title: Effect of GFR on plasma N-terminal connective tissue growth factor (CTGF) concentrations.
abstract: BACKGROUND
  Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-CTGF is a uremic retention solute that accumulates in chronic kidney disease (CKD) due to decreased renal clearance and whether it can be removed by hemodiafiltration.
  
  
  METHODS
  4 observational studies in patients and 2 pharmacokinetic studies in rodents.
  
  
  METHODS
  4 single-center studies. First study (cross-sectional): 88 patients with CKD not receiving kidney replacement therapy. Second study (cross-sectional): 23 patients with end-stage kidney disease undergoing low-flux hemodialysis. Third study: 9 kidney transplant recipients before and 6 months after transplant. Fourth study: 11 low-flux hemodialysis patients and 12 hemodiafiltration patients before and after one dialysis session.
  
  
  METHODS
  First, second, and third study: (residual) glomerular filtration rate (GFR). Fourth study: dialysis modality.
  
  
  METHODS
  Plasma (N-)CTGF concentrations, measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  In patients with CKD, we observed an independent association between plasma CTGF level and estimated GFR (β = -0.72; P < 0.001). In patients with end-stage kidney disease, plasma CTGF level correlated independently with residual kidney function (β = -0.55; P = 0.046). Successful kidney transplant resulted in a decrease in plasma CTGF level (P = 0.008) proportional to the increase in estimated GFR. Plasma CTGF was not removed by low-flux hemodialysis, whereas it was decreased by 68% by a single hemodiafiltration session (P < 0.001). Pharmacokinetic studies in nonuremic rodents confirmed that renal clearance is the major elimination route of N-CTGF.
  
  
  CONCLUSIONS
  Observational studies with limited number of patients. Fourth study: nonrandomized, evaluation of the effect of one session; randomized longitudinal study is warranted.
  
  
  CONCLUSIONS
  Plasma (N-)CTGF is eliminated predominantly by the kidney, accumulates in CKD, and is decreased substantially by a single hemodiafiltration session.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. k.g.f.gerritsen@umcutrecht.nl
authors.forename: Karin G
authors.initials: KG
authors.lastname: Gerritsen
authors.forename: Alferso C
authors.initials: AC
authors.lastname: Abrahams
authors.forename: Hilde P
authors.initials: HP
authors.lastname: Peters
authors.forename: Tri Q
authors.initials: TQ
authors.lastname: Nguyen
authors.forename: Maarten P
authors.initials: MP
authors.lastname: Koeners
authors.forename: Claire H
authors.initials: CH
authors.lastname: den Hoedt
authors.forename: Amelie
authors.initials: A
authors.lastname: Dendooven
authors.forename: Marinus A
authors.initials: MA
authors.lastname: van den Dorpel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Blankestijn
authors.forename: Jack F
authors.initials: JF
authors.lastname: Wetzels
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
authors.forename: Roel
authors.initials: R
authors.lastname: Goldschmeding
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Kok
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002908:Chronic Disease; D055513:Connective Tissue Growth Factor / Q000097:blood* / Q000493:pharmacokinetics; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D017583:Hemodiafiltration; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D023421:Models, Animal; D051381:Rats; D011921:Rats, Inbred WKY; D006435:Renal Dialysis
chemical_list: D055513:Connective Tissue Growth Factor