Intravitreal Antivascular Endothelial Growth Factor Therapy May Induce Proteinuria and Antibody Mediated Injury in Renal Allografts.

Abstract

INTRODUCTION:

Systemic adverse effects of intravenous antivascular endothelial growth factor (VEGF) therapy include: hypertension, proteinuria, renal failure, and thrombotic microangiopathy. Intravitreal therapy with these agents is generally believed to be safe.

METHODS:

We report 2 cases of renal transplant recipients who developed significant allograft dysfunction after the initiation of intravitreal anti-VEGF therapy.

RESULTS:

The first case is a 67-year-old man with polycystic kidney disease and recipient of a zero-antigen mismatch kidney allograft which developed worsening proteinuria over the first year after transplantation. At 4 months, a biopsy showed only minimal fibrosis and atrophy. At 1 year, an allograft biopsy showed phospholipase A 2 receptor-negative membranous nephropathy. The second patient was a 52-year-old man with tuberous sclerosis who was a recipient of a living related kidney allograft with diminished but stable graft function 16 years from transplantation. After the initiation of intravitreal anti-VEGF therapy, there was an escalating degree of proteinuria. Renal biopsy revealed acute and chronic antibody-mediated rejection with glomerular thrombi and transplant glomerulopathy.

CONCLUSIONS:

These cases, although do not prove causality, point to the need for careful follow-up of renal transplant recipients undergoing intravitreal therapy with anti-VEGF agents. These locally administered agents may play a role in the development of proteinuria and modulate antibody-mediated phenomena. We recommend that in renal transplant recipients undergoing therapy with intravitreal anti-VEGF agents, proteinuria be checked monthly, and there should be a low threshold for performing a biopsy to evaluate for allograft injury.

• Authors: Wisit Cheungpasitporn, Fouad T Chebib, Lynn D Cornell, Michelle L Brodin, Samih H Nasr, Carrie A Schinstock, Mark D Stegall, Hatem Amer
• Journal: Transplantation (Transplantation) Vol. 99 Issue 11 Pg. 2382-6 (Nov 2015) ISSN: 1534-6080 [Electronic] United States
• PMID: 25905984 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Bevacizumab
• Ranibizumab

Topics

• Aged
• Allografts
• Angiogenesis Inhibitors (administration & dosage, adverse effects)
• Bevacizumab (administration & dosage, adverse effects)
• Biopsy
• Fluorescent Antibody Technique
• Glomerulonephritis (chemically induced, diagnosis, immunology, therapy)
• Graft Rejection (chemically induced, diagnosis, immunology, therapy)
• Humans
• Intravitreal Injections
• Kidney (drug effects, immunology, ultrastructure)
• Kidney Transplantation
• Macular Degeneration (diagnosis, drug therapy, metabolism)
• Male
• Microscopy, Electron
• Middle Aged
• Proteinuria (chemically induced, diagnosis)
• Ranibizumab (administration & dosage, adverse effects)
• Risk Factors
• Time Factors
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, metabolism)