Nephrotic-Range Proteinuria and AKI Following Chimeric Antigen Receptor T Cell Therapy for Multiple Myeloma

Introduction: Chimeric Antigen Receptor T (CAR T) Cell Therapy is a form of immunotherapy where autologous T cells are genetically engineered to express antigens that target cancer cells. It has been approved for various malignancies such as lymphomas, leukemias, multiple myeloma and is helpful in relapsed or refractory disease. Kidney complications from CAR-T can result from hemodynamic shifts with cytokine release syndrome, tumor lysis syndrome and macrophage activation syndrome. We present a case of a patient who developed acute kidney injury and nephrotic range proteinuria after undergoing CAR-T for treatment of multiple myeloma. Case Description: The patient is a 57 year old male with IgG kappa multiple myeloma with high light chain burden with progressive disease on multiple regimens prior to admission for CAR-T. He had mild cytokine release syndrome after CAR-T infusion which was treated with IL-6 inhibition and corticosteroids and was discharged with normal kidney function. Two weeks later, he presented with fever and hypotension and had iodinated contrast with CT imaging. Labs revealed serum Cr trending to 2.75mg/dL from baseline of 1 and urine protein-to-creatinine ratio of 35.21, which was confirmed with repeat spot measurement and 24 hour urine collection. Kidney biopsy showed acute tubular ibjury as well as diffuse foot process effacement. Discussion: This case highlights a rare kidney response in patients receiving CAR-T therapy. While the ATI may have been contrast-related, the severe proteinuria and diffuse foot process effacement is more typical of minimal change disease. Cytokine storm with CAR-T may result in proteinuria, but this patient had mild CRS and the proteinuria was delayed. As MCD is an immune-mediated disease, this case raises the possibility that CAR-T therapy may result in off-target, off-tumor kidney toxicity potentially by autoantibody against podocyte proteins.