title: Association between markers of collagen turnover, arterial stiffness and left ventricular hypertrophy in chronic kidney disease (CKD): the Renal Research Institute (RRI)-CKD study.
abstract: BACKGROUND
  Markers of collagen turnover have not been well studied in the context of cardiovascular disease in patients with chronic kidney disease (CKD). We investigated the associations between serum markers of collagen turnover [N-terminal procollagen type 3 propeptide (PIIINP) and carboxy-terminal telopeptide (C1TP)] and both pulse wave velocity (PWV) and left ventricular mass index (LVMI) in a CKD cohort.
  
  
  METHODS
  The study included 242 patients (mean age 60 ± 15 years, 53% males, 80% Caucasian, CKD Stages 3-5) from the Renal Research Institute (RRI)-CKD Study. Serum PIIINP and C1TP levels were analyzed by radioimmunoassay. PWV was obtained by applanation tonometry from carotid and femoral pressure wave contours. LVMI was measured by echocardiography. Statistical analyses included Pearson's correlations and multiple linear regression.
  
  
  RESULTS
  Both PIIINP and C1TP values were significantly higher in more advanced stages of CKD (P < 0.05). A positive correlation was demonstrated between PWV and LVMI (r = 0.25, P = 0.0018), persisting after adjustment for potential confounders (partial r = 0.27, P = 0.0009). PIIINP correlated with PWV (r = 0.16, p = 0.029) and LVMI (r = 0.16, P = 0.0018), while C1TP correlated with LVMI (r = 0.18, P = 0.013) but not with PWV (r = 0.12, P = 0.09). In multivariable analysis adjusting for race, diabetes, estimated glomerular filtration rate (eGFR) and renin-angiotensin-aldosterone system inhibitors, only PWV (β = 0.45, P = 0.0017) but not LVMI (P = 0.09) remained significantly associated with serum PIIINP.
  
  
  CONCLUSIONS
  Our results demonstrate the association of PIIINP (but not C1TP), a circulating biomarker of collagen synthesis with arterial stiffness (but not with LVMI) in a CKD cohort, independent of eGFR. This suggests that altered collagen turnover may play a role in the pathogenesis of arterial stiffness in CKD.
authors.affiliation: Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Santo
authors.initials: S
authors.lastname: Dellegrottaglie
authors.forename: Robin L
authors.initials: RL
authors.lastname: Sands
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Gillespie
authors.forename: Gowrishankar
authors.initials: G
authors.lastname: Gnanasekaran
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: David
authors.initials: D
authors.lastname: Sengstock
authors.forename: Frederic
authors.initials: F
authors.lastname: Finkelstein
authors.forename: Margaret
authors.initials: M
authors.lastname: Kiser
authors.forename: George
authors.initials: G
authors.lastname: Eisele
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hinderliter
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Levin
authors.forename: Valerie
authors.initials: V
authors.lastname: Cattan
authors.forename: Rajiv
authors.initials: R
authors.lastname: Saran
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
mesh_terms: D000047:Academies and Institutes; D001158:Arteries / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism*; D015331:Cohort Studies; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis* / Q000209:etiology* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D059289:Vascular Stiffness
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D003094:Collagen