Soluble urokinase plasminogen activator receptor across the kidney–cardiometabolic continuum: a systematic review
- 1Division of Nephrology, Department of Medicine, The Second Affiliated Hospital of Wannan Medical University
Abstract
Background: Soluble urokinase plasminogen activator receptor (suPAR), a circulating marker of innate immune activation, has been proposed as a risk biomarker in chronic kidney disease (CKD) and related cardiometabolic conditions, but its clinical utility remains uncertain.
Methods: We performed a systematic review according to PRISMA 2020 and the Synthesis Without Meta-analysis (SWiM) guideline, searching PubMed, Embase, Web of Science, Scopus, the Cochrane Library, medRxiv, ClinicalTrials.gov, and WHO ICTRP from inception to May 15, 2026. Two reviewers independently screened records, extracted data, and assessed quality using the Newcastle-Ottawa Scale, the JBI checklist, RoB 2, and QUADAS-2; certainty of evidence was rated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
Results: Twenty studies comprising 31,416 participants were included. In adults with preserved kidney function, elevated suPAR predicted incident CKD (adjusted odds ratio (OR) 3.13 for the highest versus lowest quartile, 95% confidence interval (CI) 2.11–4.65) and end-stage kidney disease (ESKD) (adjusted hazard ratio (HR) 1.53 for the highest versus lowest tertile, 95% CI 1.10–2.12), but the gain in discrimination was modest (absolute C-statistic increase 0.027–0.08) and no study performed decision curve analysis (DCA). suPAR did not distinguish focal segmental glomerulosclerosis (FSGS) from other glomerular diseases, and prognostic evidence in FSGS rested on a single moderate-quality study. In pediatric CKD and in metabolic cohorts, suPAR lost independent association after adjustment for baseline kidney function or inflammatory markers. Associations with cardiovascular outcomes were directionally consistent but observational and of low certainty. No study reported sex-stratified analyses.
Conclusions: Routine clinical measurement of suPAR is not currently supported; assay harmonization, sex-disaggregated analyses, prospective validation with decision curve analysis, and trials of suPAR-targeted therapy are needed first.
Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261320503 , identifier CRD420261320503.
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BibTeX
@article{wu2026soluble,
title = {{Soluble urokinase plasminogen activator receptor across the kidney–cardiometabolic continuum: a systematic review}},
author = {Qishun Wu and Zhiliang Yu and Xin Lin and Ling Yang and Zhangli Wu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1940345},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1940345/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Soluble urokinase plasminogen activator receptor across the kidney–cardiometabolic continuum: a systematic review
AU - Qishun Wu
AU - Zhiliang Yu
AU - Xin Lin
AU - Ling Yang
AU - Zhangli Wu
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1940345
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1940345/full
AB - Background: Soluble urokinase plasminogen activator receptor (suPAR), a circulating marker of innate immune activation, has been proposed as a risk biomarker in chronic kidney disease (CKD) and related cardiometabolic conditions, but its clinical utility remains uncertain. Methods: We performed a systematic review according to PRISMA 2020 and the Synthesis Without Meta-analysis (SWiM) guideline, searching PubMed, Embase, Web of Science, Scopus, the Cochrane Library, medRxiv, ClinicalTrials.gov, and WHO ICTRP from inception to May 15, 2026. Two reviewers independently screened records, extracted data, and assessed quality using the Newcastle-Ottawa Scale, the JBI checklist, RoB 2, and QUADAS-2; certainty of evidence was rated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: Twenty studies comprising 31,416 participants were included. In adults with preserved kidney function, elevated suPAR predicted incident CKD (adjusted odds ratio (OR) 3.13 for the highest versus lowest quartile, 95% confidence interval (CI) 2.11–4.65) and end-stage kidney disease (ESKD) (adjusted hazard ratio (HR) 1.53 for the highest versus lowest tertile, 95% CI 1.10–2.12), but the gain in discrimination was modest (absolute C-statistic increase 0.027–0.08) and no study performed decision curve analysis (DCA). suPAR did not distinguish focal segmental glomerulosclerosis (FSGS) from other glomerular diseases, and prognostic evidence in FSGS rested on a single moderate-quality study. In pediatric CKD and in metabolic cohorts, suPAR lost independent association after adjustment for baseline kidney function or inflammatory markers. Associations with cardiovascular outcomes were directionally consistent but observational and of low certainty. No study reported sex-stratified analyses. Conclusions: Routine clinical measurement of suPAR is not currently supported; assay harmonization, sex-disaggregated analyses, prospective validation with decision curve analysis, and trials of suPAR-targeted therapy are needed first. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261320503 , identifier CRD420261320503.
SN - 1664-3224
ER -