Longitudinal Analysis of sFas, sFasL, and sE-selectin as Predictive Biomarkers for Chronic Kidney Disease Progression in Children: PROGRESS Study

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Background: Chronic kidney disease (CKD) is a rare condition that causes significant health problems in children. Objectives: To evaluate changes in serum and urinary levels of soluble Fas (sFas), soluble Fas Ligand (sFasL), and soluble E-selectin (sE-selectin) over time in children with CKD and determine their potential as biomarkers for CKD progression. Methods: This longitudinal study was conducted as part of the PROGRESS study. A total of 117 patients with CKD and 56 healthy children were included. The CKD cohort underwent a 24-month prospective follow-up. Soluble Fas, sFasL, and sE-selectin levels were measured using the Luminex method at baseline, the 12th month, and the 24th month of the study. Results: At baseline, patients with CKD had significantly higher serum median levels of sFas, sFasL, and sE-selectin compared to the control group (8337 pg/mL vs. 3951 pg/mL, 68 pg/mL vs. 33 pg/mL, and 26460 pg/mL vs. 19801 pg/mL, respectively; P < 0.0001 for all). Additionally, the CKD group showed significantly higher urinary ratios of sFas/Cr, sFasL/Cr, and sE-selectin/Cr compared to the control group (P < 0.0001 for all). In the CKD group, median serum sFasL levels (68 pg/mL vs. 51 pg/mL) and urinary sFasL/Cr ratios (19 pg/mg vs. 14 pg/mg) significantly decreased at the 24th month compared to baseline (P < 0.0001 for both). Similarly, serum sE-selectin median levels and urinary sE-selectin/Cr ratios showed significant decreases over time (P = 0.003 and P < 0.0001, respectively). Baseline urinary sFas/Cr, sFasL/Cr, and sE-selectin/Cr ratios were highest in CKD stages 4 - 5 compared to stages 2, 3a, and 3b (P < 0.0001, P < 0.0001, and P = 0.007, respectively), while no significant differences were observed in baseline serum levels of sFas, sFasL, and sE-selectin across CKD stages (P > 0.05). Baseline serum sFasL median levels were lower (P = 0.038), while baseline serum sFas median levels were higher (P = 0.045) in patients with rapid CKD progression compared to those without rapid progression. Urinary sFas/Cr, sFasL/Cr, and sE-selectin/Cr ratios positively correlated with all urinary HSP/Cr ratios (P < 0.0001 for all). Conclusions: Our study highlights that CKD progression is a complex process involving sFas, sFasL, and sE-selectin; however, these biomarkers do not serve as predictors of CKD progression.

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