Nephrotic syndrome associated with ramucirumab therapy

Abstract Ramucirumab is a human immunoglobulin G1 monoclonal antibody that binds to vascular endothelial growth factor receptor 2 and is used for the treatment of metastatic or inoperable gastric, colorectal, and non-small cell lung cancers. However, ramucirumab can result in renal adverse events, including nephrotic syndrome, and the clinical course of this event is unclear. This study aimed to investigate the clinical course and pathological findings of patients with nephrotic syndrome after ramucirumab treatment. We evaluated 5 patients with malignancies (2 cases of gastric cancer and 3 cases of colorectal cancer) who developed nephrotic syndrome during treatment with ramucirumab. Two patients were diagnosed based on renal biopsy. We investigated the relationship between ramucirumab treatment and clinical courses, pathological findings, and renal outcomes. Four of 5 patients developed nephrotic syndrome after 1 or 2 doses of ramucirumab. All patients had hypertension, and 2 of 5 patients had renal dysfunction, defined as an increase in serum creatinine levels of ≥50% or ≥0.3 mg/dL. The 2 renal biopsy samples revealed a diffuse glomerular basement membrane double contour, intracapillary foam cell infiltration, and partial foot process effacement. Early drug discontinuation and antihypertensive therapy improved proteinuria, renal dysfunction, and hypertension in all patients. Nephrotic syndrome is a renal adverse event observed in cancer patients after ramucirumab treatment. We suggest that urinalysis, renal function, and blood pressure should be closely monitored in patients undergoing ramucirumab treatment, and treatment should be discontinued if renal adverse events are detected.