Microvascular perfusion, perfused boundary region and glycocalyx shedding in patients with autosomal dominant polycystic kidney disease: results from the GlycoScore III study

Abstract

Background Vascular abnormalities and endothelial dysfunction are part of the spectrum of autosomal dominant polycystic kidney disease (ADPKD). The mechanisms behind these manifestations including potential affection of the endothelial surface layer (ESL) and glycocalyx integrity remain unknown. Methods Forty-five ambulatory adult patients with ADPKD were enrolled in this prospective, observational, cross-sectional, single-centre study. Fifty-one healthy volunteers served as a control group. All participants underwent real-time microvascular perfusion measurements of the sublingual microcirculation using sidestream dark field imaging. After image acquisition, the perfused boundary region (PBR), an inverse parameter for red blood cell (RBC) penetration into the ESL, was automatically calculated. Microvascular perfusion was assessed by RBC filling and capillary density. Concentrations of circulating glycocalyx components were determined by ELISA. Results ADPKD patients showed a significantly higher PBR compared to healthy controls (2.09±0.23 µm vs. 1.79±0.25 µm, p<0.001). This was accompanied by a significantly lower RBC filling (70.4±5.0% vs. 77.9±5.4%, p<0.001) as well as a higher valid capillary density (318 [269 – 380] n/mm² vs. 273 [230 – 327 n/mm²], p = 0.007). Significantly higher plasma concentrations of heparan sulphate (1625±807 ng/mL vs. 1329±316 ng/mL, p = 0.034), hyaluronan (111 [79 – 132] vs. 92 [82 – 98] ng/mL, p = 0.042) and syndecan-1 were noted in ADPKD patients compared to healthy controls (35 [27 – 57] vs. 29 [23 – 42] ng/mL, p = 0.035). Conclusions Dimensions and integrity of the ESL are impaired in ADPKD patients. Increased capillary density may be a compensatory mechanism for vascular dysfunction to ensure sufficient tissue perfusion and oxygenation.

Plasma glycocalyx pattern: a mirror of endothelial damage in chronic kidney disease

“…Patients with autosomal dominant polycystic kidney disease have a thinner glycocalyx than healthy people. They also have higher levels of plasma hyaluronan and syndecan-1 [ 41 ]. The lack of information on the role played by decorin and perlecan (EG molecules implicated in atherosclerotic plaque development [ 31–33 ]) in CKD motivated us to study these molecules as possible markers of endothelial damage.…”