New-onset nephrotic syndrome and acute kidney injury after cabozantinib

Abstract

Introduction: Renal adverse events related to receptor tyrosine kinase inhibitors (RTKIs) have been reported, including elevated creatinine levels, electrolyte abnormalities, elevated blood pressure, and proteinuria. Cabozantinib is a RTKI approved for patients with renal cell carcinoma (RCC), who have failed other lines of treatment. Here we report a case of nephrotic syndrome with biopsy-proven podocytopathy shortly after starting cabozantinib. Case description: An 80-year-old white man with stage IV metastatic papillary RCC was started on cabozantinib for progressive RCC. At baseline he had chronic kidney disease with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 (serum creatinine 1.3 mg/dL) and a urine microalbumin to creatinine ratio of 5.4 mg/g creatinine. Approximately 3 weeks after starting cabozantinib the patient presented to the hospital with nausea, vomiting, fevers, and failure to thrive and was found to have acute kidney injury (creatinine peaked at 6.0 mg/dL) and nephrotic-range proteinuria, for which a kidney biopsy was performed. Biopsy demonstrated acute tubular necrosis and podocytopathy with 90% foot process effacement. Discussion: Cabozantinib is a recently approved RTKI, which has previously been demonstrated to cause thrombotic micro-angiopathy (TMA). Podocytopathies have been demonstrated by biopsy in cases of other RTKI induced proteinuria, but to our knowledge this is the first case which demonstrates isolated podocytopathy temporally associated with the initiation of cabozantinib.