on long-term renal outcomes in chronic kidney disease (CKD) patients, particularly those with comorbidities, remain limited. Methods: A retrospective cohort study of 209 adult patients with baseline eGFR 15-60 mL/min/ who received ICIs and survived ≥12 months. CKD outcomes were assessed using a composite endpoint of new-onset end-stage kidney disease (ESKD), initiation of kidney replacement therapy, and sustained ≥30% decline in eGFR from baseline for > 90 days. Results: A total of 101 patients (48%) met the composite renal endpoint, with 50% reaching the outcome within 24 months of ICI therapy initiation. There were no significant differences between groups reaching or not reaching the composite endpoint in clinical factors including age, sex, baseline serum creatinine, eGFR, cancer type, or ICI regimen (PD-1, PD-L1, CTLA-4, or combination). Patients meeting the composite endpoint had higher rates of diabetes mellitus ( DM, 22% vs. 36%, P = 0.047), cardiovascular events (CVD, 5.6% vs. 13.9%, P = 0.07), and smoking history (20% vs. 41%, P = 0.002). They were also more likely to be taking proton pump inhibitors (PPI, P= 0.09), diuretics (P = 0.018), angiotensin-converting enzyme inhibitors (ACE-I, P = 0.02), and nephrotoxic chemotherapies (P = 0.087). Multivariable analysis identified DM, CVD, smoking, and ACE-I use as independent predictors for the composite renal outcome. Mortality was significantly higher in patients meeting the renal composite endpoint (69% vs. 39%, P. value < 0.001). Conclusion: Nearly half of CKD patients treated with ICIs experience significant renal deterioration within 24 months, driven by comorbid risk factors such as DM, CVD and smoking. These findings highlight the need for closer renal monitoring and preemptive risk mitigation strategies in this vulnerable population. Further prospective studies are warranted to elucidate the mechanisms underlying these renal outcomes and optimize care for CKD patients undergoing ICI therapies.