title: Intravitreal Antivascular Endothelial Growth Factor Therapy May Induce Proteinuria and Antibody Mediated Injury in Renal Allografts.
abstract: BACKGROUND
  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.affiliation: 1 Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. 2 Department of Laboratory Medicine and Anatomic Pathology, Mayo Clinic, Rochester, MN. 3 The William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN.
authors.forename: Wisit
authors.initials: W
authors.lastname: Cheungpasitporn
authors.forename: Fouad T
authors.initials: FT
authors.lastname: Chebib
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Cornell
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Brodin
authors.forename: Samih H
authors.initials: SH
authors.lastname: Nasr
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Schinstock
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stegall
authors.forename: Hatem
authors.initials: H
authors.lastname: Amer
mesh_terms: D000368:Aged; D064591:Allografts; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects; D001706:Biopsy; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D006084:Graft Rejection / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D006801:Humans; D058449:Intravitreal Injections; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D016030:Kidney Transplantation; D008268:Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D011507:Proteinuria / Q000139:chemically induced* / Q000175:diagnosis; D000069579:Ranibizumab / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab