Biomarkers of fibrosis, kidney tissue injury and inflammation may predict severity and outcome of renal ANCA - associated vasculitis

Veronika Satrapova; Nadja Sparding; Federica Genovese; Morten Asser Karsdal; Lenka Bartonova; Doubravka Frausova; Eva Honsova; Marek Kollar; Miloslav Suchanek; Helena Koprivova; Romana Rysava; Vladimira Bednarova; Vladimir Tesar; Zdenka Hruskova

doi:10.3389/fimmu.2023.1122972

Biomarkers of fibrosis, kidney tissue injury and inflammation may predict severity and outcome of renal ANCA - associated vasculitis

Front Immunol. 2023 Mar 20:14:1122972. doi: 10.3389/fimmu.2023.1122972. eCollection 2023.

Affiliations

¹ Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia.
² Nordic Bioscience, Herlev, Denmark.
³ Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czechia.
⁴ Faculty of Environment, Jan Evangelista Purkyně University in Ústí nad Labem, Ústí nad Labem, Czechia.
⁵ Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia.

Abstract

Background: Activity and chronicity of kidney involvement in ANCA-associated vasculitis (AAV) can be currently reliably evaluated only by kidney biopsy. In this study, we measured a panel of serum and urinary biomarkers collected at the time of kidney biopsy and hypothesized that they could reflect specific histopathological parameters in the biopsy and help to predict prognosis.

Methods: We examined a cohort of 45 patients with AAV and 10 healthy controls. Biomarker levels (DKK-3, CD163, EGF, PRO-C6 and C3M) were measured in this study by ELISA. Biopsies were scored with a scoring system for AAV (focal x crescentic x sclerotic x mixed class) and interstitial fibrosis was quantified.

Results: Levels of urinary DKK-3, CD163, EGF, PRO-C6 and C3M significantly differed among biopsy classes in AAV, with urinary DKK-3 and PRO-C6 levels being highest in the sclerotic class and lowest in the focal class, urinary CD163 levels highest in the crescentic class and urinary C3M levels highest in the focal class. Moreover, the urinary biomarkers were able to discriminate focal biopsy class from the other classes. Urinary DKK-3, EGF, PRO-C6 and C3M levels measured at the time of biopsy were also significantly related to the extent of fibrosis and to the final kidney function at the end of follow-up.

Conclusions: This small pilot study suggests that selected urinary biomarkers of fibrosis and inflammation may reflect changes in the kidney biopsy and be prognostic of kidney outcome in patients with AAV.

Keywords: ANCA- associated vasculitis; DKK-3; PRO-C6; biomarkers; chronic kidney disease; kidney biopsy; kidney fibrosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis* / pathology
Antibodies, Antineutrophil Cytoplasmic*
Biomarkers / urine
Epidermal Growth Factor
Fibrosis
Humans
Inflammation / pathology
Kidney / pathology
Pilot Projects

Substances

Antibodies, Antineutrophil Cytoplasmic
Epidermal Growth Factor
Biomarkers

Grants and funding

The authors thank the following for financial support: Ministry of Health, Czech Republic – conceptual development of research organization 00064165, General University Hospital in Prague and Ministry of Education, Czech Republic, grant Cooperatio 207034 Internal disciplines. Nordic Bioscience provided support in the form of salaries for authors NS, FG, and MK but did not have any additional role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.