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.