Endotoxin and immune activation in chronic heart failure: a prospective cohort study

Niebauer, Josef; Volk, Hans‐Dieter; Kemp, Michael; Dominguez, Martin; Schumann, Ralf R.; Rauchhaus, Mathias; Poole‐Wilson, Philip A.; Coats, Andrew J.S.; Anker, Stefan D.

doi:10.1016/s0140-6736(98)09286-1

Cited by 778 publications

(556 citation statements)

References 25 publications

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“…When renal function declines, retention of advanced glycation end products and pro-oxidants, leading to oxidative damage, may contribute to the activation of mononuclear cells and stimulation of an inflammatory response [7,8] . Additional mechanisms by which a failing kidney function may promote inflammation include overhydration, a frequent complication in CKD patients that may contribute to inflammation via bacterial or endotoxin translocation associated with severe gut edema, resulting in immuno-activation and increased inflammatory cytokine production [9] . Additionally, comorbidities, often seen in connection with ESRD, such as congestive heart failure, diabetes mellitus, hypertension, and aging-related changes in the immune response may further enhance a chronic inflammatory state.…”

Section: Causes Of Inflammationmentioning

confidence: 99%

End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes

Dai

Gołembiewska

Lindholm

et al. 2017

Contributions to Nephrology

146

111

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Despite marked improvements in renal replacement therapy during the last 30 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients is still unacceptably high and comparable to that of many malignancies. Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in ESRD patients. However, traditional risk factors can only partially explain the high premature cardiovascular burden in this population. Nontraditional risk factors, including persistent low-grade inflammation, are critical in the pathogenesis of atherosclerosis, vascular calcification, and other causes of CVD and may also contribute to protein-energy wasting and other complications in chronic kidney disease (CKD) patients. Inflammatory biomarkers, such as high sensitivity C-reactive protein and interleukin-6, independently predict mortality in these patients. The causes of inflammation in CKD are multifactorial and include imbalance between increased production (due to multiple sources of inflammatory stimuli such as oxidative stress, acidosis, volume overload, co-morbidities, especially infections, genetic and epigenetic influences, and the dialysis procedure) and inadequate removal (due to decreased glomerular filtration rate or in ESRD patients, inadequate dialytic clearance) of pro-inflammatory cytokines. Though there are currently no established guidelines for the treatment of low-grade inflammation in ESRD patients, several strategies have been proposed, such as lifestyle modifications, pharmacological treatment, and optimization of dialysis. Further studies on pathways involved in pathogenic processes of inflammation in ESRD, and long-term effects of anti-inflammatory interventions targeting production or removal of cytokines or both on premature CVD and clinical outcomes in this patient group are warranted.

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Section: Causes Of Inflammationmentioning

confidence: 99%

End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes

Dai

Gołembiewska

Lindholm

et al. 2017

Contributions to Nephrology

146

111

View full text Add to dashboard Cite

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“…Many uremic toxins are known to be proinflammatory (35) and are inadequately removed with standard dialysis methods; alternative removal techniques, such as strategies to modify intestinal generation or absorption, may have a role in this regard (36). Appropriate management of fluid status might improve systemic inflammation in patients with ESRD because volume overload leads to immunoactivation and increased cytokine production via bacterial or endotoxin translocation (37).…”

Section: Prevention Of Pew: a Cause-specific Approachmentioning

confidence: 99%

A Patient with CKD and Poor Nutritional Status

İkizler

2013

Clinical Journal of the American Society of Nephrology

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SummaryProtein energy wasting is common in patients with CKD and ESRD and is associated with adverse clinical outcomes, such as increased rates of hospitalization and death, in these patients. A multitude of factors can affect the nutritional and metabolic status of patients with CKD, including decreased dietary nutrient intake, catabolic effects of renal replacement therapy, systemic inflammation, metabolic and hormonal derangements, and comorbid conditions (such as diabetes and depression). Unique aspects of CKD also confound reliable assessment of nutritional status, further complicating management of this comorbid condition. In patients in whom preventive measures and oral dietary intake from regular meals cannot help them maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is effective in replenishing protein and energy stores. The advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic steroids and exercise, with nutritional supplementation or alone, improve protein stores and represent potential additional approaches for the treatment of PEW. There are several emerging novel therapies, such as appetite stimulants, anti-inflammatory interventions, and anabolic agents.

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“…A study of clinically stable CHF patients has shown structurally and functionally altered gut, with increased bowel wall thickness suggestive of edema, and increased intestinal mucosal permeability suggestive of inadequate bowel mucosal perfusion (6). Endotoxin and cytokine levels are elevated in CHF patients with recent-onset edema compared with stable CHF patients, with a significant reduction in endotoxin levels following diuretic treatment (7). In decompensated CHF, endotoxin levels are significantly higher in the hepatic veins compared with the left ventricle, suggesting endotoxin translocation from the gut is the probable source (8).…”

Section: Introductionmentioning

confidence: 99%

The Impact of Antihypertensive Drug Therapy on Endotoxemia in Elderly Patients with Chronic Kidney Disease

John¹,

Owen²,

Harrison³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Endotoxin (ET) is recognized to cause adverse effects on cardiovascular (CV) structure. Circulatory translocation of gut bacterial ET is described in heart failure. Chronic kidney disease (CKD) is common in older people and aggressive BP control is the cornerstone of management. We therefore studied ET after improvement of the overall CV milieu with introduction of optimized antihypertensive therapy (AHT).Design, setting, participants, & measurements We recruited 40 hypertensive nondiabetic patients (Ն70 years) with CKD stages 3 and 4 and hypertensive non-CKD matched controls. Assessment was performed after complete AHT washout and repeated after AHT reintroduction to target BP 130/80 mmHg. Pulse wave velocity (PWV) and analysis were assessed by applanation tonometry, central hemodynamics by continuous digital pulse wave analysis, vascular calcification (VC) by superficial femoral artery CT, and serum ET by Limulus Amebocyte assay.Results Mean age was 76 Ϯ 5 years, estimated GFR (eGFR) (CKD group) was 40 Ϯ 14 ml/min per 1.73 m 2 , and achieved BP was 128/69 mmHg. Washout ET was 0.042 Ϯ 0.011 EU/ml and was independent of renal function, gender, age, BP, VC, arterial stiffness, and high-sensitivity C-reactive protein. ET significantly decreased with AHT (to 0.020 Ϯ 0.028 EU/ml; P Ͻ 0.001) and was associated with eGFR (R ϭ Ϫ0.38; P ϭ 0.02), arterial wave reflection (Augmentation Index R ϭ Ϫ0.42; P ϭ 0.01), and degree of tonic vasodilatation (total peripheral resistance R ϭ Ϫ0.37; P ϭ 0.03), but not VC, PWV, gender, age, BP, or high-sensitivity C-reactive protein.Conclusions Elderly patients with hypertension have elevated serum ET. Improvement of their CV status with optimized AHT is associated with a significant reduction in endotoxemia. Further investigation of the potential pathophysiological mechanisms linking CV disease and CKD with this previously unappreciated effect of AHT appears warranted.

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Endotoxin and immune activation in chronic heart failure: a prospective cohort study

Cited by 778 publications

References 25 publications

End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes

End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes

A Patient with CKD and Poor Nutritional Status

The Impact of Antihypertensive Drug Therapy on Endotoxemia in Elderly Patients with Chronic Kidney Disease

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