Document Type
Article
Publication Date
8-2025
Identifier
DOI: 10.1016/j.ekir.2025.04.055; PMCID: PMC12347788
Abstract
INTRODUCTION: Idiopathic nephrotic syndrome (INS) is associated with important kidney and cardiovascular morbidities. We tested the hypothesis that serum syndecan-1, a marker of endothelial glycocalyx injury, can help identify patients at risk for unfavorable kidney and cardiovascular outcomes.
METHODS: We included 348 children and adults with INS (n = 35 unbiopsied, n = 141 minimal change disease [MCD] and n = 172 focal segmental glomerulosclerosis [FSGS]) from the Nephrotic Syndrome Study Network (NEPTUNE) cohort and 34 healthy participants (n = 22 adults, n = 12 children). We measured baseline serum syndecan-1 levels using an enzyme-linked immunosorbent assay and evaluated their relationship with kidney and cardiovascular outcomes. We performed in vitro studies to test whether INS sera and different therapeutics may alter syndecan-1 expression in human glomerular endothelial cells (GEnC).
RESULTS: Serum syndecan-1 was higher in patients with INS than in controls and was high in approximately one-third of patients without proteinuria or with subnephrotic proteinuria. Patients receiving steroids, regardless of disease activity, showed higher syndecan-1 than those off immunosuppression. Syndecan-1 was higher in proteinuric patients with MCD than in FSGS. At the time of serum collection, syndecan-1 modestly correlated with proteinuria but not with kidney function. In longitudinal analyses, serum syndecan-1 was associated with the composite of 40% decline in kidney function or kidney failure and with dyslipidemia. Compared with controls, INS sera in relapse increased syndecan-1 expression in cultured GEnC, and this was partially or fully mitigated when dexamethasone or a metalloprotease inhibitor were added, respectively, to culture media.
CONCLUSION: Baseline serum syndecan-1 is associated with unfavorable kidney outcomes and cardiovascular risk factors in INS.
Journal Title
Kidney Int Rep
Volume
10
Issue
8
First Page
2732
Last Page
2740
PubMed ID
40814613
Keywords
NEPTUNE; biomarker; cardiovascular outcomes; endothelial glycocalyx; idiopathic nephrotic syndrome; syndecan-1
Recommended Citation
Bauer C, Anand A, Sethna C, et al. Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic Syndrome. Kidney Int Rep. 2025;10(8):2732-2740. Published 2025 May 6. doi:10.1016/j.ekir.2025.04.055
Comments
This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.
Publisher's Link: https://www.kireports.org/article/S2468-0249(25)00280-3/fulltext