Chronic Limited Renal Thrombotic Microangiopathy and Podocytopathy Secondary to Cabozantinib

Introduction: Thrombotic microangiopathy (TMA) is a condition characterized by thrombi in the microcirculation, often leading to kidney dysfunction. Podocytopathy is caused by damage to podocytes which are essential cells in the kidney’s filtration barrier. Cabozantinib, a tyrosine kinase inhibitor, is linked to such renal complications. This case report presents such a case of chronic limited renal TMA and podocytopathy secondary to cabozantinib. Case Description: Patient is a 79 year old male with a history of hepatocellular carcinoma (HCC), type 2 diabetes mellitus, and a history of hepatitis C, cirrhosis who presented to the Nephrology clinic for nephrotic syndrome. Briefly, he was diagnosed with HCC based on MRI imaging and elevated alpha-fetoprotein. He underwent treatment with Y-90 with some benefit, and was subsequently started on atezolizumab and bevacizumab. His course was complicated upon interval development of lung adenocarcinoma, and he had disease progression of his HCC. Both malignancies were thought to be covered on this regimen, though the patient developed proteinuria and hypoalbuminemia so bevacizumab was held and cabozantinib was added to atezolizumab. However, his proteinuria was noted to worsen. Workup included normal complement levels, kappa/lambda light chains, serum protein electrophoresis, negative double stranded DNA, but positive ANA. This prompted a kidney biopsy, which revealed changes consistent with chronic phase of TMA, and ultrastructural features of podocytopathy (Figure 1). It was determined that cabozantinib was causing his worsening proteinuria and TMA with podocytopathy, and thus his treatment regimen has changed to lenvatinib and pembrolizumab. Discussion: Cabozantinib is a TKI used in a variety of malignancies, and chronic limited renal TMA and podocytopathy are significant but rarely documented complications of this chemotherapeutic agent [1]. Cabozantinib inhibits angiogenesis, and in this manner, may disrupt vascular integrity in the kidneys, thus inducing TMA and podocyte injury [2]. Podocytopathy compromises the glomerular filtration barrier, causing a nephrotic syndrome type presentation in [3].This case thus illustrates the importance of vigilant monitoring for renal side effects in patients initiated on cabozantinib so this medication can be dose-adjusted or discontinued so as to prevent irreversible renal impairment.