Assay-related differences in SuPAR levels: implications for measurement and data interpretation
Open accessPublished version of a preprint
Abstract
ABSTRACT With the growing interest in studying the role of soluble urokinase plasminogen activator receptor (suPAR) in kidney and other diseases, levels are now being measured in major cohorts across the world through various methods, including immunoassays and through proteomics. Reported suPAR values have however varied dramatically depending on which assay is used. Comparing suPAR assays and their ability to discriminate risk is crucial for the Nephrology and overall research community to guide assay choice and inform interpretation of findings. To that end we measured suPAR in 3 different major cohorts (Malmo Diet and Cancer Study, n=4637; Jackson Heart Study, n=1905; and the Emory Cardiovascular Biobank, n=487) using two different methods in each cohort, encompassing the most commonly used approaches (immunoassays and proteomics). We find dramatic differences between assays; with notably poor correlations between immunoassays and proteomic approaches (r=0.2-0.5). Proteomics-based suPAR measures very poor discriminatory ability for cardiovascular and incident kidney disease. Amongst the immunoassays, the suPARnostic assay reported the highest values and had the strongest discriminatory ability.
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Failure to detect and account for such genetic variation may challenge the interpretation of results obtained across ancestries and introduce a source of bias.
“Failure to detect and account for such genetic variation may challenge the interpretation of results obtained across ancestries and introduce a source of bias21.”
From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [21]
The discussion (page not provided) identifies single-nucleotide polymorphisms that alter assay-binding affinity as a measurement limitation and urges caution when interpreting suPAR results. It does not say that failure to account for genetic variation biases comparisons across ancestries; that ancestry-specific extension is unsupported by our copy. (LLM, conf=0.84)
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Cites
Comparison of Proteomic Assessment Methods in Multiple Cohort Studies
Raffield, L. M., Dang, H., Pratte, K. A., Jacobson, S., Gillenwater, L. A., Ampleford, E., Barjaktarevic, I., Basta, P., Clish, C. B., Comellas, A. P., et al. (2020) · PROTEOMICS · doi:10.1002/pmic.201900278 · Cited by 184 · see citing works
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Research works printed but not linked: 4
- [1]Hayek SS Sever S Ko YA Trachtman H Awad M Wadhwani S Soluble urokinase receptor and chronic kidney disease N Engl J Med 2015 373 20 1916 1925 10.1056/NEJMoa1506362 26539835 PMC4701036 · DOI
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- [4]Winnicki W Sunder-Plassmann G Sengolge G Handisurya A Herkner H Kornauth C Diagnostic and prognostic value of soluble urokinase-type plasminogen activator receptor (suPAR) in Focal segmental glomerulosclerosis and impact of detection method Sci Rep 2019 9 1 13783 10.1038/s41598-019-50405-8 31551522 PMC6760112 · DOI
- [5]Abraham AG Xu Y Roem JL Greenberg JH Weidemann DK Sabbisetti VS Variability in CKD biomarker studies: suPAR and kidney disease progression in the chronic kidney disease in children (CKiD) study Kidney Med 2021 5 3 P712 P721 10.1016/j.xkme.2021.04.007 PMC8515077 34693253 · DOI
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Cross-ancestry comparison of aptamer and antibody protein measures
Nicholas, J. C., Katz, D. H., Tahir, U. A., Debban, C. L., Aguet, F., Blackwell, T., Bowler, R. P., Broadaway, K. A., Chen, J., Clish, C. B., et al. (2026) · Nature Communications · doi:10.1038/s41467-025-67814-1 · Cited by 13 · see citing works
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- Authors
- Vasbinder, A., Raffield, L. M., Gao, Y., Engstrom, G., Quyyumi, A. A., Reiner, A. P., Reiser, J., & Hayek, S. S.
- Affiliations
- University of Michigan (US)
- University of North Carolina at Chapel Hill (US)
- University of Mississippi Medical Center (US)
- Department of Clinical Sciences, Lund University, Malmö, Sweden 4
- Emory University (US)
- Department of Epidemiology, University of Washington, Seattle, WA, USA 6
- Rush University Medical Center (US)
- Corresponding author
- Hayek, Salim Salim
- Venue
- Journal of Nephrology
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-05-14
- Volume
- 36
- Issue
- 1
- Pages
- 157-159
- ISSN
- 1121-8428 (ISSN-L)
- 1724-6059
- PMC
- PMC9106999
- OpenAlex
- W4280529751
- Cited by
- 21
- References
- 1
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 2
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nephrology (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL153384, T32-HL007853, T32HL129982, R01HL132947)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01-DK119083, R01-DK109720)
- University of Michigan Frankel Cardiovascular Center (U-M G024231)
- National Center for Advancing Translational Sciences (KL2TR002490)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- soluble urokinase plasminogen activator receptor, suPAR, assay variability, measurement standardization, data interpretation, biomarkers, acute kidney injury
- MeSH terms
- Humans, Biomarkers, Receptors, Urokinase Plasminogen Activator
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