The Intersection between Chimeric Antigen Receptor T Cell (CAR-T) Therapy and the Kidneys: A Multicenter Study of Outcomes

Background: Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized the treatment of refractory hematologic malignancies. Despite its remarkable efficacy, CAR-T therapy is associated with serious adverse effects, including electrolyte abnormalities and acute kidney injury (AKI). Methods: This study aims to determine the incidence of electrolyte abnormalities and AKI in patients receiving CAR-T therapy. Additionally, we assessed survival outcomes following these events and compared risk differences in patients with and without AKI. We conducted a retrospective multi-center cohort study using the TriNetX database. We identified 3,537 patients who received CAR-T therapy and subsequently developed electrolyte abnormalities or AKI. Survival following these events was also evaluated Results: The incidences of abnormalities and respective survival properties were as follows: - Hyponatremia:16.5%, survival probability: 78.9%. - Hypernatremia: 3.8%, survival probability: 94.9%. - Hypocalcemia: 7%, survival probability: 90.4% - Hypercalcemia: 6.6%, survival probability: 91.2%. - Hypophosphatemia: 14.7%, survival probability: 80.7%. - Hyperphosphatemia: 1.5%, survival probability: 80.5%. - AKI: 22.4%, survival probability: 70.4%. Compared with the non-AKI cohort, the AKI group had a higher incidence of: - Hyponatremia (24% vs. 14%), associated with lower survival (67.7% vs. 83.1%); - Hypernatremia (8.7% vs. 1.3%), associated with lower survival (88.2% vs. 98.2%); - Hypocalcemia (11.7% vs. 5.8%), associated with lower survival (84.2% vs. 93.2%); - Hypercalcemia (11.6% vs. 3.6%), associated with lower survival (84.5% vs. 95.2%). - Hypophosphatemia (25% vs. 12.2%), associated with lower survival (66% vs. 85.1%); - Hyperphosphatemia (25.5% vs. 12.2%), with similar survival Mortality was higher in patients with AKI following CAR-T therapy, with a risk of 39.5% compared to 18.2% in patients without AKI (RR 0.461, 95% CI 0.415-0.512). Conclusion: CAR-T therapy is associated with multiple electrolyte derangements and a significant incidence of AKI. These imbalances correlate with increased mortality risk. Patients who develop AKI are at higher risk of electrolyte abnormalities and have lower survival probabilities. Overall, careful monitoring and management of electrolyte disturbances in patients undergoing CAR-T therapy are crucial.