title: Vascular endothelial growth factor C levels are modulated by dietary salt intake in proteinuric chronic kidney disease patients and in healthy subjects.
abstract: BACKGROUND
  Recent experimental findings demonstrate vascular endothelial growth factor C (VEGF-C)-mediated water-free storage of salt in the interstitium, which prevents a salt-sensitive blood pressure state. It is unknown whether this mechanism plays a role in salt homeostasis and regulation of blood pressure in humans as well. Therefore, we investigated circulating VEGF-C levels and blood pressure during different well-controlled salt intake in chronic kidney disease (CKD) patients and in healthy subjects.
  
  
  METHODS
  In two crossover studies, non-diabetic proteinuric CKD patients (n = 32) and healthy subjects (n = 31) were treated with consecutively a low-sodium diet (LS, aim 50 mmol Na(+)/day) and a high-sodium diet (HS, aim 200 mmol Na(+)/day) in random order, during two 6-week (CKD patients) and two 1-week periods (healthy subjects).
  
  
  RESULTS
  We found that VEGF-C levels are higher during HS than during LS in CKD patients (P = 0.034) with a trend towards higher VEGF-C in healthy subjects as well (P = 0.070). In CKD patients, HS was associated with higher NT-proBNP levels (P = 0.005) and body weight (P = 0.013), consistent with extracellular volume (ECV) expansion and with higher blood pressure (P < 0.001), indicating salt sensitivity. In healthy subjects, blood pressure was not affected by dietary salt (P = 0.14), despite a rise in ECV (P = 0.023).
  
  
  CONCLUSIONS
  Our findings support a role for VEGF-C-mediated salt homeostasis in humans. Considering the salt sensitivity of blood pressure, this buffering mechanism appears to be insufficient in proteinuric CKD patients. Future studies are needed to provide causality and to substantiate the clinical and therapeutic relevance of this VEGF-C regulatory mechanism in humans.
authors.affiliation: Department of Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Maartje C J
authors.initials: MC
authors.lastname: Slagman
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.forename: Saleh
authors.initials: S
authors.lastname: Yazdani
authors.forename: Gozewijn D
authors.initials: GD
authors.lastname: Laverman
authors.forename: Jaap
authors.initials: J
authors.lastname: van den Born
authors.forename: Jens
authors.initials: J
authors.lastname: Titze
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
mesh_terms: D000328:Adult; D001835:Body Weight; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004039:Diet, Sodium-Restricted; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D006973:Hypertension; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D042582:Vascular Endothelial Growth Factor C / Q000097:blood*; D055815:Young Adult
chemical_list: D017673:Sodium Chloride, Dietary; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C