Self-limited membranous nephropathy after intravitreal bevacizumab therapy for age-related macular degeneration

BACKGROUND Monoclonal antibodies targeting vascular endothelial growth factor (VEGF), such as bevacizumab, are administered intravitreally for the treatment of wet or exudative age-related macular degeneration (ARMD). Systemic use of bevacizumab has been linked to a wide range of renal adverse effects including proteinuria and hypertension. CASE PRESENTATION We present the case of a 77-year-old Caucasian male with a past medical history of hypertension, vitamin D deficiency and paroxysmal atrial fibrillation who presented to primary care clinic with a 2-week history of bilateral lower extremity edema, 2 months after completing four monthly intravitreal injections of bevacizumab for ARMD. Examination was remarkable for blood pressure of 187/91 mm Hg and severe bilateral lower extremity edema. Work up revealed unremarkable complete blood count (CBC), comprehensive metabolic panel (CMP), lipid panel, and echocardiography, except for 491 mg/dL albuminuria. Metoprolol and furosemide were added to hydrochlorothiazide and lisinopril. Work up by nephrology consult team five months later was notable for a urinalysis revealing 3 red blood cells/high power field (RBC/HPF), 24-hour urine protein of 8.6 g, and serum creatinine of 1.2 mg/dL. Viral hepatitis panel, total complement activity (CH50), C3, C4, anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), serum and urine protein electrophoresis were all unremarkable. Renal biopsy was consistent with membranous nephropathy. Age-appropriate cancer screening was negative. Random urine protein-to-creatinine ratio declined to 2 g/g and then to 0.56 g/g at 7 and 10 months follow up, respectively. Serum blood urea nitrogen (BUN) and creatinine remained normal throughout the course of illness and patient did not require any immunosuppressive treatment. CONCLUSIONS The wide range of nephrotoxicity after systemic bevacizumab has been well documented. Our case describes a self-limited biopsy-proven membranous nephropathy after intravitreal bevacizumab injections.