Abstract
Lenvatinib, a multi-targeted tyrosine kinase inhibitor (TKI), is widely used in the treatment of radioactive iodine-refractory thyroid carcinoma, including poorly differentiated subtypes. While its clinical efficacy is well documented, significant adverse events, such as proteinuria and renal dysfunction, may confine the treatment. This report describes a case of a 77-year-old man with poorly differentiated thyroid carcinoma who developed nephrotic-range proteinuria and progressive renal impairment shortly after initiating lenvatinib. Renal biopsy revealed histological features consistent with glomerular microangiopathy (GMA), including mesangiolysis, endothelial swelling, and double-contour formation of glomerular capillaries. Following the temporary discontinuation of lenvatinib, proteinuria and renal function gradually recovered. However, due to the drug's significant antitumor effects, lenvatinib was restarted at a reduced dose and titrated cautiously. Despite persistent proteinuria and a gradual decline in renal function, treatment was continued for 43 months. Lenvatinib was ultimately discontinued when serum creatinine reached 4.53 mg/dL. After cessation, renal function stabilized without the need for renal replacement therapy, but the patient died of progressive metastatic disease. This case highlights the risk of lenvatinib-induced GMA and the importance of renal biopsy in confirming the diagnosis. It also demonstrates the complex clinical decision-making required to balance oncologic efficacy with renal safety. Careful dose adjustment and close monitoring of renal parameters are essential in patients who develop nephrotoxicity during TKI therapy. This report adds to the growing evidence on lenvatinib-induced nephropathy and underscores the need for individualized treatment strategies in patients with advanced thyroid carcinoma.