Abstract
Background: Because lenvatinib is well known to induce proteinuria by blocking the vascular endothelial growth factor (VEGF) pathway, renal function is a concern for patients with long-term administration of lenvatinib. The long-term effects of lenvatinib on renal function in patients with advanced differentiated thyroid carcinoma (DTC) were analyzed. Method: This study involved 40 DTC patients who continued lenvatinib therapy for ≥6 months. Estimated glomerular filtration rate (eGFR) was calculated as an indicator of renal function. The temporal course of eGFR, effects of baseline eGFR on eGFR changes, and factors affecting renal impairment were investigated. Results: The overall cohort showed sustainable decreases in eGFR, with decreased values of 11.4, 18.3, and 21.0 mL/min/1.73 m2 at 24, 36, and 48 months after starting treatment, respectively. No differences in eGFR decrease every 6 months were seen for three groups classified by baseline eGFR ≥90 mL/min/1.73 m2 (n=6), ≥60 by <90 mL/min/1.73 m2 (n=26), and ≥45 but <60 mL/min/1.73 m2 (n=8). Grade 3 proteinuria was associated with decline in eGFR (p=0.0283). Long observation period was also associated with a decrease in eGFR (p=0.0115), indicating that eGFR may decrease in a time-dependent manner. Conclusion: Lenvatinib can induce decline in eGFR, especially with treatment duration >2 years, regardless of baseline eGFR. Proteinuria is a risk factor for decline in eGFR. Patients who start lenvatinib with better renal function show a renal reserve capacity, prolonging clinical outcomes. Decision-making must balance the benefits of lenvatinib continuation with allowed harm.
Psychological distress during lactation period induces long term effects in a sex-dependent manner in mice
