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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Elsevier
2025-08-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024925002803 |
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| author | Colin Bauer Arshia Anand Christine Sethna Jonathan Troost Tarak Srivastava Imtiazul Islam Audrey Fetsko Julie A. Dougherty William E. Smoyer Richard J. Johnson Gabriel Cara-Fuentes |
| author_facet | Colin Bauer Arshia Anand Christine Sethna Jonathan Troost Tarak Srivastava Imtiazul Islam Audrey Fetsko Julie A. Dougherty William E. Smoyer Richard J. Johnson Gabriel Cara-Fuentes |
| author_sort | Colin Bauer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dc6e37ab1f2043aba1488338760b8137 |
| institution | DOAJ |
| issn | 2468-0249 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-dc6e37ab1f2043aba1488338760b81372025-08-20T03:16:00ZengElsevierKidney International Reports2468-02492025-08-011082732274010.1016/j.ekir.2025.04.055Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic SyndromeColin Bauer0Arshia Anand1Christine Sethna2Jonathan Troost3Tarak Srivastava4Imtiazul Islam5Audrey Fetsko6Julie A. Dougherty7William E. Smoyer8Richard J. Johnson9Gabriel Cara-Fuentes10Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Division of Pediatric Nephrology, Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USADivision of Pediatric Nephrology, Cohen Children's Medical Center, New Hyde Park, New York, USADivision of Pediatric Nephrology, Cohen Children's Medical Center, New Hyde Park, New York, USAMichigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, Michigan, USAPediatric Nephrology, Children’s Mercy Hospital, Kansas City, Missouri, USADivision of Pediatric Nephrology, Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USADivision of Pediatric Nephrology, Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USADivision of Pediatric Nephrology, Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children's, Hospital, Columbus, Ohio, USADivision of Pediatric Nephrology, Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children's, Hospital, Columbus, Ohio, USADepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USADepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Division of Pediatric Nephrology, Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Correspondence: Gabriel Cara-Fuentes, 700 Children’s Dr, Columbus, Ohio 43250, USA.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.http://www.sciencedirect.com/science/article/pii/S2468024925002803biomarkercardiovascular outcomesendothelial glycocalyxidiopathic nephrotic syndromeNEPTUNEsyndecan-1 |
| spellingShingle | Colin Bauer Arshia Anand Christine Sethna Jonathan Troost Tarak Srivastava Imtiazul Islam Audrey Fetsko Julie A. Dougherty William E. Smoyer Richard J. Johnson Gabriel Cara-Fuentes Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic Syndrome Kidney International Reports biomarker cardiovascular outcomes endothelial glycocalyx idiopathic nephrotic syndrome NEPTUNE syndecan-1 |
| title | Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic Syndrome |
| title_full | Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic Syndrome |
| title_fullStr | Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic Syndrome |
| title_full_unstemmed | Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic Syndrome |
| title_short | Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic Syndrome |
| title_sort | serum syndecan 1 is associated with kidney and cardiovascular outcomes in idiopathic nephrotic syndrome |
| topic | biomarker cardiovascular outcomes endothelial glycocalyx idiopathic nephrotic syndrome NEPTUNE syndecan-1 |
| url | http://www.sciencedirect.com/science/article/pii/S2468024925002803 |
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