Impaired renal function is associated with markers of endothelial dysfunction and increased inflammatory activity.
BACKGROUND
Patients with end-stage renal disease (ESRD) as well as those with mild renal insufficiency are at increased risk for the development of cardiovascular disease, which cannot be attributed entirely to traditional risk factors. Endothelial dysfunction and chronic inflammatory activity, two important phenomena in atherogenesis, can be found in ESRD. At present, it is unclear whether endothelial dysfunction and chronic inflammatory activity are related to renal function in the pre-dialysis stage.


METHODS
In a cross-sectional, single-centre study, four groups of 20 subjects with renal function ranging from a normal, calculated creatinine clearance (>90 ml/min) to a pre-dialysis situation (<31 ml/min) were investigated. We measured markers of endothelial function [von Willebrand factor (vWf), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and E-selectin (ES)], and markers of inflammatory activity [secretory phospholipase A(2) (sPLA(2)) and C-reactive protein (CRP)]. Using these markers, composite endothelial function and inflammatory activity scores were constructed.


RESULTS
Creatinine clearance correlated with the endothelial function score (r=-0.43, P<0.001), the inflammatory activity score (r=-0.53, P<0.05), vWf (r=-0.54, P<0.001), sVCAM-1 (r=-0.50, P<0.001), sPLA(2) (r=-0.28, P<0.05), homocysteine (r=-0.61, P<0.001), age (r=-0.54, P<0.001) and blood pressure (r=-0.44, P<0.001). In multivariate analyses, creatinine clearance was an independent determinant of the endothelial function score (beta=-0.34, P=0.006), plasma vWf (beta=-0.37, P=0.022) and sICAM-1 (beta=-0.33, P=0.012). The relationship of creatinine clearance with sVCAM-1 and endothelial function score was not significant when plasma homocysteine was added to the model. Creatinine clearance was also a determinant of the inflammatory activity score (beta=-0.31, P=0.025) and sPLA(2) (beta=-0.32, P=0.024), although this was no longer significant after correction for systolic blood pressure.


CONCLUSIONS
Renal dysfunction is associated with markers of endothelial dysfunction and inflammatory activity. Plasma homocysteine may be an intermediate factor in the relationship between endothelial dysfunction and renal function, while blood pressure may modulate the association between inflammatory activity and renal function.
Stam
Frank
F
Department of Internal Medicine, Institute for Cardiovascular Research, Vrije Universiteit Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. f.stam@vumc.nl
van Guldener
Coen
C
Schalkwijk
Casper G
CG
ter Wee
Piet M
PM
Donker
Ab J M
AJ
Stehouwer
Coen D A
CD
D015415:Biomarkers / Q000032:analysis; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D012307:Risk Factors
D015415:Biomarkers; D018836:Inflammation Mediators; D006710:Homocysteine; D003404:Creatinine