Sunitinib-induced nephrotic syndrome and irreversible renal dysfunction

Sunitinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs), has become essential for treating imatinib-resistant malignant gastrointestinal stromal tumor. Recently, several cases have been reported that showed proteinuria and kidney dysfunction to be associated with anti-VEGF therapy. Although previous reports indicated that this side-effect is reversible, it is not well understood. We present here the case of a 72-year-old man who presented with nephrotic syndrome and renal dysfunction 6 months after administration of sunitinib. Sunitinib was discontinued, and nephrotic syndrome remitted spontaneously, but renal function recovery was limited. Nine months later, a renal biopsy was performed because sunitinib was again required and pathological examination was needed. The renal biopsy showed marked endothelial cell injury with focal segmental glomerulosclerosis and accelerated VEGF expression by podocytes. Sunitinib was then given at a reduced dose. Kidney dysfunction and nephrotic syndrome are rare but serious complications of sunitinib. The present case suggests that long-term treatment with a high dose of sunitinib can cause irreversible renal dysfunction, and that low-dose treatment makes these side-effects manageable.