Kidney Outcomes Associated with Immune Checkpoint Inhibitor Therapy in Patients with Cancer: A Global Cohort Analysis Using TriNetX

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with immune-related adverse events, including renal complications. The real-world burden of ICI-associated nephrotoxicity remains poorly defined. We aimed to assess the association between ICI exposure and the risk of acute kidney injury (AKI), end-stage renal disease (ESRD), nephrotic and nephritic syndromes, and mortality in a large international cohort. Methods: We used the TriNetX Global Collaborative Network (148 healthcare organizations) to identify adult patients (≥18 years) with a cancer diagnosis (ICD-10: C80.1) between 2005–2025. Cohort A (n=38,530) included patients treated with an FDA-approved ICI (atezolizumab, durvalumab, nivolumab, pembrolizumab, ipilimumab, avelumab, cemiplimab). Cohort B (n=526,284) included cancer patients without ICI exposure. Outcomes assessed included AKI (N17), ESRD (N18.6), nephrotic syndrome (N04), nephritic syndrome (N05), and all-cause mortality. Outcomes were compared using odds ratios, risk ratios, and Kaplan-Meier survival analysis. No propensity matching was performed. Results: Mortality was significantly higher in the ICI cohort (54.1% vs. 33.5%, OR 2.34; 95% CI: 2.29–2.39; p<0.001). AKI was more frequent in ICI-treated patients (25.9% vs. 17.3%, OR 1.68; 95% CI: 1.64–1.72; p<0.001). ESRD was slightly less common among ICI users (1.4% vs. 1.9%, OR 0.70; 95% CI: 0.64–0.77; p<0.001). Nephrotic syndrome occurred in 0.2% of both groups (OR 1.17; 95% CI: 0.94–1.46; p=0.17). Nephritic syndrome was more common in the ICI group (0.6% vs. 0.3%, OR 1.73; 95% CI: 1.50–1.99; p<0.001). Kaplan-Meier analysis confirmed significantly shorter survival and earlier onset of AKI and nephritic events in ICI-treated patients. Conclusion: In this large multicenter cohort, ICI therapy was associated with significantly increased risks of AKI, nephritic syndrome, and mortality. While ESRD was less common in the ICI group, the higher incidence of acute and immune-mediated renal syndromes warrants careful monitoring of kidney function in patients undergoing ICI therapy. Prospective studies are needed to clarify causality and identify modifiable risk factors.