63 - Association of Syndecan-1 with Cardiovascular Disease Risk Factors in Proteinuric Glomerulopathies

Poster Number: 63
Publication Number: 63.2223

Background: Syndecan-1 (SDC-1), a cell surface proteoglycan, is a marker of endothelial glycocalyx injury that has been studied in recent years for its potential role as an independent cardiovascular disease (CVD) risk factor. However, the impact of SDC-1 on CVD risk factors in individuals with proteinuric glomerulopathies has not been well-studied.

Objective: To analyze the association of baseline SDC-1 with longitudinal blood pressure (BP) and lipid measurements in adults and children with proteinuric glomerulopathies.

Design/Methods: Analysis included adults and children enrolled in the multicenter Nephrotic Syndrome Study Network (NEPTUNE). The exposure of interest, serum SDC-1, was measured at the baseline visit using a commercial ELISA kit (Abcam, cat#ab46506, dilution 1:8). Casual BP was indexed (SBPi/DBPi) to the reference value used to define hypertensive BP (HTN) namely, BP ≥130/80 mmHg for participants ≥13 years and ≥95th percentile for those < 13 years. Dyslipidemia was defined as triglycerides ≥130 mg/dL, HDL cholesterol < 40 mg/dL or LDL cholesterol ≥130 mg/dL. Generalized estimating equation (GEE) regression analyses were used to determine the association of baseline log SDC-1 with BP and serum lipids over time. Models were adjusted for age, sex, disease cohort, follow-up time, log estimated glomerular filtration rate (eGFR), log urine protein/creatinine ratio (UPCR) and obesity.

Results: This study assessed 173 children (8.83 ± 5.03 years, 58.4% male, 39.9% white) with baseline median SDC-1 of 133.66 (IQR 74.83-192.49) ng/ml and 175 adults (44.42 ± 16.96 years, 60.6% male, 58.9% white) with median SDC-1 of 101.05 (IQR 56.70-145.40) ng/ml. Baseline characteristics also included median eGFR of 101.59 (IQR 69.92-133.26) ml/min/11.73m2 and UPCR of 4.72 (IQR –0.69-10.13) among children as well as median eGFR of 66.94 (IQR 44.40-89.49) ml/min/11.73m2 and UPCR of 2.91 (IQR 0.43-5.39) among adults. Among children, SBPi and DBPi were 0.88 and 0.87 respectively while among the adults, SBPi and DBPi were 0.77 and 0.91 respectively. In adjusted regression models, higher baseline SDC-1 was significantly associated with higher LDL cholesterol and higher total cholesterol (Table 1). SDC-1 was not significantly associated with BP (Figures 1 and 2).

Conclusion(s): Among participants enrolled in NEPTUNE, greater baseline serum SDC-1 was significantly associated with higher LDL cholesterol and higher total cholesterol. This association warrants further research to consider SDC-1 as a modifiable risk factor of CVD and a potential therapeutic target to reduce CVD in proteinuric glomerulopathies.