Severe Hypertension and Renal Limited Thrombotic Microangiopathy Associated with Lenvatinib Therapy

Introduction: Lenvatinib is a multikinase inhibitor (MKI) used in the treatment of locally advanced or metastatic differentiated thyroid carcinoma. One of the main target molecules of m-TKIs is vascular endothelial growth factor receptor (VEGF-R). Hypertension (HTN) and Kidney involvement are the most frequent adverse events during treatment with Lenvatinib (LEN). Case illustration: A 64-year-old woman with thyroid cancer (TC) developed a progressive disease. The patient started systemic treatment with Lenvatinib at a dose of 16 mg per day, and the dose was escalated to 24 mg per day. One month after starting Lenvatinib, the patient experienced hypertension (170/90 mmHg). Creatinine increased to 1.23 mg/dl, Urine albumin-creatinine ratio (ACR) was 7340 mg/g. Kidney biopsy was performed and the result shown thrombus in two glomerulus; this is consistent with thrombotic microangiopathy (TMA). Hypertension was controlled with nebivolol 5 mg per day, clonidine 0.15 mg three times a day, irbesartan 300 mg per day, terazosin HCl 4 mg per day and Lercanidipine 20 mg. For three months, we adjusted the dose of lenvatinib to 8 mg per day, and the level of ACR was improved from 7340 mg/g to 2028 mg/g. Kidney function was gradually improved and showed partial recovery after discontinuing the drugs. Discussion: Although lenvatinib showed promising benefits for advanced TC, severe hypertension was reported at a high frequency. Hypertension is the most common AE observed during treatment with MKIs. Drug-induced TMA is estimated to account for 10–13% of all causes of TMA. Conclusion: Severe hypertension, massive proteinuria and TMA were important side effects of lenvatinib.