Sunitinib is an orally administered inhibitor of tyrosine kinase targeting vascular endothelial growth factor receptors (VEGFRs) and has become essential for treating metastatic renal cell carcinoma. Recently, several cases have been reported which showed proteinuria and kidney dysfunction during anti-VEGF therapy. Although previous reports indicated that this side effect is reversible, it is not well understood. We report here the case of a 52-year-old man who presented with hypertension, nephrotic syndrome, and renal dysfunction during sunitinib treatment. Sunitinib was discontinued, but renal function recovery was limited. A renal biopsy was performed because sunitinib was again required and pathological examination was needed. The renal biopsy showed exacerbation of diabetic nephropathy. After medical treatment, the patient’s blood pressure was controlled and serum creatinine level decreased. We considered that the patient could tolerate sunitinib at a minimum effective dose, 25 mg/day. Previous reports suggest that all anti-VEGF drugs may share a common risk for developing renal adverse events, such as thrombotic microangiopathy. Sunitinib should not be restarted if thrombotic microangiopathy is observed. The present case suggests that renal biopsy would be recommended when treatment options and prognosis might be influenced by the actual histological diagnosis.