Worsening Proteinuria Following Intravitreal Anti-VEGF Therapy for Diabetic Macular Edema

Abstract

Intravitreal antivascular endothelial growth factor (anti-VEGF) therapy is a standard of care for a variety of ophthalmological conditions. While the systemic use of these agents in oncology is well known to induce a number of renal-related adverse effects such as worsening hypertension and proteinuria, the ability of local intravitreal injections to cause similar side effects has traditionally been thought to be unlikely given the lower doses used. In this case report, we describe an 88-year-old woman who developed a sudden worsening of her previously stable proteinuria with the use of bilateral intravitreal bevacizumab injections for diabetic macular edema, with improvement in her proteinuria upon reduction to unilateral therapy. This case report adds to the growing body of literature that suggests that local anti-VEGF therapy may have the potential to induce adverse systemic effects, and clinicians who care for these patients should remain vigilant to the development of potential renal-related toxicity.

Nephrotoxicity induced by intravitreal vascular endothelial growth factor inhibitors: emerging evidence

“…21 The most recent study by Kenworthy et al reports worsening of chronic stable proteinuria that was attributed to diabetic nephropathy after intravitreal injection of bevacizumab. 70 A recent retrospective study of 69 patients did not report acute kidney injury after a short-term follow-up of 7 to 30 days after intravitreal injections of bevacizumab, aflibercept, or ranibizumab. 71 Levels of anti-VEGF agents and proteinuria were not monitored.…”

Thrombotic Microangiopathy and Acute Kidney Injury Induced After Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors VEGF Blockade-Related TMA After Intravitreal Use

“…There are three more in this case series and one more under review. In total, there are 30 known cases demonstrating systemic toxicity after intravitreal VEGF inhibitor injections (2,4,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). See Table 1.…”

“…Other TMA presentations after intravitreal VEGF blockade in the literature are reviewed in Table 1 (4,32,39,42,43,46) along with other published evidence (2,4,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). Other glomerular lesions such as collapsing glomerulopathy have been associated with intravitreal anti-VEGF agents as well (2,4).…”

Membranoproliferative glomerulonephritis after intravitreal vascular growth factor inhibitor injections: A case report and review of the literature

“…24 Our literature review revealed 26 cases of severe renal injuries after intravitreal anti-VEGF injections that required nephrological management (Table 1). [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] These cases were reported in 2011-2021, 69% were male, 81% were older than 50 years and DR/DME was the most common indication (62%) followed by nAMD (27%). Most received bevacizumab alone (58%) or followed by either ranibizumab and/or aflibercept (23%).…”