Urinary podocyte excretion and proteinuria in patients treated with antivascular endothelial growth factor therapy for solid tumor malignancies

Oncology. 2014;86(5-6):271-8. doi: 10.1159/000360180. Epub 2014 Jun 4.

Abstract

Background: Urinary podocyte excretion (podocyturia) may function as a more specific marker of ongoing glomerular damage. This study sought to analyze the relationship between proteinuria and podocyturia in cancer patients treated with antivascular endothelial growth factor (anti-VEGF) agents.

Methods: Thirty-seven patients treated with anti-VEGF medications were analyzed in a single-institution, cross-sectional study. Podocyte cultures were performed on random urine collections (50-100 ml), and podocytes were identified by positive podocin staining. The corresponding urine samples were analyzed for protein and creatinine (Cr) measurements.

Results: Proteinuria ≥0.5 g/g Cr was found in 30% of the patients (median, 0.12; interquartile range, 0.04-0.86), and 62% had podocyturia. There was a significant difference in the amount of podocyturia between patients with proteinuria ≥0.5 g/g Cr and those with a value <0.5 g/g Cr (median podocyturia, 1.08 cells/mg Cr, range, 0-14.55 vs. 0.03 cells/mg Cr, range, 0-1.64, respectively; p < 0.001). A statistically significant correlation was observed between the cumulative dose of bevacizumab and both proteinuria (r = 0.48, p = 0.004) and podocyturia (r = 0.34, p = 0.045) as well as between proteinuria and podocyturia (r = 0.63, p < 0.001), suggesting that these are mechanistically related.

Discussion: Ongoing podocyte loss may be mechanistically related to the onset and severity of proteinuria in patients treated with anti-VEGF agents.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Bevacizumab
  • Female
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Podocytes / drug effects
  • Podocytes / pathology*
  • Proteinuria / chemically induced
  • Proteinuria / pathology*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab