Endogenous Antiangiogenic Factors in Chronic Kidney Disease: Potential Biomarkers of Progression

Int J Mol Sci. 2018 Jun 24;19(7):1859. doi: 10.3390/ijms19071859.

Abstract

Chronic kidney disease (CKD) is a major global health problem. Unless intensive intervention is initiated, some patients can rapidly progress to end-stage kidney disease. However, it is often difficult to predict renal outcomes using conventional laboratory tests in individuals with CKD. Therefore, many researchers have been searching for novel biomarkers to predict the progression of CKD. Angiogenesis is involved in physiological and pathological processes in the kidney and is regulated by the balance between a proangiogenic factor, vascular endothelial growth factor (VEGF)-A, and various endogenous antiangiogenic factors. In recent reports using genetically engineered mice, the roles of these antiangiogenic factors in the pathogenesis of kidney disease have become increasingly clear. In addition, recent clinical studies have demonstrated associations between circulating levels of antiangiogenic factors and renal dysfunction in CKD patients. In this review, we summarize recent advances in the study of representative endogenous antiangiogenic factors, including soluble fms-related tyrosine kinase 1, soluble endoglin, pigment epithelium-derived factor, VEGF-A165b, endostatin, and vasohibin-1, in associations with kidney diseases and discuss their predictive potentials as biomarkers of progression of CKD.

Keywords: PEDF; VEGF-A; VEGF-A165b; chronic kidney disease; endogenous antiangiogenic factors; endostatin; soluble Flt-1; vasohibins.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inducing Agents / chemistry
  • Angiogenesis Inducing Agents / metabolism
  • Angiogenesis Inhibitors / genetics*
  • Angiogenesis Inhibitors / metabolism
  • Animals
  • Biomarkers / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Disease Progression
  • Endostatins / genetics
  • Endostatins / metabolism
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Gene Expression Regulation
  • Humans
  • Kidney Failure, Chronic / diagnosis*
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / pathology
  • Mice
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / metabolism
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / diagnosis*
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / pathology
  • Serpins / genetics*
  • Serpins / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • Biomarkers
  • Cell Cycle Proteins
  • Endostatins
  • Eye Proteins
  • Nerve Growth Factors
  • Serpins
  • VASH1 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • pigment epithelium-derived factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1