title: Elevated soluble VEGF receptor sFlt-1 correlates with endothelial injury in IgA nephropathy.
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.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Zhai
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Shi
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Liu
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Lv
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000503:physiopathology / Q000652:urine; D006801:Humans; D006973:Hypertension / Q000097:blood; D008297:Male; D011507:Proteinuria / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1