Abstract A020: Clonal hematopoiesis is associated with acute kidney injury in the context of breast, endometrial, and ovarian cancers

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) has been linked to a higher risk for acute kidney injury (AKI) (Vlasschaert et al. 2024). The high rate of AKI in the context of cancer is often attributed to the administration of nephrotoxic therapies or comorbidities. However, the effect of the interplay between tumor-associated physiologies, treatment, and CHIP on AKI incidence has yet to be characterized. Here, we model the prognostic value of CHIP in predicting AKI across twenty cancer types. Leveraging a single institutional database, we identified 25,189 patients with longitudinal serum creatinine (sCr) measurements, targeted sequencing of paired tumor and blood samples (MSKCC-IMPACT), and well-documented treatment histories. We called AKI events directly from longitudinal measurements by evaluating increases in sCr compared to the average sCr over the prior 90-day window using diagnostic criteria from the Kidney Disease Improving Global Outcomes (KDIGO) consortium. CHIP mutations were called using a previously reported two-tiered filtering schema (Bolton et al. 2020). In our cohort, we found that 26.5% of patients experienced at least one AKI event and 38.0% of patients presented with at least one CHIP mutation. We then performed competing risks analyses over cox proportional hazards models to test for the association of CHIP and time to AKI from the first creatinine measurement, adjusting for age, gender, histories of diabetes, smoking, and prior receipt of cisplatin. CHIP was significantly associated with decreased time to AKI in the context of breast, endometrial, and ovarian cancers (Benjamini-Hochberg-corrected p < 0.05). Subsequent univariate Kaplan-Meier analyses revealed TP53, PPM1D, SRFS2 mutations were associated with 7.50, 9.05, and 9.73-year decreases in median time to AKI (p < 0.01). Our study reveals specific CHIP mutations as prognostic markers for AKI for patients with breast, endometrial, and ovarian cancers. These findings may guide future clinical decision-making regarding treatment for patients with CHIP mutations. Citation Format: Neil Ruthen, Minsoo Kim, Hui Zhuan Tan, Yash Khandwala, A. Ari Hakimi, Alice Won, Ed Reznik, Edgar A Jaimes. Clonal hematopoiesis is associated with acute kidney injury in the context of breast, endometrial, and ovarian cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr A020.