Elevated soluble VEGF receptor sFlt-1 correlates with endothelial injury in IgA nephropathy

PLoS One. 2014 Jul 9;9(7):e101779. doi: 10.1371/journal.pone.0101779. eCollection 2014.

Abstract

Background: Endothelial injury, which may present clinically as hypertension, proteinuria and increased von Willebrand Factor (vWF) level, is a common manifestation in IgA nephropathy (IgAN). However, causal factors for endothelial injury in IgAN are not completely understood. An imbalance of vascular endothelial growth factor/Soluble fms-like tyrosine kinase-1 (VEGF/sFlt-1) has been observed in many diseases with endothelial dysfunction, including pre-eclampsia and diabetic retinopathy, but whether it contributes to endothelial injury in IgAN requires further exploration.

Methods: Initially, 96 IgAN patients and 22 healthy volunteers were enrolled as a discovery cohort. VEGF/sFlt-1, sFlt-1 and VEGF levels were compared between patients with IgAN and healthy volunteers to explore the underlying factors that contribute to endothelial injury in IgAN. The identified contributor (sFlt-1) was further confirmed in a replication cohort, which included 109 IgAN patients and 30 healthy volunteers. Correlations of sFlt-1 with hypertension, proteinuria, Oxford-E score and plasma vWF were further evaluated in the combined 205 patients with IgAN.

Results: VEGF/sFlt-1 levels were significantly lower in IgAN patients than healthy volunteers (0.33±0.27 vs. 0.43±0.22, p = 0.02) in the discovery cohort. Within the ratio, plasma sFlt-1 levels were significantly elevated (101.18±25.19 vs. 79.73±18.85 pg/ml, p<0.001), but plasma VEGF levels showed no significant differences. Elevated sFlt-1 levels in the replication cohort were confirmed in IgAN patients (93.40±39.78 vs. 71.92±15.78 pg/ml, p<0.001). Plasma sFlt-1 levels in IgAN patients correlated with proteinuria (severe (>3.5 g/d) vs. moderate (1-3.5 g/d) vs. mild (<1 g/d) proteinuria: 115.95±39.09 vs. 99.89±28.55 vs. 83.24±33.92 pg/ml; severe vs. mild: p<0.001, moderate vs. mild p = 0.001, severe vs. moderate: p = 0.014), hypertension (with vs. without hypertension: 107.87±31.94 vs. 87.32±32.76 pg/ml, p = 0.015) and vWF levels (r = 0.161, p = 0.021).

Conclusions: The present study found elevated sFlt-1 in IgAN patients and further identified its correlation with proteinuria, hypertension and vWF levels. These results suggested that elevated sFlt-1 contributes to endothelial injury in IgAN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Endothelium, Vascular / pathology
  • Female
  • Glomerulonephritis, IGA / blood*
  • Glomerulonephritis, IGA / physiopathology
  • Glomerulonephritis, IGA / urine
  • Humans
  • Hypertension / blood
  • Male
  • Proteinuria / blood
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-1 / blood*
  • Young Adult
  • von Willebrand Factor / metabolism

Substances

  • Biomarkers
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Von Willebrand antigen
  • von Willebrand Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1

Grant support

This work was supported by the National Natural Science Foundation for Innovative Research Groups of China (Grant No. 81021004) and by the National Natural Science Foundation for Youths of China (Grants No. 81000297 and 81200515). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.