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Thrombotic Microangiopathy with Severe Proteinuria Induced by Lenvatinib for Radioactive Iodine-Refractory Papillary
Yasuko Hyogo1, Naomi Kiyota1,2, Naoki Otsuki3
1Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Abstract:
Standard therapy for radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) is multi-targeted kinase inhibitors (m-TKIs), represented by sorafenib and lenvatinib. One of the main target molecules of m-TKIs is vascular endothelial growth factor receptor (VEGF-R). m-TKIs are known to cause adverse reactions such as hypertension and proteinuria as a class effect. In particular, proteinuria is thought to result from vascular endothelial damage and podocytopathy in glomeruli, and the development of thrombotic microangiopathy (TMA) has been reported for VEGF inhibitors. We encountered a patient with RAI-refractory (RR) papillary thyroid carcinoma (PTC) who developed proteinuria and renal dysfunction due to lenvatinib. Renal biopsy demonstrated that these changes were caused by TMA. To our knowledge, this is the first reported case of TMA due to lenvatinib in a Japanese patient with RR-PTC. A 70-year-old woman developed proteinuria, renal impairment and hypertension while receiving lenvatinib for RR-PTC. Her proteinuria and renal damage continued to worsen despite dose reductions and dose interruptions. Renal biopsy was consistent with the chronic type of TMA. These findings indicate that TMA is a possible cause of proteinuria due to lenvatinib, as has been reported for the VEGF inhibitors.
Insights
Lenvatinib, a multi-targeted kinase inhibitor, can cause thrombotic microangiopathy (TMA), leading to proteinuria and renal dysfunction in patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). This case highlights TMA as a potential adverse effect of lenvatinib.
Area of Science:
- Nephrology
- Oncology
- Pharmacology
Background:
- Radioactive iodine-refractory differentiated thyroid cancer (DTC) is typically treated with multi-targeted kinase inhibitors (m-TKIs) like lenvatinib.
- Vascular endothelial growth factor receptor (VEGF-R) is a key target of these m-TKIs.
- m-TKIs are associated with adverse effects including hypertension and proteinuria, potentially due to vascular endothelial damage.
Observation:
- A 70-year-old Japanese woman with RAI-refractory papillary thyroid carcinoma (PTC) developed proteinuria, renal impairment, and hypertension during lenvatinib treatment.
- Despite dose adjustments, her proteinuria and renal damage persisted.
- Renal biopsy revealed chronic thrombotic microangiopathy (TMA).
Findings:
- This case is the first reported instance of lenvatinib-induced TMA in a Japanese patient with RAI-refractory DTC.
- The renal biopsy findings confirmed TMA as the cause of proteinuria and renal dysfunction.
- VEGF inhibitors, including lenvatinib, are implicated in the development of TMA.
Implications:
- Thrombotic microangiopathy (TMA) should be considered a potential cause of proteinuria and renal dysfunction in patients treated with lenvatinib for DTC.
- This finding underscores the importance of monitoring renal function in patients receiving VEGF-targeted therapies.
- Further research may be needed to elucidate the precise mechanisms and management strategies for lenvatinib-induced TMA.
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