Extracellular overhydration linked with endothelial dysfunction in the context of inflammation in haemodialysis dependent chronic kidney disease

Mitsides, Nicos; Cornelis, T.; Broers, Natascha J. H.; Diederen, Nanda M. P.; Brenchley, Paul; Sande, Frank M. van der; Schalkwijk, Casper G.; Kooman, Jeroen P.; Mitra, Sandip

doi:10.1371/journal.pone.0183281

Cited by 55 publications

(57 citation statements)

References 62 publications

(71 reference statements)

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“…Although fluid loading may lead to ESL shedding by atrial natriuretic peptide [28], there is as yet no direct evidence for a relation between ESL damage and fluid overload (FO) in dialysis patients. However, we recently observed higher levels of the vascular cell adhesion molecule 1 in FO as compared to normovolemic dialysis patients, suggesting a relation between endothelial dysfunction and FO [31]. Also, in chronic kidney disease non-dialysis patients, angiopoietin 2, a factor that stimulates capillary permeability, was significantly related to FO [32].…”

Section: Abnormalities In Fluid Volume Distributionmentioning

confidence: 83%

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Body Fluids in End-Stage Renal Disease: Statics and Dynamics

Kooman

Sande²

2018

Blood Purif

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Background: Abnormalities in fluid status in hemodialysis (HD) patients are highly prevalent and are related to adverse outcomes. Summary: The inherent discontinuity of the HD procedure in combination with an often compromised cardiovascular response is a major contributor to this phenomenon. In addition, systemic inflammation and endothelial dysfunction are related to extracellular fluid overload (FO). Underlying this relation may be factors such as hypoalbuminemia and an increased capillary permeability, leading to an altered fluid distribution between the blood volume (BV) and the interstitial fluid compartments, compromising fluid removal during dialysis. Indeed, whereas estimates of extracellular volume by bioimpedance spectroscopy are highly predictive of mortality, absolute BV assessed by the saline dilution technique was predictive of intra-dialytic morbidity. Changes in relative BV during HD are positively related to ultrafiltration rate (UFR) and, at least in some studies, negatively to FO. High UFR is also related to changes in central venous oxygen saturation (S_cvO₂), a marker for tissue perfusion. On the one hand, high UFR and more pronounced declines in S_cvO₂, but on the other hand, flat relative BV curves are also predictive of mortality; the relation between outcome which statics and dynamics of fluid status appears to be complex. Key Message: While technological developments enable the clinician to monitor statics and dynamics of fluid status and hemodynamics during HD in an accessible way, the role of technology-based interventions needs further study.

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Section: Abnormalities In Fluid Volume Distributionmentioning

confidence: 83%

“…Various studies have shown a relation between FO and inflammation [2,31,33]. The relation between FO and inflammation is likely complex and has been discussed in detail in a recent review paper [34].…”

Section: Non-cardiovascular Factors On Abnormalities In Fluid Statusmentioning

confidence: 99%

Body Fluids in End-Stage Renal Disease: Statics and Dynamics

Kooman

Sande²

2018

Blood Purif

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“…The 90th percentile of ∆HS in a normal reference population has been reported to be -7% to 7% [24]. Accordingly, a ∆HS ≥7% is considered to represent fluid overload, as previously validated in 350 Taiwanese healthy controls and 338 patients with chronic kidney disease [24], as well as in maintenance HD [25] and peritoneal dialysis patients [23]. Therefore, in the present study ∆HS was used to represent the severity of fluid status, with ∆HS ≥7% being defined as fluid overload.…”

Section: Measurement Of Fluid Statusmentioning

confidence: 84%

“…The OH was calculated as absolute changes in tissue hydration using a model including normally hydrated lean tissue and adipose tissue, as well as excess fluid mass, which was taken to represent OH [22]. Increasing evidence has shown that the relative hydration status (∆HS; ∆HS = OH/ECW) can be used as an indicator of fluid status [23][24][25]. The 90th percentile of ∆HS in a normal reference population has been reported to be -7% to 7% [24].…”

Section: Measurement Of Fluid Statusmentioning

confidence: 99%

Independent Association of Overhydration with All-Cause and Cardiovascular Mortality Adjusted for Global Left Ventricular Longitudinal Systolic Strain and E/E’ Ratio in Maintenance Hemodialysis Patients

Huang

Tsai

et al. 2018

Kidney Blood Press Res

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Background/Aims: Fluid overload is common and associated with morbidity and mortality in patients with end-stage renal disease. The relationship between fluid overload and cardiac function is complex, and whether fluid overload is associated with adverse outcomes in patients undergoing hemodialysis (HD) independently of systolic and diastolic function of the left ventricle (LV) remains unclear. Methods: The present study aimed to investigate the relationship between overhydration and all-cause and cardiovascular (CV) mortality after adjusting for LV function in 178 maintenance HD patients. The relative hydration status (overhydration/ extracellular water, ∆HS) was measured using a body composition monitor, and then used to assess the fluid status. A ∆HS ≥7% was defined as fluid overload. Global left ventricular longitudinal systolic strain (GLS), and the early filling and early diastolic mitral annular velocity (E/E’) ratio were assessed using speckle-tracking and tissue Doppler echocardiography. Results: During a mean follow-up period of 2.7 years, 24 patients died, including 11 CV deaths. An increased ∆HS was significantly associated with all-cause and CV mortality in the univariate analysis. This prognostic significance remains after multivariate adjusting for GLS and E/E’ ratio for all-cause (HR, 1.123; 95% CI, 1.063–1.186; p-value < 0.001) and CV (HR, 1.088; 95% CI, 1.005–1.178; p-value =0.037) mortality. Moreover, ∆HS significantly improved the prognostic value beyond conventional clinical and echocardiographic parameters. Conclusion: A higher ∆HS was independently associated with increased all-cause and CV mortality after adjusting for systolic and diastolic function of the LV. This suggests that ∆HS may be a relevant target for improving outcomes in maintenance HD patients.

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“…In addition to mechanical stimuli, ECF excess can contribute to vascular calcification through inflammation and oxidation. Several experimental and clinical studies have reported that inflammatory biomarkers such as tumor necrosis factor‐α, IL‐6, vascular adhesion molecule‐1, macrophage, and thrombomodulin were systemically or locally increased in the presence of ECF excess 39, 40. ECF excess directly induces a phenotype change in VSCMs and indirectly induces oxidative stress, which increases the production of bone morphogenetic protein 2 and endothelial cell–derived microparticles in endothelial cells, thereby enhancing the osteogenic signal acting on VSMCs 41, 42, 43…”

Section: Discussionmentioning

confidence: 99%

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease

Park

Jhee

Yun

et al. 2018

JAHA

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BackgroundExtracellular fluid (ECF) excess is an independent predictor of cardiovascular morbidity in patients undergoing dialysis. This study aimed to investigate the relationship between ECF status, which is affected by renal function, and coronary artery calcification (CAC), which is a marker of cardiovascular disease, in patients with chronic kidney disease (CKD).Methods and ResultsA total of 1741 patients at all stages of pre‐dialysis CKD from the prospective observational cohort of CMERC‐HI (Cardiovascular and Metabolic Disease Etiology Research Center‐High Risk) were analyzed for the association between ECF status and CAC. ECF status was defined as extracellular water‐to‐total body water ratio (ECW/TBW) measured using bioelectrical impedance analysis. ECF excess was defined as ECW/TBW ≥0.390 or ≥0.400 depending on its severity. To define CAC, Agatston coronary artery calcium scores were measured. A total coronary artery calcium score of ≥400 was defined as CAC. The CKD stages were defined according to estimated glomerular filtration rate calculated using the CKD Epidemiology Collaboration equation. ECW/TBW and the proportion of ECF excess increased with progressing CKD stages. Multivariable logistic regression analyses showed that ECW/TBW was independently associated with CAC (per 0.01 increase of ECW/TBW, odds ratio 1.168, 95% confidence interval, 1.079–1.264, P<0.001). The adjusted R 2 for predicting higher coronary artery calcium scores and CAC significantly improved after ECW/TBW was added to conventional factors. This association was further confirmed by net reclassification and integrated discriminant improvements, sensitivity analysis, and subgroup analysis.Conclusions ECF status is independently associated with a high risk of CAC in patients with CKD.Study Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02003781.

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Extracellular overhydration linked with endothelial dysfunction in the context of inflammation in haemodialysis dependent chronic kidney disease

Cited by 55 publications

References 62 publications

Body Fluids in End-Stage Renal Disease: Statics and Dynamics

Body Fluids in End-Stage Renal Disease: Statics and Dynamics

Independent Association of Overhydration with All-Cause and Cardiovascular Mortality Adjusted for Global Left Ventricular Longitudinal Systolic Strain and E/E’ Ratio in Maintenance Hemodialysis Patients

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease

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