Damage of the Endothelial Glycocalyx in Dialysis Patients

Vlahu, Carmen A.; Lemkes, Bregtje A.; Struijk, Dirk G.; Koopman, M. G.; Krediet, Raymond T.; Vink, Hans

doi:10.1681/asn.2011121181

Cited by 228 publications

(256 citation statements)

References 53 publications

(49 reference statements)

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“…There have been only two studies evaluating syndecan-1 levels in patients with renal disease. 21 In one study, patients undergoing maintenance hemodialysis had higher levels of syndecan-1 than controls. The other study excluded any accumulation effect of syndecan-1 into the circulation because of reduced renal clearance, 22 and thus, it is unlikely that only the reduced GFR may be responsible for the increase in syndecan levels.…”

Section: Discussionmentioning

confidence: 98%

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Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Libório¹,

Braz²,

Seguro³

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P 0.001) and syndecan-1 (73.7 ± 15.9 versus 21.2 ± 7.9 ng/mL, P 0.001) compared with exposed controls. Patients with leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinaseassociated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKIassociated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage.

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Section: Discussionmentioning

confidence: 98%

“…In the end, 46 patients were included in the final analysis. All patients were male and between 18 and 24 years old, with a median age of 21 (19)(20)(21)(22)(23) years. No patient had any comorbidity, and all patients had a basal eGFR higher than 80 mL/min.…”

Section: Methodsmentioning

confidence: 99%

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Libório¹,

Braz²,

Seguro³

et al. 2015

The American Society of Tropical Medicine and Hygiene

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“…It was shown recently that dialysis patients have an impaired glycocalyx barrier, where its constituents are shed into the blood. 53 In the setting of CKD, several factors may contribute to the alteration of the endothelial glycocalyx, but the exact responsible mechanisms have, until now, only partially been elucidated. A chronic inflammatory status and increased oxidative stress, both associated with vascular dysfunction in CKD, contribute to severe atherosclerosis and cardiovascular morbidity and mortality in these patients, 3,54-56 but they have also been linked to glycocalyx disruption.…”

Section: Discussionmentioning

confidence: 99%

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Pletinck

Glorieux

Schepers

et al. 2013

Journal of the American Society of Nephrology

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Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.

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“…[30][31][32] Great variability in systemic ESL volume has been reported between different medical conditions, regardless of how ESL volume was estimated. [33][34][35] Mean systemic ESL volume in healthy individuals was shown to be 1.5-1.7 L, whereas much lower systemic ESL volumes were found in treated (1.1 L) and untreated (0.8 L) patients with heterozygous familial hypercholesterolemia and normoalbuminuric (0.8 L) and microalbuminuric (0.2 L) patients with type 1 diabetes. 33,34 Elevated shedding products, reflecting ESL breakdown, have been found in patients with severe sepsis, CKD, or ESRD, patients on dialysis, patients after major vascular surgery, and patients during acute or chronic hyperglycemia.…”

mentioning

confidence: 95%

Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

Engberink

Rorije

Heide

et al. 2015

Journal of the American Society of Nephrology

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Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycosaminoglycans in the skin interstitium, where sodium is bound to glycosaminoglycans without commensurate effects on extracellular volume. The endothelial surface layer is a dynamic layer on the luminal side of the endothelium that is in continuous exchange with flowing blood. Because negatively charged glycosaminoglycans are abundantly present in this layer, it may act as an intravascular buffer compartment that allows sodium to be transiently stored. This review focuses on the putative role of the endothelial surface layer as a contributor to salt sensitivity, the consequences of a perturbed endothelial surface layer on sodium homeostasis, and the endothelial surface layer as a possible target for the treatment of hypertension and an expanded extracellular volume. J Am Soc Nephrol 26: 777-783, 2015. doi: 10.1681 In Western society, average daily intake of salt is 8-12 g, thereby greatly exceeding the recommended amount by the World Health Organization of 5 g daily. 1,2 This recommendation is on the basis of the observation that dietary salt intake exceeding 5 g/d, which is equivalent to 2 g or 85 mmol sodium, is associated with hypertension and increased cardiovascular risk in many cohort studies. 3,4 Other than negative effects on cardiovascular morbidity and mortality, high salt intake has also been related to intermediate end points for kidney damage, such as proteinuria, in both patients with CKD and the general population. 5,6 Dietary salt restriction is, therefore, regarded as an important target for improvement of global health. 4 For example, in the United States, it has been estimated that a reduction of dietary salt intake by 3 g/d would reduce annual health costs by $10-$24 billion. 7 Generally, detrimental effects of excessive sodium intake have been linked to expansion of extracellular volume (ECV) and hypertension, which is evidenced by various observations that low sodium reduces BP in both normotensive individuals and individuals with hypertension. 4,8 The increase in BP after dietary sodium excess is highly variable, with some individuals showing a relatively small increase, whereas large BP increases can be observed in others. 9,10 It is likely that these individual variations in salt sensitivity differentially affect cardiovascular and renal risk and may also explain the inconsistent results from population studies investigating the relation between sodium intake and cardiovascular risk. 11 According to Guyton's pressurenatriuresis curve, the kidney regulates long-term BP by altering renal sodium e...

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Damage of the Endothelial Glycocalyx in Dialysis Patients

Cited by 228 publications

References 53 publications

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

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