Dataset Information

Association of kidney function with changes in the endothelial surface layer.

ABSTRACT:

Background and objectives

ESRD is accompanied by endothelial dysfunction. Because the endothelial glycocalyx (endothelial surface layer) governs interactions between flowing blood and the vessel wall, perturbation could influence disease progression. This study used a novel noninvasive sidestream-darkfield imaging method, which measures the accessibility of red blood cells to the endothelial surface layer in the microcirculation (perfused boundary region), to investigate whether renal function is associated with endothelial surface layer dimensions.

Design, setting, participants, & measurements

Perfused boundary region was measured in control participants (n=10), patients with ESRD (n=23), participants with normal kidney function after successful living donor kidney transplantation (n=12), and patients who developed interstitial fibrosis/tubular atrophy after kidney transplantation (n=10). In addition, the endothelial activation marker angiopoietin-2 and shed endothelial surface layer components syndecan-1 and soluble thrombomodulin were measured using ELISA.

Results

Compared with healthy controls (1.82 ± 0.16 µm), ESRD patients had a larger perfused boundary region (+0.23; 95% confidence interval, 0.46 to <0.01; P<0.05), which signifies loss of endothelial surface layer dimensions. This large perfused boundary region was accompanied by higher circulating levels of syndecan-1 (+57.71; 95% confidence interval, 17.38 to 98.04; P<0.01) and soluble thrombomodulin (+12.88; 95% confidence interval, 0.29 to 25.46; P<0.001). After successful transplantation, the perfused boundary region was indistinguishable from healthy controls (without elevated levels of soluble thrombomodulin or syndecan-1). In contrast, however, patients who developed interstitial fibrosis and tubular atrophy showed a large perfused boundary region (+0.36; 95% confidence interval, 0.09 to 0.63; P<0.01) and higher levels of endothelial activation markers. In addition, a significant correlation between perfused boundary region, angiopoietin-2, and eGFR was observed (perfused boundary region versus GFR: Spearman's ?=0.31; P<0.05; perfused boundary region versus angiopoietin-2: Spearman's ?=-0.33; P<0.05).

Conclusion

Reduced renal function is strongly associated with low endothelial surface layer dimensions. After successful kidney transplantation, the endothelial surface layer is indistinguishable from control.

SUBMITTER: Dane MJ

PROVIDER: S-EPMC3974363 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Publications

Association of kidney function with changes in the endothelial surface layer.

Dane Martijn J C MJ Khairoun Meriem M Lee Dae Hyun DH van den Berg Bernard M BM Eskens Bart J M BJ Boels Margien G S MG van Teeffelen Jurgen W G E JW Rops Angelique L W M M AL van der Vlag Johan J van Zonneveld Anton Jan AJ Reinders Marlies E J ME Vink Hans H Rabelink Ton J TJ

Clinical journal of the American Society of Nephrology : CJASN 20140123 4

<h4>Background and objectives</h4>ESRD is accompanied by endothelial dysfunction. Because the endothelial glycocalyx (endothelial surface layer) governs interactions between flowing blood and the vessel wall, perturbation could influence disease progression. This study used a novel noninvasive sidestream-darkfield imaging method, which measures the accessibility of red blood cells to the endothelial surface layer in the microcirculation (perfused boundary region), to investigate whether renal fu ...[more]

PMID: 24458084

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Project description:BackgroundThe mechanisms linking cardiovascular autonomic neuropathy, diabetic kidney disease and cardiovascular mortality in type 2 diabetes are widely unknown. We investigated the relationship between baseline cardiovascular autonomic function and changes in kidney and myocardial function over six years in patients with type 2 diabetes and healthy controls.MethodsPost-hoc analysis of a cohort study in 24 patients with type 2 diabetes and 18 healthy controls. Baseline determinants were cardiovascular autonomic reflex tests (heart rate response to: standing (30:15); deep breathing (E:I); and the Valsalva test) and time- and frequency-domain heart rate variability indices. Outcomes were changes in estimated glomerular filtration rate (eGFR), albuminuria, myocardial flow reserve (MFR) measured by cardiac 82Rb Positron emission tomography computed tomography (PET/CT), and coronary artery calcium score (CACS).ResultsMean age at inclusion was 61 ± 10 years and 36% were female. Mean follow up time was 6 ± 0 years. A lower response in heart rate to the Valsalva test (corresponding to weaker autonomic function) was associated with a larger decline in eGFR (p=0.04), but not significantly after adjustment for sex, baseline age, smoking status, systolic blood pressure, heart rate, HbA1c, body mass index and baseline eGFR (p=0.12). A higher baseline response in heart rate to standing (30:15) was associated with a larger decline in myocardial flow reserve in the unadjusted analysis (p=0.02) and after adjustment (p=0.02). A higher response in heart rate to the Valsalva maneuver was associated with a larger increase in CACS (p = 0.02), but the association became insignificant after adjustment (p = 0.16).ConclusionA lower response in heart rate to the Valsalva test was associated with a larger decline in kidney function, indicating that autonomic dysfunction may predict future loss of kidney function. However, we did not find any association between lower values in cardiovascular autonomic function at baseline and a worsening in albuminuria, myocardial function, or atherosclerotic burden.

Project description:BackgroundSarcopenia and endothelial dysfunction are both common among kidney transplant (KT) recipients. We aimed to evaluate the association between endothelial dysfunction and sarcopenia, as well as its individual components.MethodsVascular reactivity index (VRI), skeletal muscle index (SMI = skeletal muscle mass/height2), handgrip strength (HGS), and 6-meter usual gait speed (GS) were measured in 95 KT recipients. Low SMI was defined as SMI less than 10% of the sex-specific reference values from Chinese adults; low HGS as HGS < 28 kg for men and < 18 kg for women; slow GS as GS below 1.0 m/s. Sarcopenia was diagnosed based on the presence of low SMI as an essential criterion, accompanied by either low HGS or slow GS. Vascular reactivity was classified as being indicative of poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), or good (VRI ≥ 2.0) vascular reactivity.ResultsOf the 95 patients, aged 45.2 ± 10.9 years, 11.6% had sarcopenia and 13.7% had poor vascular reactivity. Patients with sarcopenia were lower in body mass index (p = 0.001) and VRI (p = 0.041), and have a higher proportion of low muscle mass (p < 0.001), low HGS (p < 0.001), and slow GS (p = 0.001). Patients with poor vascular reactivity have a higher proportion of sarcopenia (p = 0.005), low HGS (p = 0.006), and slow GS (p = 0.029). Multivariate logistic regression analysis showed that patients in the poor VRI group were significantly associated with sarcopenia (odds ratio, OR = 6.17; 95% confidence interval [1.06-36.04]; p = 0.043), comparing to those with good VRI. We further analysed the effects of VRI on individual components of sarcopenia and found that VRI predicted slow GS significantly (OR = 0.41; 95% CI = [0.21-0.79]; p = 0.007), but not low SMI (OR = 1.15; 95% CI [0.53-2.49]; p = 0.718) and HGS (OR = 0.59; 95% CI [0.31-1.16]; p = 0.125).ConclusionsWe concluded that endothelial dysfunction is a key determinant of sarcopenia in KT recipients. Furthermore, endothelial dysfunction is more closely related to gait speed than muscle mass and strength.

Dataset Information

Association of kidney function with changes in the endothelial surface layer.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusion

Publications

Association of kidney function with changes in the endothelial surface layer.

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