Accessible Requires Authentication Published by De Gruyter October 19, 2020

Urine soluble CD163 (sCD163) as biomarker in glomerulonephritis: stability, reference interval and diagnostic performance

Anne J. Nielsen, Marlene C. Nielsen, Henrik Birn, Per Ivarsen, Holger J. Møller and Claus V. B. Hviid

Abstract

Objectives

Soluble (s) CD163 is a well-established macrophage biomarker, and recent data suggests urine sCD163 to reflect disease activity in crescentic glomerulonephritis (GN). Other types of GN may also be associated with glomerular inflammation but the potential usefulness of urine sCD163 as a general biomarker of GN remains unaddressed.

Methods

An in-house sCD163 enzyme-linked immunosorbent assay (ELISA) was validated for urinary use and compared to a frequently used commercial ELISA. The pre-analytical stability of urine sCD163 was assessed and a reference interval was established according to the CLSI guidelines using specimens from 253 healthy individuals. Urine samples from 64 patients with different types of renal disorders were also analysed.

Results

Urine sCD163 was highly stable during storage. An upper reference limit of 5.1 μg/L (1.9 μg/mmol, normalised to creatinine) was established using the in-house ELISA. Urine sCD163 was generally increased in GN patients (3.9 μg/mmol, p<0.0001, AUROC=0.97) and decreased upon treatment, but did not perform better than urine albumin (AUROC=1.00). Patients with proliferative GN had higher urine sCD163/albumin (p=0.0001) ratio. The commercial assay had a higher detection limit, and patient levels were 4–6 times lower than in the in-house assay.

Conclusions

Urine sCD163 is a stable biomarker that can be measured with acceptable accuracy using our in-house ELISA. Its pre-analytical characteristics makes it a reliable biomarker and our findings point towards the use of urine sCD163 as a biomarker of specific subtypes of GN.


Corresponding author: Holger Jon Møller, MD, PhD, DMSci, Department of Clinical Biochemistry, Aarhus University Hospital, Palle-Juul Jensens Boulevard 99, DK-8200, Aarhus, Denmark, E-mail:

Funding source: Nyreforeningens Forskningsfond

Funding source: P.A Messerschmidt og Hustru Fond

Funding source: Helen og Ejnar Bjørnows Fond

Acknowledgments

The authors wish to thank Helle Hauser Ryom, Christina Strande Sønderskov, and Lene Dabelstein for exceptional technical assistance.

  1. Research funding: The study was supported by Helen & Ejnar Bjørnows Fond, P.A. Messerschmidt og Hustru Fond and Nyreforeningens Forskningsfond.

  2. Author contributions: AJN, MCN, HB, PI, HJM, CVBH: Conception and study design. HB, PI: Inclusion of patients. AJN, PI, CVBH: Collection of data. AJN, MCN, HB, PI, HJM, CVBH: Analysis and interpretation of data. AJN, MCN, HB, PI, HJM, CVBH: Revising the manuscript critically. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The analysis of collected urine specimens from patients enrolled at the Department of Renal Medicine, Aarhus University Hospital, was approved by the Regional Ethics Committee (VEK 1-10-72-378-17) and the Data Protection Agency (2012-41-0561).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-0466).

Received: 2020-04-07
Accepted: 2020-09-27
Published Online: 2020-10-19
Published in Print: 2021-03-26

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