Serum Syndecan-1 is Associated With Kidney and Cardiovascular Outcomes in Idiopathic Nephrotic Syndrome

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.