The relationship between circulating endothelial microparticles and arterial stiffness and atherosclerosis in children with chronic kidney disease

Dursun, İsmail; Poyrazoğlu, Hakan; Gündüz, Zübeyde; Ülger, Harun; Yykylmaz, Ali; Düşünsel, Ruhan; Patyroglu, Turkan; Gürgöze, Metin Kaya

doi:10.1093/ndt/gfp066

Cited by 89 publications

(88 citation statements)

References 52 publications

(86 reference statements)

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“…75 This is in line with other studies. 76,77 In particular, elevated EMPs were associated with endothelial damage in renal failure. The effect of the uremic milieu on MPs is supported by in vitro experiments showing that uremic toxins (such as indoxyl sulfate and p-cresyl sulfate) directly induced release of EMPs.…”

Section: Ckd/uremia/esrdmentioning

confidence: 99%

Extracellular Vesicles in Renal Diseases

Erdbrügger

2016

Journal of the American Society of Nephrology

165

174

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Extracellular vesicles from the urine and circulation have gained significant interest as potential diagnostic biomarkers in renal diseases. Urinary extracellular vesicles contain proteins from all sections of the nephron, whereas most studied circulating extracellular vesicles are derived from platelets, immune cells, and the endothelium. In addition to their diagnostic role as markers of kidney and vascular damage, extracellular vesicles may have functional significance in renal health and disease by facilitating communication between cells and protecting against kidney injury and bacterial infection in the urinary tract. However, the current understanding of extracellular vesicles has derived mostly from studies with very small numbers of patients or in vitro data. Moreover, accurate assessment of these vesicles remains a challenge, in part because of a lack of consensus in the methodologies to measure extracellular vesicles and the inability of most techniques to capture the entire size range of these vesicles. However, newer techniques and standardized protocols to improve the detection of extracellular vesicles are in development. A clearer understanding of the composition and biology of extracellular vesicles will provide insights into their pathophysiologic, diagnostic, and therapeutic roles.

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Section: Ckd/uremia/esrdmentioning

confidence: 99%

Extracellular Vesicles in Renal Diseases

Erdbrügger

2016

Journal of the American Society of Nephrology

165

174

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“…Endothelial MPs are markers for vascular dysfunction in CKD and possible causes of thrombosis and cardiovascular diseases (83,84). High levels of extracellular phosphate induce MP production in cultured endothelial cells (85).…”

Section: Phosphate and Cardiovascular Diseasementioning

confidence: 99%

Phosphate Toxicity in CKD: The Killer among Us

Ritter¹,

Slatopolsky²

2016

CJASN

111

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Maintenance of a normal serum phosphate level depends on absorption in the gut, reabsorption and excretion by the kidney, and the flux between the extracellular and skeletal pools. Phosphate homeostasis is a coordinated, complex system of crosstalk between the bone, intestine, kidney, and parathyroid gland. Dysfunction of this system has serious clinical consequences in healthy individuals and those with conditions, such as CKD, in which hyperphosphatemia is associated with increased risks of cardiovascular morbidity and mortality. The last halfcentury of renal research has helped define the contribution of the parathyroid hormone, calcitriol, fibroblast growth factor 23, and Klotho in the regulation of phosphate. However, despite new discoveries and insights gained during this time, what remains unchanged is the recognition that phosphate retention is the initiating factor for the development of many of the complications observed in CKD, namely secondary hyperparathyroidism and bone and cardiovascular diseases. Controlling phosphate load remains the primary goal in the treatment of CKD. This review discusses the clinical effects of dysregulated phosphate metabolism, particularly in CKD, and its association with cardiovascular disease. The importance of early control of phosphate load in the treatment of CKD is emphasized, and the latest research in the treatment of phosphate retention is discussed.

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“…In CKD, higher circulating levels of EMP have been found in haemodialysis patients compared to pre-dialysis CKD, peritoneal dialysis and healthy controls [21][22][23] . In haemodialysis patients, EMPs and other microparticles have been shown to correlate with arterial vascular stiffness measured by PWV and augmentation index (AIx) [24] .…”

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confidence: 99%

The Association of Baseline and Longitudinal Change in Endothelial Microparticle Count with Mortality in Chronic Kidney Disease

Green¹,

Skeoch

Alexander

et al. 2017

Nephron

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Background: Chronic kidney disease (CKD) is associated with a unique milieu of vascular pathology, and effective biomarkers of active vascular damage are lacking. A candidate biomarker is the quantification of circulating endothelial microparticles (EMPs). This study observed baseline and longitudinal EMP change (δEMP) and established the association of these with all-cause mortality and cardiovascular events in CKD. Method: An observational study in adults with CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²). EMPs were quantified by flow cytometry of platelet poor plasma in 2 samples 12 months apart and categorised as EMP if AnnexinV+/CD31+/CD42b- EMPs were compared between primary renal diagnoses, and correlations between EMP/δEMP and other parameters made. Adjusted hazard ratios (HRs) for time to all-cause mortality and cardiovascular events were calculated for log-transformed EMP and δEMP using a Cox proportional hazard model. Results: There were 123 patients (age 63 ± 11 years, systolic blood pressure 135 ± 18 mm Hg, eGFR 32 ± 16 mL/min/1.73 m²). The median baseline EMP count was 144/μL (range 10-714/μL). EMPs were numerically the highest in autosomal dominant polycystic kidney disease (253 [41-610]). An increase in urine protein:creatinine ratio was associated with an increase in EMP (co-efficient 0.21, p = 0.02). The adjusted HR for all-cause mortality for EMP was 8.20 (1.67-40.2, p = 0.01) and for δEMP was 2.69 (0.04-165, p = 0.64). There was no association between EMP or δEMP and cardiovascular events. Conclusion: Although EMP count was a significant marker of mortality risk, longitudinal change was not. This may reflect disease-specific EMP behaviour and the limitation of EMP as a generalised biomarker in CKD.

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The relationship between circulating endothelial microparticles and arterial stiffness and atherosclerosis in children with chronic kidney disease

Abstract: Our results suggest that endothelial damage starts in the early stage of CKD, that the endothelial dysfunction becomes overt with the increase of cardiovascular risk factors and that EMPs may be a reliable marker of the subclinical atherosclerosis and arterial stiffness.

Cited by 89 publications

References 52 publications

Extracellular Vesicles in Renal Diseases

Extracellular Vesicles in Renal Diseases

Phosphate Toxicity in CKD: The Killer among Us

The Association of Baseline and Longitudinal Change in Endothelial Microparticle Count with Mortality in Chronic Kidney Disease

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