Impaired endothelium‐dependent vasodilatation in renal failure in humans

Annuk, Margus; Lind, Lars; Linde, Torbjörn; Fellström, Bengt

doi:10.1093/ndt/16.2.302

Cited by 93 publications

(72 citation statements)

References 15 publications

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“…An association between endothelial dysfunction and renal impairment/failure has been demonstrated previously, but only in patients with more severe renal impairment (mean creatinine clearance, 30 mL/min) 36 and concomitant additional cardiovascular risk factors. We are unaware of any such relation within the clearance range reported in the present study.…”

Section: Booth Et Al Vasculitis and Endothelial Dysfunctionmentioning

confidence: 76%

Infliximab Improves Endothelial Dysfunction in Systemic Vasculitis

et al. 2004

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Background-Endothelial vasomotor dysfunction and markers of systemic inflammation are independent determinants of cardiovascular risk. However, the link between clinical inflammation and endothelial dysfunction is unclear. The aim of this study was to use anti-neutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) as a model of systemic inflammation in which to test the hypothesis that inflammation is associated with endothelial dysfunction and can be reversed with anti-tumor necrosis factor-␣ (TNF-␣) therapy. Methods and Results-Fourteen patients with active AASV and 21 age-matched control subjects were studied. Endothelial function was assessed through the use of forearm plethysmography and related to clinical disease activity: Birmingham Vasculitis Activity Score (BVAS) and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and TNF-␣. The effects of anti-TNF-␣ therapy (infliximab), either alone (nϭ6) or in combination with standard treatment (nϭ4), on endothelial function were subsequently determined. Patients had a mean BVAS of 11Ϯ1, and CRP and IL-6 were higher in the AASV group than in control subjects (34.8Ϯ10.5 versus 1.6Ϯ0.2 pg/mL, PϽ0.001; 9.0Ϯ0.7 versus 6.7Ϯ0.6 pg/mL, Pϭ0.02). Forearm blood flow response to acetylcholine (ACh) was reduced in the patients compared with control subjects (Pϭ0.002), but sodium nitroprusside (SNP) responses were not (Pϭ0.3). The response to ACh improved with infliximab treatment (Pϭ0.004) in particular, with infliximab alone (Pϭ0.03). Conclusions-AASV is associated with endothelial dysfunction. Anti-TNF-␣ therapy, alone or in combination with standard treatment, results in clinical remission, reduced inflammation, and improved endothelium-dependent vasomotor responses.

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Section: Booth Et Al Vasculitis and Endothelial Dysfunctionmentioning

confidence: 76%

Infliximab Improves Endothelial Dysfunction in Systemic Vasculitis

et al. 2004

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“…27 Furthermore, Thuraisingham et al could not demonstrate an impaired endothelium-dependent vasorelaxation in an experimental ex vivo animal study of advanced renal insufficiency, 28 whereas a large study on patients in the predialysis range reported attenuation in methacholineinduced vasodilatation. 29 Moreover, it is possible that this defect is selective for muscarinic receptor agonist as was found in a recent study on the age-dependent vasodilation capacity. 30 Thus, the issue to which extent renal impairment per se impairs endothelium-dependent vasodilatation remains to be further clarified.…”

Section: Discussionmentioning

confidence: 87%

Impaired Endothelial Release of Tissue-Type Plasminogen Activator in Patients With Chronic Kidney Disease and Hypertension

et al. 2004

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Abstract-We have shown that the capacity for local release of tissue-type plasminogen activator (tPA) from the vascular endothelium is impaired in patients with primary hypertension. Because this response is an important protective mechanism against intravascular clotting, we investigated whether this system is also defective in patients with advanced chronic kidney disease and hypertension. Nine nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration rate 11 to 28 mL/minϫ1.73 m 2 ; aged 33 to 75 years) were compared with age-matched healthy controls. Intraarterial infusions of desmopressin, methacholine, and sodium nitroprusside were given locally in the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography and blood collected repeatedly during the desmopressin infusion for determination of stimulated net and total cumulated release of tPA. The maximal release rate of active tPA (PϽ0.05) and the capacity for acute tPA release were markedly impaired in the renal patients as compared with healthy subjects (ANOVA, Pϭ0.013). Accordingly, the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue, respectively (PϽ0.05). However, there were no significant differences in vasodilator responses between the groups. Thus, patients with advanced chronic kidney disease and hypertension have a markedly impaired capacity for acute release of tissue plasminogen activator, despite preserved endothelium-dependent vasodilation. This defect may contribute to a defective local defense against arterial thrombosis.

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“…We suggest that the adaptive decrease in systemic vascular resistance may be impaired in chronic kidney disease as a result of endothelial dysfunction (40,41) and impairment of de novo angiogenesis (39,42). Endothelial dysfunction is a known consequence of renal insufficiency with impairment of vasodilation, which may interact with anemia to limit delivery of oxygen during hypoxia.…”

Section: Discussionmentioning

confidence: 94%

Association of High Serum Creatinine and Anemia Increases the Risk of Coronary Events

Jurkovitz

Abramson²,

Vaccarino³

et al. 2003

Journal of the American Society of Nephrology

173

108

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Abstract. Coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with chronic kidney disease or anemia. The purpose of this study was to examine whether the association between renal function and risk of CHD is modified by hemoglobin (Hgb) status. Analyses were based on data from the Atherosclerosis Risk in Communities study, a community-based study of risk factors for CHD in middle-aged people. People with known CHD at baseline were excluded from the analysis. Participants were followed for 9 yr for the occurrence of CHD. Anemia was defined as Hgb Ͻ13 g/dl in men and Ͻ12 g/dl in women. Cox proportional hazards models were used to assess the relative risk (RR) of CHD occurrence according to Hgb status, after adjusting for other risk factors (demographics, lipids, diabetes, hypertension, smoking, body mass index, and carotid intima-media thickness). A total of 13,329 participants were included. The interaction between Hgb concentration and serum creatinine (Scr) was significant (P ϭ 0.02). Among people with anemia, a Scr Ն1.2 mg/dl in women or Ն1.5 mg/dl in men was associated with a higher risk of CHD (RR, 2.74; 95% confidence interval, 1.42 to 5.28) than those with normal Scr. In contrast, among those without anemia, this association was not noted (RR, 1.20; 95% confidence interval, 0.86 to 1.67). In conclusion, this study indicates that high Scr is associated with almost a threefold risk of CHD among middle-aged people with anemia, whereas no increased risk is found in people with high Scr in the absence of anemia.Cardiovascular disease (CVD) mortality rates in ESRD are approximately 15 times higher than in the general population (1). Many studies examining the association between ESRD and cardiovascular mortality (2,3) have found that ESRD is an independent predictor of cardiovascular death. However, it is unclear whether moderate renal insufficiency is also associated with cardiovascular events. Previous studies conducted in patients at high risk of CVD have suggested that mild renal insufficiency may be an independent risk factor for cardiovascular events (4 -8). However, in analyses of population-based cohorts (9,10), there was no independent association between moderate renal insufficiency and cardiovascular mortality or nonfatal cardiovascular events after adjustment for traditional risk factors.Anemia is a frequent complication of chronic kidney disease (CKD) and is primarily due to failure of erythropoietin production to respond to decreased hemoglobin (Hgb) concentration (11,12). In chronic anemia, long-lasting flow/volume overload and increased cardiac work lead to progressive cardiac enlargement and left ventricular hypertrophy (13). The risk of coronary heart disease (CHD) increases when the anemia is not treated, and recent studies have indicated that anemia in patients with CKD may predispose to ischemic heart disease, heart failure, and premature death (14 -16). Therefore, the risk of CHD may be distinctly higher in people with renal insufficiency and concomitant ane...

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Impaired endothelium‐dependent vasodilatation in renal failure in humans

Abstract: Patients with moderate CRF have an impaired EDV even after correction for traditional cardiovascular risk factors and this impairment is related to the degree of renal failure.

Cited by 93 publications

References 15 publications

Infliximab Improves Endothelial Dysfunction in Systemic Vasculitis

Infliximab Improves Endothelial Dysfunction in Systemic Vasculitis

Impaired Endothelial Release of Tissue-Type Plasminogen Activator in Patients With Chronic Kidney Disease and Hypertension

Association of High Serum Creatinine and Anemia Increases the Risk of Coronary Events

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