Marcin Tkaczyk1,2, Monika Miklaszewska3, Jolanta Lukamowicz4, Wojciech Fendler5. 1. Division of Nephrology, Polish Mother's Memorial Hospital Research Institute, 281/289 Rzgowska St. 93-338, Łódź, Poland. mtkaczyk@uni.lodz.pl. 2. Medical University of Łódź, al. Kościuszki 4, Łódź, Poland. mtkaczyk@uni.lodz.pl. 3. Department of Pediatric Nephrology, Collegium Medicum of Jagiellonian University, Wielicka 265 30-663, Kraków, Poland. 4. Center of Medical Diagnostics, Polish Mother's Memorial Hospital Research Institute of Łódź, 281/289 Rzgowska st. 93-338, Łódź, Poland. 5. Medical University of Łódź, al. Kościuszki 4, Łódź, Poland.
Abstract
BACKGROUND: The role of idiopathic nephrotic syndrome (INS) in the pathogenesis of atherosclerosis in childhood has not been clearly elucidated. However, antioxidative defense in INS is thought to be imbalanced. This study aimed to assess the changes of plasma concentration of selected aminothiols in the blood of children with INS at various stages of the disease. METHODS: This cross-sectional study was conducted in 125 children aged 2-18 years. The children were divided into 4 groups: group A, early relapse (n=37); group B, early remission for 4-6 weeks from the onset (n=37); group C, late steroid-free remission (n=31); and group D, long-term remission for 2-5 years (n=20). Control group (E) consisted of 30 age- and gender-matched healthy children. The study protocol comprised an analysis of plasma concentrations of glutathione, homocysteine, cysteine and cysteinylglycine by high-performance liquid chromatography. Fractions of protein-bound and free aminothiols were measured. Endothelial injury was assessed by thrombomodulin, PAI-1 concentration, and von Willebrand factor activity. RESULTS: The children with INS had unbalanced aminothiol metabolism only in relapse and early remission, that shifted towards increased oxidative processes. Administration of cyclosporine A caused a significant increase in homocysteine and cysteine concentration. Changes in aminothiol metabolism were significantly related to endothelial injury. CONCLUSIONS: The findings of this study may be helpful in elucidating the pathogenesis of premature atherosclerosis in patients with INS refractory to the treatment or in the case of frequent relapse.
BACKGROUND: The role of idiopathic nephrotic syndrome (INS) in the pathogenesis of atherosclerosis in childhood has not been clearly elucidated. However, antioxidative defense in INS is thought to be imbalanced. This study aimed to assess the changes of plasma concentration of selected aminothiols in the blood of children with INS at various stages of the disease. METHODS: This cross-sectional study was conducted in 125 children aged 2-18 years. The children were divided into 4 groups: group A, early relapse (n=37); group B, early remission for 4-6 weeks from the onset (n=37); group C, late steroid-free remission (n=31); and group D, long-term remission for 2-5 years (n=20). Control group (E) consisted of 30 age- and gender-matched healthy children. The study protocol comprised an analysis of plasma concentrations of glutathione, homocysteine, cysteine and cysteinylglycine by high-performance liquid chromatography. Fractions of protein-bound and free aminothiols were measured. Endothelial injury was assessed by thrombomodulin, PAI-1 concentration, and von Willebrand factor activity. RESULTS: The children with INS had unbalanced aminothiol metabolism only in relapse and early remission, that shifted towards increased oxidative processes. Administration of cyclosporine A caused a significant increase in homocysteine and cysteine concentration. Changes in aminothiol metabolism were significantly related to endothelial injury. CONCLUSIONS: The findings of this study may be helpful in elucidating the pathogenesis of premature atherosclerosis in patients with INS refractory to the treatment or in the case of frequent relapse.
Authors: Om P Mishra; Aditya K Gupta; Rajniti Prasad; Ziledar Ali; Ram S Upadhyay; Surendra P Mishra; Narendra K Tiwary; Franz S Schaefer Journal: Pediatr Nephrol Date: 2010-11-21 Impact factor: 3.714