Prospective evaluation of CAR-T cell therapy-related proteinuria and kidney dysfunction

Background The nephrotoxicity of chimeric antigen receptor T-cell (CAR-T) therapy has been reported, yet data on urinary abnormalities remain limited. This study aimed to characterize proteinuria, acute kidney injury (AKI), and associated electrolyte disorders in patients treated with CAR-T therapy. Methods A prospective analysis was conducted on 63 patients treated with CAR-T therapy between June 2020 and December 2023. Blood tests were collected daily during hospitalization and a first morning urine void was collected on day of infusion (D0), +7 (D7) and +14 (D14). Results During the study period, 12 patients (19 %) developed AKI. The median urine protein-to-creatinine ratio (uPCR) increased significantly from 0.12 0.17 g/g on D0 to 0.39 g/g on D7, returning to baseline levels at D14. Proteinuria greater than 0.5 g/g was detected in 38% of patients at day +7. Patients with AKI before D7 had higher proteinuria than patients without AKI or AKI after D7. Proteinuria was associated with higher levels of lactate dehydrogenase (LDH), interleukin-6 levels and cytokine release syndrome (CRS) grade ≥3. Patients with higher proteinuria had more progression of hematological disease and increased mortality in the first year. Additionally, 60 patients (95%) experienced at least one electrolyte disorder, hypophosphatemia being the most frequent. Higher proteinuria was associated with lower levels of phosphorus, potassium and sodium. Conclusions CAR-T therapy is associated with transient renal adverse effects, including proteinuria, AKI and electrolyte disorders. Systemic inflammation-mediated tubular injury contributed to these adverse effects. These findings enhance our understanding of CAR-T therapy nephrotoxicity. Proteinuria levels at D0 may help predict the risk of be associated with disease progression and mortality within the first year.