Acute kidney injury following CAR-T cell therapy: a nephrologist's perspective

Chimeric antigen receptor T (CAR-T) cell therapy, an emerging personalized immunotherapy for various haematologic malignancies, autoimmune diseases and other conditions, involves the modification of patients' T cells to express a chimeric antigen receptor that recognizes tumour or autoimmune cell antigens, allowing CAR-T cells to destroy cancerous and other target cells selectively. Despite remarkable clinical improvements in patients, multiple adverse effects have been associated with CAR-T cell therapy. Among the most recognized adverse effects are cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and tumour lysis syndrome. Even though less recognized, the incidence of acute kidney injury (AKI) ranges from 5 to 33%. The wide range of reported AKI incidence rates might depend on patient population characteristics and comorbidities and specific CAR-T cell therapy features. Even though the exact pathophysiology remains unknown, several key mechanisms, including cytokine release syndrome, tumour lysis syndrome and other factors such as direct renal toxicity of CAR-T cell therapy, conditioning regimens or other medications (e.g. antibiotics), and infectious complications (e.g. sepsis) have been proposed. Risk factors for CAR-T-related AKI include lower baseline glomerular filtration rate, higher rates of allopurinol or rasburicase use, intravenous contrast material exposure, elevated baseline lactate dehydrogenase and grade 3 or higher cytokine release syndrome. Future prospective studies with larger patient populations are needed to gain insights into the pathophysiology of CAR-T-related AKI and, more importantly, to be able to prevent as well as to develop novel and more efficient treatment modalities. In this narrative review, we discuss the underlying pathophysiology, risk factors, potential interventions and future directions related to AKI following CAR-T cell therapy.