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

Alexander Fuchs; Jennifer Dederichs; Sita Arjune; Polina Todorova; Fabian Wöstmann; Philipp Antczak; Anja Illerhaus; Birgit Gathof; Franziska Grundmann; Roman-Ulrich Müller; Thorsten Annecke

doi:10.1093/ckj/sfac229

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

Clin Kidney J. 2022 Oct 19;16(2):384-393. doi: 10.1093/ckj/sfac229. eCollection 2023 Feb.

Authors

Affiliations

¹ University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department of Anaesthesiology and Intensive Care Medicine, Cologne, Germany.
² University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department II of Internal Medicine and Center for Molecular Medicine Cologne, Cologne, Germany.
³ University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department of Dermatology, Cologne, Germany.
⁴ University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute of Transfusion Medicine, Cologne, Germany.
⁵ CECAD, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
⁶ University of Witten/Herdecke, Anaesthesiology II, Kliniken der Stadt Köln gGmbH, Department of Anaesthesiology and Intensive Care Medicine, Merheim Medical Center, Cologne, Germany.

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 effects on 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 enzyme-linked immunosorbent assay.

Results: ADPKD patients showed a significantly larger PBR compared with healthy controls (2.09 ± 0.23 µm versus 1.79 ± 0.25 µm; P < .001). This was accompanied by significantly lower RBC filling (70.4 ± 5.0% versus 77.9 ± 5.4%; P < .001) as well as a higher valid capillary density {318/mm² [interquartile range (IQR) 269-380] versus 273/mm² [230-327]; P = .007}. Significantly higher plasma concentrations of heparan sulphate (1625 ± 807 ng/ml versus 1329 ± 316 ng/ml; P = .034), hyaluronan (111 ng/ml [IQR 79-132] versus 92 ng/ml [82-98]; P = .042) and syndecan-1 were noted in ADPKD patients compared with healthy controls (35 ng/ml [IQR 27-57] versus 29 ng/ml [23-42]; P = .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.

Keywords: ADPKD; endothelium; glycocalyx; intravital microscopy; microcirculation.