Serum Copeptin, NLPR3, and suPAR Levels among Patients with Autosomal-Dominant Polycystic Kidney Disease with and without Impaired Renal Function

Abstract

Background: The pathophysiology of renal disease progression in autosomal-dominant polycystic kidney disease (ADPKD) involves not only cystogenesis but also endothelial dysfunction, leading to the activation of inflammatory and fibrotic pathways. This study evaluated the levels of biomarkers related to osmoregulation, immune system activation, and tubular injury in ADPKD patients with impaired or preserved renal function. Methods: This study included 26 ADPKD patients with modestly impaired renal function (estimated glomerular filtration rate [eGFR] 45–70 mL/min/1.73 m²; Group A), 26 age- and sex-matched ADPKD patients with relatively preserved renal function (eGFR >70 mL/min/1.73 m²; Group B), and 26 age- and sex-matched controls (Group C). Serum levels of copeptin, the inflammasome nucleotide-binding and oligomerization domain-like receptors pyrin domain-containing protein 3 (NLRP3), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured with ELISA techniques. Results: Patients in Group A had higher levels of copeptin (median [interquartile range]: 50.44 [334.85] pg/mL), NLRP3 (5.86 [3.89] ng/mL), and suPAR (390.05 [476.53] pg/mL) compared to patients in Group B (32.38 [58.33], p = 0.042; 2.42 [1.96], p < 0.001; and 313.78 [178.85], p = 0.035, respectively) and Group C (6.75 [6.43]; 1.09 [0.56]; and 198.30 [28.53], respectively; p < 0.001 for all comparisons). Levels of all studied markers were also significantly higher in Group B patients compared to controls ( p < 0.001), despite having similar eGFR. In patients with ADPKD, all studied biomarkers were correlated positively with asymmetric-dimethylarginine (ADMA) and endocan levels, and negatively with eGFR. ADMA and endocan levels were the only parameters independently associated with increased copeptin levels. Conclusions: This study showed that ADPKD patients with impaired and preserved renal function had higher copeptin, NLRP3, and suPAR levels than controls. Such findings support that cystogenesis and inflammation are associated with endothelial dysfunction, even in the early stages of ADKPD.

Journal

Journal ID (publisher-id): CRM

Journal ID (nlm-ta): Cardiorenal Med

Journal ID (doi): 10.1159/issn.1664-5502

Title: Cardiorenal Medicine

Publisher: S. Karger AG

ISSN (Print): 1664-3828

ISSN (Electronic): 1664-5502

Publication date Subscription-year: 2020

Publication date (Print): December 2020

Publication date (Electronic): 17 November 2020

Volume: 10

Issue: 6

Pages: 440-451

Affiliations

_aDepartment of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

_bDepartment of Respiratory Medicine, Papanikolaou General Hospital, Thessaloniki, Greece

_cSection of Nephrology and Hypertension, 1st Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

_dDepartment of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom

Author notes

*Pantelis A. Sarafidis, Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 49, GR–54642 Thessaloniki (Greece), [e-mail]

Article

Publisher ID: 510834 Other ID: Cardiorenal Med 2020;10:440–451

DOI: 10.1159/000510834

PubMed ID: 33202410

Copyright statement: © 2020 S. Karger AG, Basel

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Page count

Figures: 3, Tables: 2, Pages: 12

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Categories

Subject: Research Article