Immune-Related, Kidney, and Clinical Outcomes in Patients with Renal Cell Carcinoma with Autoimmune Disease Treated with Immune Checkpoint Inhibitors: A Propensity-Score Matched Analysis

Background: Safety of immune checkpoint inhibitors (ICIs) in patients with pre-existing autoimmune disease (AID) and renal cell carcinoma (RCC) remains unclear. Current guidelines recommend caution due to concerns about exacerbated immune-related adverse events (irAEs) and renal complications, yet real-world data are lacking. Methods: We identified adults with RCC who received pembrolizumab, nivolumab or ipilimumab within the TriNetX Network. Patients with systemic AID formed Cohort A, while Cohort B comprised matched controls without AID. Propensity score matching (1:1) was performed for demographics, comorbidities, RCC stage, baseline renal function, and other variables. Outcomes included immune-related toxicities, renal events, and clinical outcomes. Kaplan-Meier and risk analyses were performed, excluding patients with prior outcomes. Results: After matching, 244 patients per group were analyzed, with a mean age of 65 years and 66% male. The rates of immune-related adverse outcomes were similar between cohorts, including steroid initiation (54% in AID vs 62% in controls), colitis (17.1% vs 17.6%), immune hepatitis (7.1% vs 9.5%), adrenalitis (4.2% vs 4.2%), hypothyroidism (10.4% vs 10.9%), hyperthyroidism (2.2% vs 2.7%), and peripheral neuropathy (1.2% vs 1.5%). Hypophysitis occurred more frequently in the autoimmune cohort (4.1% vs 0%), though absolute event rates were low. Renal outcomes, including AKI (36.8% vs 35.7%), dialysis (4.3% vs 4.4%), progression to advanced CKD (8.3% vs 10.6%), and elevated BUN (14.4% vs 16.8%), were also comparable between groups. clinical outcomes, such as cardiac arrest (4.2% vs 4.1%), septic shock (7.9% vs 4.2%), all-cause mortality (41.8% vs 39.8%), hospitalization (75.8% vs 79.5%), and outpatient visits (89.0% vs 93.0%), did not differ significantly between groups, all p-values being non-significant. Conclusion: In this study, RCC patients with AID receiving ICIs experienced similar rates of immune-related, renal, and clinical adverse outcomes as controls. Except for a higher rate of hypophysitis in the AID cohort, there was no increased risk of major toxicity. These findings address a critical gap in the literature and suggest that, with appropriate patient selection and monitoring, ICI therapy may be considered in RCC patients with autoimmune disease.