Serum Levels of Soluble Adhesion Molecules in Chronic Renal Failure and Dialysis Patients

Bonomini, Mario; Reale, Marcella; Santarelli, Patrizia; Stuard, Stefano; Settefrati, N.; Albertazzi, A

doi:10.1159/000045084

Cited by 114 publications

(109 citation statements)

References 31 publications

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“…Although little is known about the route of elimination of these molecules, an important role of the kidney has been suggested, since levels of sVCAM-1 were strongly associated with serum creatinine levels among subjects with chronic renal failure not receiving dialysis (45,46). Nevertheless, we found sVCAM-1 levels to be associated with risk of cardiovascular mortality independent of estimates of glomerular filtration rate.…”

Section: Discussionmentioning

confidence: 50%

Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study.

et al. 2000

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Membrane-bound vascular cell adhesion molecule 1 (VCAM-1) allows the tethering and rolling of monocytes and lymphocytes as well as firm attachment and transendothelial migration of leukocytes. Soluble forms of VCAM (sVCAM-1) may serve as monitors of increased expression of membrane-bound VCAM-1 and thus may reflect progressive formation of atherosclerotic lesions. Levels of sVCAM-1 have been found to be increased among type 2 diabetic as compared with nondiabetic subjects. To study the association of plasma sVCAM-1 concentration and risk of cardiovascular and all-cause mortality among nondiabetic and diabetic subjects, we investigated an age-, sex-, and glucose-tolerance-stratified sample (n = 631) of a populationbased cohort aged 50-75 years that was followed p r o s p e c t i v e l y. Plasma levels of sVCAM-1 were determined in frozen -70°C baseline samples. After 7.4 years (mean) of follow-up, 107 (17%) subjects had died ( 4 2 of cardiovascular causes). In the entire group, increased sVCAM-1 levels were significantly associated with increased risk of cardiovascular mortality (relative risks [RRs] per 100 ng/ml sVCAM-1 increase, 1.10 [1.05-1.15] after adjustment for age, sex, and glucose tolerance status). This RR was somewhat diminished by further adjustment for the presence of hypertension and cardiovascular disease; levels of total, HDL, and LDL cholesterol and homocysteine; the presence of microalbuminuria (a putative marker of endothelial dysfunction); levels of von Willebrand factor (a marker of endothelial dysfunction) and C-reactive protein (a marker of low-grade inflammation); and estimates of glomerular filtration rate. However, the RR remained statistically significant. The RR among type 2 diabetic subjects was 1.13 (1.07-1.20) per 100 ng/ml sVCAM-1 increase after adjustment for age and sex, which was somewhat higher but not significantly different from the RR in nondiabetic subjects (P value for interaction term, 0.12). Further adjustment for other risk factors gave similar results. In conclusion, levels of sVCAM-1 are independently associated with the risk of cardiovascular mortality in type 2 diabetic subjects and therefore might be useful for identifying subjects at increased cardiovascular risk. Increased plasma sVCAM-1 levels may reflect progressive formation of atherosclerotic lesions, or sVCAM-1 itself may have bioactive properties related to cardiovascular risk. Our data, however, argue against the hypotheses of sVCAM-1 levels simply being a marker of endothelial dysfunction, of low-grade inflammation, or of an impaired renal function. D i a b e t e s 4 9 :4 8 5-491, 2000

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Section: Discussionmentioning

confidence: 50%

Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study.

et al. 2000

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“…Serum E-selectin, a surrogate marker of endothelial activation, is also increased in dialysis patients. 49,50 Increased synthesis/release after cytokine stimulation 51 and inadequate clearance because of renal failure can both be responsible for the high levels. We found similar increased levels of sEselectin in our dialysis group but no relationship with the changes in imaging parameters or serum levels of glycocalyx constituents.…”

Section: Discussionmentioning

confidence: 99%

Damage of the Endothelial Glycocalyx in Dialysis Patients

Vlahu¹,

Lemkes²,

Struijk

et al. 2012

Journal of the American Society of Nephrology

233

229

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Damage to the endothelial glycocalyx, which helps maintain vascular homeostasis, heightens the sensitivity of the vasculature to atherogenic stimuli. Patients with renal failure have endothelial dysfunction and increased risk for cardiovascular morbidity and mortality, but the state of the endothelial glycocalyx in these patients is unknown. Here, we used Sidestream Darkfield imaging to detect changes in glycocalyx dimension in dialysis patients and healthy controls from in vivo recordings of the sublingual microcirculation. Dialysis patients had increased perfused boundary region and perfused diameters, consistent with deeper penetration of erythrocytes into glycocalyx, indicating a loss of glycocalyx barrier properties. These patients also had higher serum levels of the glycocalyx constituents hyaluronan and syndecan-1 and increased hyaluronidase activity, suggesting the shedding of these components. Loss of residual renal function had no influence on the imaging parameters but did associate with greater shedding of hyaluronan in blood. Furthermore, patients with higher levels of inflammation had more significant damage to the glycocalyx barrier. In conclusion, these data suggest that dialysis patients have an impaired glycocalyx barrier and shed its constituents into blood, likely contributing to the sustained endothelial cell activation observed in ESRD.

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“…[46,62,63] The observed inflammatory response in CRF rats in the current study was found to be associated with an enhanced hyper-adhesive state demonstrated by increased levels of plasma sICAM-1. This increase may be due to inadequate clearance and enhanced synthesis/release, [63,64] and it reflects the presence of CRF complications as malnutrition, inflammation, and cardiovascular diseases. [63,64] A significant correlation between sICAM-1 and other inflammatory cytokines as TNF-a and C-reactive protein was reported, [65,66] suggesting that the circulating level of this molecule may be regarded as a marker of inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

“…This increase may be due to inadequate clearance and enhanced synthesis/release, [63,64] and it reflects the presence of CRF complications as malnutrition, inflammation, and cardiovascular diseases. [63,64] A significant correlation between sICAM-1 and other inflammatory cytokines as TNF-a and C-reactive protein was reported, [65,66] suggesting that the circulating level of this molecule may be regarded as a marker of inflammatory process. When malnutrition of uremia ensured, decreased plasma amino acids, including L-arginine, [67] could enhance this inflammatory state.…”

Section: Discussionmentioning

confidence: 99%

Multiple Antioxidants and L-Arginine Modulate Inflammation and Dyslipidemia in Chronic Renal Failure Rats

Korish

2010

Renal Failure

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The kidney is an important source of L-arginine, the endogenous precursor of nitric oxide (NO). Surgical problems requiring extensive renal mass reduction (RMR) decrease renal NO production, leading to multiple hemodynamic and homeostatic disorders manifested by hypertension, oxidative stress, and increased inflammatory cytokines. Using the RMR model of chronic renal failure (CRF), we assessed the effects of twelve weeks' administration of L-arginine and/or a mixture of antioxidants (L-carnitine, catechin, vitamins E and C) on plasma cytokines, soluble intercellular adhesion molecule-1 (sICAM-1), nitrate and nitrites (NO 2 /NO 3 ), lipid profile, blood pressure, and renal function. CRF rats showed increased plasma IL-1a, IL1-b, IL-6, TNF-a, and sICAM-1 levels and decreased anti-inflammatory cytokines IL-4 and 10 levels, hypertension, and dyslipidemia. L-arginine treatment improved kidney functions, decreased systolic blood pressure, and decreased inflammatory cytokines levels. Antioxidants administration decreased inflammatory cytokines and sICAM-1 levels and increased IL-4 levels. Combined use of both L-arginine and the antioxidant mixture were very effective in their tendency to recover normal values of kidney functions, plasma cytokines, sICAM-1, blood pressure, NO 2 /NO 3 , cholesterol, and triglycerides concentrations. Indeed, the effects of L-arginine and the antioxidants on the reduction of proinflammatory cytokines may open new perspectives in the treatment of uremia.

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Serum Levels of Soluble Adhesion Molecules in Chronic Renal Failure and Dialysis Patients

Cited by 114 publications

References 31 publications

Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study.

Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study.

Damage of the Endothelial Glycocalyx in Dialysis Patients

Multiple Antioxidants and L-Arginine Modulate Inflammation and Dyslipidemia in Chronic Renal Failure Rats

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