Renal thrombotic microangiopathy and nephrotic proteinuria induced by intravitreal injection of aflibercept for diabetic macular edema

BMC Nephrol. 2022 Oct 29;23(1):348. doi: 10.1186/s12882-022-02986-2.

Abstract

Background: Vascular endothelial growth factor inhibitors (VEGFIs) are used to treat malignant neoplasms and ocular diseases by inhibiting angiogenesis. Systemic use of VEGFIs has various side effects, including hypertension, proteinuria, and thrombotic microangiopathy, but adverse events due to intravitreal injection of VEGFIs have not been fully clarified. Although age-related macular degeneration was initially the most common target of intravitreal injection of VEGFIs, it has also been applied sporadically for diabetic macular edema in recent years. Proteinuria following intravitreal injection of VEGFIs would be reversible. In patients with diabetes mellitus (DM), however, it would be difficult to determine whether kidney damage arises from the clinical course of DM or from intravitreal injection of VEGFIs for diabetic macular edema.

Case presentation: A 55-year-old woman with a 20-year history of type 2 DM began intravitreal injection of VEGFI (aflibercept, 2 mg every 4 weeks) for treatment of diabetic macular edema 2 years previously. She presented with leg edema, hypertension, and nephrotic-range proteinuria 14 months after the first injection. Histological examination of renal biopsy specimens revealed diabetic nephropathy with renal thrombotic microangiopathy probably associated with intravitreal injection of VEGFI. The patient's nephrotic syndrome completely improved at 6 months after simply discontinuing aflibercept.

Conclusions: This is a precious report of pathologically investigated renal thrombotic microangiopathy leading to nephrotic syndrome due to intravitreal injection of aflibercept for diabetic macular edema in a patient with type 2 DM. Renal function and proteinuria should be monitored in diabetic patients who receive intravitreal injection of a VEGFI. If kidney damage develops independent of the clinical course of DM during intravitreal injection of a VEGFI, renal biopsy should be performed and intravitreal VEGFI injection discontinued.

Keywords: Aflibercept; Diabetic macular edema; Diabetic nephropathy; Intravitreal injections; Thrombotic microangiopathy; Vascular endothelial growth factor inhibitor.

Publication types

  • Case Reports

MeSH terms

  • Angiogenesis Inhibitors
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Retinopathy* / complications
  • Diabetic Retinopathy* / drug therapy
  • Female
  • Humans
  • Hypertension* / complications
  • Intravitreal Injections
  • Kidney / metabolism
  • Macular Edema* / chemically induced
  • Macular Edema* / drug therapy
  • Middle Aged
  • Nephrotic Syndrome* / complications
  • Proteinuria / chemically induced
  • Proteinuria / complications
  • Proteinuria / drug therapy
  • Recombinant Fusion Proteins / adverse effects
  • Thrombotic Microangiopathies* / chemically induced
  • Thrombotic Microangiopathies* / complications
  • Thrombotic Microangiopathies* / drug therapy
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A

Substances

  • aflibercept
  • Vascular Endothelial Growth Factor A
  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins