The sFas/sFasL ratio as a novel marker of inflammation in children with chronic kidney disease

Objectives: 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. (C) 2012 Elsevier B.V. All rights reserved.