Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study

Landray, Martin J; Wheeler, David C.; Lip, Gregory Y.H.; Newman, David J.; Blann, Andrew D.; McGlynn, Fiona J; Ball, Simon; Townend, Jonathan N.; Baigent, Colin

doi:10.1053/j.ajkd.2003.10.037

Cited by 279 publications

(207 citation statements)

References 42 publications

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“…Atherosclerosis is today considered to be, in part, an inflammatory disease [27]. Impaired renal function is also associated with increased inflammatory activity [28,29] and other factors that are considered to be important for the development of CVD, such as endothelial dysfunction, increased endothelin production [29,30] and increased sympathetic nerve activity [30]. Thus, there are many similarities between CVD and CKD patients, and the pathogenesis of renal impairment and atherosclerotic vascular disease may share several common features.…”

Section: Discussionmentioning

confidence: 99%

Prognostic implications of renal dysfunction in patients with stable angina pectoris

Almquist

Forslund

Rehnqvist

et al. 2006

Journal of Internal Medicine

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Objective. Impaired renal function is emerging as an independent risk factor for cardiovascular (CV) disease. We analysed the prognostic implications of estimated renal function in patients with angina pectoris. Design. Post hoc analysis of the Angina Prognosis Study In Stockholm (APSIS). The estimated creatinine clearance (eCrCl) was calculated according to the Cockcroft-Gault formula in 808 patients. Outcomes were compared for subgroups with CrCl ‡90, 60-89 and<60 mL min )1 . Setting. Hospital-based study with patients referred from primary care and hospital. Subjects. A total of 809 patients (248 women) with clinically diagnosed stable angina pectoris. Intervention. Double-blind treatment with metoprolol or verapamil.Results. One hundred and sixty-four patients (91 women) had an eCrCl below 60 mL min )1 . During a median follow-up of 40 months, 38 patients suffered CV death and 31 patients had a nonfatal myocardial infarction (MI). In a univariate analysis a lower eCrCl was related to a higher risk for CV death or MI amongst men (log rank P ¼ 0.036). A multivariate Cox analysis showed an independent prognostic importance of eCrCl for CV death (P ¼ 0.046) and for CV death or MI (P ¼ 0.042) amongst all patients. When analysed as a continuous variable, a 1 mL min )1 decrease in eCrCl was associated with a 1.6% (0.1-3.1) increase in the risk for CV death or MI, and a 2.1% (0-4.1) increase in the risk for CV death alone. Conclusion. Renal dysfunction was found to be common in patients with stable angina pectoris and estimated creatinine clearances carried significant independent prognostic information regarding CV death and nonfatal MI.

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Section: Discussionmentioning

confidence: 99%

Prognostic implications of renal dysfunction in patients with stable angina pectoris

Almquist

Forslund

Rehnqvist

et al. 2006

Journal of Internal Medicine

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“…The increased risk of CVD in this patient population is only partially explained by traditional (Framingham)5, 6 risk factors, and “nontraditional” factors likely influence the risk of CVD 7. Systemic inflammation has been proposed to contribute to the development of CVD in patients with CKD,8 as inflammatory markers, such as C‐reactive protein and interleukin‐6, are elevated in CKD 9, 10, 11, 12. In some observational studies, cytokines prospectively predicted the development of CVD 12…”

Section: Introductionmentioning

confidence: 99%

Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease

Jalal

Renner

Laskowski

et al. 2018

JAHA

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BackgroundEndothelial microparticles are associated with chronic kidney disease (CKD) and complement activation. We hypothesized that the complement pathway is activated in patients with CKD via endothelial microparticles and that complement activation correlates with endothelial dysfunction in CKD.Methods and ResultsWe analyzed complement data of 30 healthy subjects, 30 patients with stage III/IV CKD, and 30 renal transplant recipients with stage III/IV CKD, evaluating the potential correlation of complement fragments with brachial artery flow–mediated dilation, Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and urinary albumin/creatinine ratio. Endothelial microparticles were characterized via proteomic analysis and compared between study groups. Complement fragment Ba was significantly increased in CKD and post–kidney transplant CKD. Plasma Ba levels correlated significantly with lower brachial artery flow–mediated dilation, lower Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and higher urinary albumin/creatinine ratio. Factor D levels were significantly higher in the plasma microparticles of patients with CKD versus healthy controls. Plasma microparticles isolated from patients with CKD and containing factor D activated the alternative pathway in vitro.ConclusionThe alternative complement pathway is activated in CKD and correlates with endothelial dysfunction and markers of CKD. Future studies are needed to evaluate whether endothelial microparticles with increased factor D play a pathologic role in CKD‐associated vascular disease.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02230202.

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“…14,[16][17][18][19] The impact of CKD on plasma ADMA levels is not yet clear. In a small series (n = 11) we found that plasma ADMA levels are variable in CKD patients and are not correlated with severity of CKD.…”

Section: Adma In Chronic Kidney Diseasementioning

confidence: 99%

“…Indeed, endothelial dysfunction does occur in CKD (characterized by blunted release of endothelial NO) and in ESRD, even during early stages of disease. [14][15][16][17][18] Although no clinical evidence is available, animal studies implicate intrarenal NO deficiency in CKD, and this is another factor that would contribute to falls in the UNO X V index. [7][8][9][10][11][12][13] Given the persistent oxidative stress induced in early-stage CKD, 19 reduced NO synthesis is likely to be widespread in both CKD and ESRD (see below).…”

Section: Introductionmentioning

confidence: 99%

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

2006

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SummaryNitric oxide (NO) production is reduced in renal disease, partially due to decreased endothelial NO production. Evidence indicates that NO deficiency contributes to cardiovascular events and progression of kidney damage. Two possible causes of NO deficiency are substrate (L-arginine) limitation and increased levels of circulating endogenous inhibitors of NO synthase (particularly asymmetric dimethylarginine [ADMA]). Decreased L-arginine availability in chronic kidney disease (CKD) is due to perturbed renal biosynthesis of this amino acid. In addition, inhibition of transport of L-arginine into endothelial cells and shunting of L-arginine into other metabolic pathways (e.g. those involving arginase) might also decrease availability. Elevated plasma and tissue levels of ADMA in CKD are functions of both reduced renal excretion and reduced catabolism by dimethylarginine dimethylaminohydrolase (DDAH). The latter might be associated with loss-offunction polymorphisms of a DDAH gene, functional inhibition of the enzyme by oxidative stress in CKD and end-stage renal disease, or both. These findings provide the rationale for novel therapies, including supplementation of dietary L-arginine or its precursor L-citrulline, inhibition of non-NOproducing pathways of L-arginine utilization, or both. Because an increase in ADMA has emerged as a major independent risk factor in end-stage renal disease (and probably also in CKD), lowering ADMA concentration is a major therapeutic goal; interventions that enhance the activity of the ADMA-hydrolyzing enzyme DDAH are under investigation.

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Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study

Cited by 279 publications

References 42 publications

Prognostic implications of renal dysfunction in patients with stable angina pectoris

Prognostic implications of renal dysfunction in patients with stable angina pectoris

Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

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