The sFas/sFasL ratio as a novel marker of inflammation in children with chronic kidney disease.
OBJECTIVE
Membrane Fas-FasL binding triggers apoptosis, enhanced in chronic kidney disease (CKD). However, the role of soluble forms, sFas and sFasL, remains unclear. Matrix metalloproteinases (MMPs) are known converters of sFasL from the membrane-bound form, but there are no data on relations between sFas/sFasL, MMPs, their tissue inhibitors (TIMPs) or inflammatory/endothelial factors in CKD patients. We aimed to evaluate correlations between sFas, sFasL, MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2, and the role of sFas/sFasL as markers of inflammation and endothelial dysfunction.


METHODS
Serum concentrations of sFas, sFasL, MMPs, TIMPs, hsCRP, IL-4 and sE-selectin were assessed by ELISA in 65 CKD children and in 30 controls.


RESULTS
sFas, sFasL, sFas/sFasL ratio, MMPs, TIMPs, sE-selectin and IL-4 levels were significantly enhanced in CKD patients vs. controls. sFas/sFasL ratio correlated with inflammatory/endothelial markers. sE-selectin was the best predictor of sFas and sFas/sFasL ratio. MMP-9, TIMP-1 and IL-4 predicted most accurately the sFasL concentrations.


CONCLUSIONS
CKD children present with progressive sFas/sFasL dysfunction. Relations between sFas/sFasL, MMPs and TIMPs indicate the potential role of metalloproteinases in the sFas/sFasL regulation. Correlations with hsCRP, sE-selectin and IL-4 suggest that sFas/sFasL ratio may become a new marker of inflammation and endothelial dysfunction in children with CKD.
Department of Pediatric Nephrology, Wrocław Medical University, Borowska 213, 50–556 Wrocław, Poland.
Kinga
K
Musiał
Danuta
D
Zwolińska
D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000378:metabolism; D008297:Male; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000378:metabolism; D012189:Retrospective Studies; D019014:fas Receptor / Q000097:blood* / Q000378:metabolism
D015415:Biomarkers; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor