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 (1.8260.16 mm), 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 r=0.31; P,0.05; perfused boundary region versus angiopoietin-2: Spearman's r=20.33; 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.

Syndecan-1 in Acute Decompensated Heart Failure – Association With Renal Function and Mortality –

“…33 Although we disclosed no significant increase in patients with stable CKD, our data are not necessarily contradictory to previous findings. Our CKD patients only had a moderate decline in renal function (mean eGFR 47 ml/min/1.73 m 2 ).…”

“…In the cited study, and in accordance with our findings, patients with moderate kidney impairment after renal transplantation (eGFR 22 ml/min/1.73 m 2 ) presented with similar syndecan-1 levels when compared with controls. 33 More interesting is that the syndecan-1 level measured on ED admission has value as a predictor of acute worsening renal function during hospital stay, even after adjusting for other risk factors for AKI in this population, as suggested in other studies. 34 This finding merits consideration for 2 reasons: (1) the importance of glycocalyx damage on the pathophysiology of cardiorenal syndrome and (2) the use of syndecan-1 as a biomarker for the early detection of AKI.…”

Atrasentan Reduces Albuminuria by Restoring the Glomerular Endothelial Glycocalyx Barrier in Diabetic Nephropathy

“…Unfortunately, the long duration of the model, which was required to faithfully replicate changes seen in human diabetic nephropathy, precluded such follow-up studies in STZ-treated animals. This does not, however, detract from the fact that this study corroborates the rationale for the clinical use of ET A selective receptor blockade in diabetic nephropathy; given the systemic nature of loss of the glycocalyx in diabetes, it also provides a mechanism of action that can be monitored noninvasively (44) in patients before and during treatment.…”

A microscopic view on the renal endothelial glycocalyx

“…We demonstrated that patients with renal failure have increased circulating levels of syndecan-1 and thrombomodulin, which was reversed by kidney transplantation (110). Furthermore, renal failure was shown to correlate with increased concentrations of shed hyaluronan (18). Altogether, while several glycocalyx components are shed upon endothelial activation, the exact location, mechanism, and timing of shedding is complex and mostly unknown.…”