Clinical Characteristics of AKI Associated with Chimeric Antigen Receptor T Cell (CAR-T) Therapy in Kyoto University Hospital

Background: CAR-T therapy was approved in 2017 for the treatment of several refractory hematologic tumors and is expected to be expanded to other hematologic and solid tumors in the future. Side effects include cytokine release syndrome (CRS) and, in severe cases, multiple organ failure. However, evidence of AKI associated with CAR-T cell therapy is limited. Methods: We investigated the incidence of CRS and AKI, cause of AKI, background factors of patients, and renal prognosis in 131 patients treated with CAR-T therapy between December 2019 and December 2023 at our hospital. A two-sample t-test was performed for continuous variables, and the chi-square test for categorical variables. In addition, the renal pathology of two autopsies after AKI due to CRS was examined to reveal the pathogenesis of AKI due to CRS. Results: CRS occurred in 121 cases (92.4%), and AKI occurred in 7 cases (5.3%, Stage 1: 1 case, Stage 2: 1 case, Stage 3: 5 cases). The causes of AKI were CRS (6 cases) and tumor lysis syndrome (1 case). The number of previous chemotherapy regimens, poor response to primary disease, CRS severity, poor response after CAR-T therapy, and higher basal lactate dehydrogenase (LDH), C-reactive protein (CRP), and ferritin levels were significantly associated with AKI development. Four patients recovered to baseline renal function after AKI, one patient remained with renal impairment, and two patients died. Renal pathology of autopsy cases showed glomerular and peritubular capillary congestion, interstitial edema, and acute tubular necrosis without glomerular nephritis. Conclusion: In our study, higher tumor volume was considered a risk factor for AKI. Evaluation of tumor volume in the primary disease, such as measurement of serum markers or tumor size on a CT scan, may be useful in predicting the development of AKI after CAR-T therapy. Approximately 70% of AKI cases were stage 3, but about half of the patients recovered to baseline renal function, suggesting that renal prognosis is relatively good when the patient survives. The main pathological features of AKI associated with CRS are interstitial edema, and acute tubular necrosis, indicating that hemodynamic changes could induce AKI associated with CAR-T therapy.