Abstract
BackgroundBecause lenvatinib is well known to induce proteinuria by blocking the vascular endothelial growth factor (VEGF) pathway, renal function is a concern 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.MethodThis 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.ResultsThe 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), < 90 but ≥60 mL/min/1.73 m2 (n = 26), or < 60 but ≥45 mL/min/1.73 m2 (n = 8). Grade 3 proteinuria was associated with declines in eGFR (p = 0.0283). Long observation period was also associated with decreases in eGFR (p = 0.0115), indicating that eGFR may decrease in a time-dependent manner.ConclusionLenvatinib can induce declines in eGFR, particularly with treatment duration > 2 years, regardless of baseline eGFR. Proteinuria is a risk factor for declines in eGFR. Patients who start lenvatinib with better renal function show a renal reserve capacity, prolonging clinical outcomes. Decision-making protocols must balance the benefits of lenvatinib continuation with acceptable risks of harm.
Highlights
Lenvatinib is an agent that shows strong tumor suppression, targeting multiple receptors including vascular endothelial growth factor receptor (VEGFR)-1 to − 3 [1, 2]
No differences in Estimated glomerular filtration rate (eGFR) decrease every 6 months were seen for three groups classified by baseline eGFR ≥90 mL/min/1.73 m2 (n = 6), < 90 but ≥60 mL/min/ 1.73 m2 (n = 26), or < 60 but ≥45 mL/min/1.73 m2 (n = 8)
Grade 3 proteinuria was associated with declines in eGFR (p = 0.0283)
Summary
Lenvatinib is an agent that shows strong tumor suppression, targeting multiple receptors including vascular endothelial growth factor receptor (VEGFR)-1 to − 3 [1, 2]. Iseki et al reported the ultimate incidences of ESRD among screened individuals with a 17-year follow-up period as 0.2, 1.4, 7.1, and 15.4% among proteinuria-negative, 1+, 2+, and 3+ cases, respectively [9]. This suggests the importance of further investigation of renal outcomes among patients with proteinuria. Because lenvatinib is well known to induce proteinuria by blocking the vascular endothelial growth factor (VEGF) pathway, renal function is a concern 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
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