Universität zu Köln

Fuchs, Alexander ORCID: 0000-0002-6543-5051, Dederichs, Jennifer, Arjune, Sita ORCID: 0000-0002-6121-4614, Todorova, Polina ORCID: 0000-0002-4728-224X, Woestmann, Fabian, Antczak, Philipp, Illerhaus, Anja ORCID: 0000-0003-0521-203X, Gathof, Birgit, Grundmann, Franziska, Mueller, Roman-Ulrich and Annecke, Thorsten (2023). 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., 16 (2). S. 384 - 394. OXFORD: OXFORD UNIV PRESS. ISSN 2048-8513

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Abstract

Lay Summary Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to kidney failure. However, ADPKD not only affects the kidney, but also involves other organ systems, including the vasculature. The pathogenesis of vascular disease is not well understood. Here we examined changes in the inner-most layer of blood vessels in ADPKD patients and found significant alterations of the endothelial surface layer (ESL). Considering the importance of the ESL in the integrity of vascular function, this finding is of great interest for ADPKD research. 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 mu m versus 1.79 +/- 0.25 mu m; 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/mm(2) [interquartile range (IQR) 269-380] versus 273/mm(2) [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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fuchs, Alexander UNSPECIFIED orcid.org/0000-0002-6543-5051 UNSPECIFIED Dederichs, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Arjune, Sita UNSPECIFIED orcid.org/0000-0002-6121-4614 UNSPECIFIED Todorova, Polina UNSPECIFIED orcid.org/0000-0002-4728-224X UNSPECIFIED Woestmann, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Antczak, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Illerhaus, Anja UNSPECIFIED orcid.org/0000-0003-0521-203X UNSPECIFIED Gathof, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Grundmann, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Roman-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Annecke, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-672499
DOI:	10.1093/ckj/sfac229
Journal or Publication Title:	Clin. Kidney J.
Volume:	16
Number:	2
Page Range:	S. 384 - 394
Date:	2023
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	2048-8513
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GLYCOCALYX; DAMAGE; DYSFUNCTION; DENSITY Multiple languages Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67249