Endothelin-1 Plasma Levels in Hemodialysis Treatment—The Influence of Type 2 Diabetes

Abstract

In patients on chronic hemodialysis the prevalence of atherosclerosis is increased and is by far the leading cause of morbidity and mortality. Endothelin-1, an endothelium-derived peptide with vasoconstrictive and mitogenic effects on vascular smooth muscles, is involved in the pathogenesis of atherosclerosis. The aim of the present study was to investigate the time course of plasma endothelin-1 levels during a hemodialysis session and to explore the influence of preexisting type 2 diabetes mellitus. Forty-five clinically stable hemodialysis patients (21 females, 24 males; mean age 62 +/- 12 years) were evaluated. Patients with type 2 diabetes (n= 11) were compared with the group of patients without diabetes (n=34). Relative blood volume (BV) changes (hemoglobinometry) and blood pressure (BP) was measured. Samples were taken before, every hour during, and after hemodialysis. Plasma endothelin-1 levels were measured by enzyme-linked immunoassay (ELISA) and results were corrected according to hemoconcentration. Hemodialysis with an ultrafiltration of 2215 +/- 952 mL was performed. Total BV at the end of hemodialysis was 89.3% +/- 8.3% of the pretreatment volume. Plasma endothelin-1 was enhanced in hemodialysis patients compared to normal subjects and increased from 1.28 +/- 0.47 before to 1.44 +/- 0.54 pg/mL (ref. 0.3-0.9) at the end of hemodialysis (p<0.05). The BV change (r=0.41) and the BP (mean BP: r=0.34) correlated with plasma endothelin-1 at the end of hemodialysis (p<0.05). The levels of endothelin-1 were significantly higher in the group of dialysis patients with type 2 diabetes compared to nondiabetics in all measurements (p<0.05). These findings suggest a potential role of endothelin-1 in the pathogenesis of vascular dysfunction in diabetes mellitus. The dialysis procedure per se, through vasoconstriction due to BV decrease, local endothelial injury (a.v. fistula), or bioincompatibility reactions (foreign surface contact) may additionally alter endothelial cell functions.

Effect of Dialysate Temperature and Diabetes on Autonomic Cardiovascular Regulation during Hemodialysis

“…Decreased concentrations of nitric oxide end products and increased endothelin-1 levels were found at the end of hemodialysis [30] . Significantly higher endothelin-1 levels were shown in hemodynamically stable diabetic patients when compared to stable non-diabetic patients [31] .…”

Increased Levels of Soluble TNF-α Receptors and Cellular Adhesion Molecules in Patients Undergoing Bioincompatible Hemodialysis

“…The studies on effects of different types of dialyzer systems provided even further evidence that increased sVCAM-1 are rather associated with immunological response to HD, whereas sICAM-1 and E-selectin increased rather due to uremia than the characteristics of HD membrane [16]. The levels of adhesion molecules sICAM-1 and sVCAM-1 do not appear to be affected by the HD both with low-flux cuprophane and high-flux polysulfone dialyzers [24]. Moreover, the levels of sICAM-1 and sVCAM-1 were not affected by coexisting diabetes mellitus, hypertension, or biocompatible, high-flux membranes [24].…”

“…The levels of adhesion molecules sICAM-1 and sVCAM-1 do not appear to be affected by the HD both with low-flux cuprophane and high-flux polysulfone dialyzers [24]. Moreover, the levels of sICAM-1 and sVCAM-1 were not affected by coexisting diabetes mellitus, hypertension, or biocompatible, high-flux membranes [24]. However, the increased CRP levels in HD patients most likely correspond with the use of low-flux, relatively bioincompatible cuprophane dialyzer in our patient study group.…”

Plasma endothelin-1 level, measured glomerular filtration rate and effective renal plasma flow in diabetic nephropathy

“…It is known that patients with advanced chronic kidney disease or on dialysis have higher plasma concentrations of ET-1. [17][18][19][20] A small number of clinical studies have examined the relationship of plasma ET-1 to GFR across different stages of renal impairment. Therefore, the aim of this study was to evaluate the correlation between serum concentrations of ET-1 and renal functional parameters (glomerular filtration rate and effective renal plasma flow) in patients with diabetic nephropathy.…”