Abstract
Introduction
Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used in patients with cardiovascular disease, diabetes, and hypertension, with well-established mortality benefits. However, concerns remain about their potential to worsen kidney function. In patients with hematologic malignancies undergoing treatment, the risk of tumor lysis syndrome (TLS) and acute kidney injury (AKI) is already elevated. This study examines the impact of concurrent ACEi/ARB use on the incidence of TLS, AKI, and rasburicase utilization in this high-risk population.
Methods
The TriNetX Research Network was used to identify patients aged 18 years or older with hematologic malignancies who initiated chemotherapy between 2015 and 2024. The following malignancies were included due to their established risk for TLS: Burkitt lymphoma, acute lymphoblastic leukemia, acute myeloblastic leukemia, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, adult T-cell lymphoma/leukemia, lymphoblastic lymphoma, and peripheral T-cell lymphoma. Patients were divided into those who received an ACEi or ARB within 30-days of chemotherapy initiation, and those who did not. Propensity score matching was conducted using 1:1 nearest-neighbor matching based on age, sex, race, comorbidities, baseline laboratory values, and history of nephrotoxic medication use. TLS, AKI, and rasburicase use were assessed within the first month following chemotherapy initiation. Analyses were performed within the TriNetX platform using the measures of association function to estimate risk differences, relative risk (RR), and 95% confidence intervals (CIs).
Results
A total of 17,583 patients receiving ACEi/ARBs within 30 days of chemotherapy initiation were identified, compared to 111,600 patients who were not. After propensity matching, both cohorts included 17,583 patients. After removing patients with a prior history of TLS, AKI, or rasburicase use from each respective analysis, 1.9% of patients in the ACEi/ARB group developed TLS, compared to 1.3% in the control group, with a risk difference of 0.6% and a RR of 1.5 (95% CI: 1.5–1.8; p < 0.001). The incidence of AKI was also higher in the ACEi/ARB group (7.8%) compared to the control group (5.0%), with an RR of 1.6 (95% CI: 1.4–1.7; p < 0.001). Similarly, rasburicase use was greater in the ACEi/ARB group (3.1%) versus the control group (2.2%), with an RR of 1.4 (95% CI: 1.2–1.6; p < 0.001).
Conclusion
This study highlights the clinical impact of ACEi/ARB use in patients with hematologic malignancies undergoing treatment. Although TLS is relatively uncommon, it can be life-threatening, and its incidence is significantly increased with concurrent ACEi/ARB use. This has important implications not only for patient outcomes but also for the financial burden related to supportive care, including rasburicase use. Clinicians should carefully consider the risks and benefits of continuing ACEis/ARBs during the acute treatment phase, particularly when the risk of TLS is highest.
