title: All anti-vascular endothelial growth factor drugs can induce 'pre-eclampsia-like syndrome': a RARe study.
abstract: BACKGROUND
  Specific therapies that target vascular endothelial growth factor (VEGF) and its receptors have improved the survival of patients with metastatic cancers, but can induce side effects. Renal side effects (proteinuria, hypertension and renal failure) are underestimated.
  
  
  METHODS
  The French RARe (Reins sous traitement Anti-VEGF Registre) study collects data on patients with cancer who had a renal biopsy because of major renal side effects during treatment with anti-VEGF drugs.
  
  
  RESULTS
  We collected 22 renal biopsies performed 16.2±10.6 months after the beginning of treatment; of which 21 had hypertension, mean proteinuria was 2.97±2.00 g/day and mean serum creatinine, 134±117 µmol/L. Thrombotic microangiopathy (TMA) was observed in 21 biopsy specimens, sometimes associated with acute tubular necrosis (ATN; n=4). TMA histological lesions were more important than the biological signs of TMA could suggest. Patients with ATN of >20% had higher serum creatinine levels than those with only TMA (231 versus 95 µmol/L). Nephrin, podocin and synaptopodin were variably down-regulated in all renal biopsies. VEGF was down-regulated in all glomeruli.
  
  
  CONCLUSIONS
  This study underlines the importance of regular clinical and biological cardiovascular and renal checking during all anti-VEGF therapies for cancer for early detection of renal dysfunction. Collaboration between oncologists and nephrologists is essential. In such cases, renal biopsy might help in appreciating the severity of the renal lesions and after multidisciplinary discussion whether or not it is safe to continue the treatment.
authors.affiliation: CHU Rennes, Service de Néphrologie, Rennes, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Vigneau
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Lorcy
authors.forename: Thibault
authors.initials: T
authors.lastname: Dolley-Hitze
authors.forename: Florence
authors.initials: F
authors.lastname: Jouan
authors.forename: Yannick
authors.initials: Y
authors.lastname: Arlot-Bonnemains
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laguerre
authors.forename: Gregory
authors.initials: G
authors.lastname: Verhoest
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Goujon
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Belaud-Rotureau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001706:Biopsy; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D007150:Immunohistochemistry; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011758:Pyrroles / Q000009:adverse effects* / Q000627:therapeutic use; D012042:Registries; D012189:Retrospective Studies; D000077210:Sunitinib; D013577:Syndrome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib
keywords: anti-VEGF; drug side effects; kidney biopsy; pre-eclampsia