Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic Syndrome
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. Meth...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
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| Series: | Kidney International Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024925002803 |
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| Summary: | 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. |
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| ISSN: | 2468-0249 |