<i>Background/Aims:</i> An oral adsorbent, AST-120, removes uremic toxins such as indoxyl sulfate, and delays the progression of renal failure. This study was designed to investigate the effects of AST-120 on the molecular basis of interstitial inflammation and fibrosis, using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus. <i>Methods:</i> Four weeks after unilateral nephrectomy, the uninephrectomized OLETF (1/2NxOLETF) rats were divided into two groups: AST-120-administered and control 1/2NxOLETF rats. After the administration of AST-120 for 48 weeks, we examined the effects of AST-120 on renal functional, pathological, and gene expressional changes. <i>Results:</i> The administration of AST-120 to the 1/2NxOLETF rats attenuated the progression of renal dysfunction, proteinuria, glomerular sclerosis, tubular injury, and interstitial inflammation and fibrosis. AST-120 significantly reduced renal expression of intercellular adhesion molecule (ICAM)-1, osteopontin, monocyte chemotactic protein (MCP)-1, and transforming growth factor (TGF)-β1, as well as clusterin. All the five molecules were expressed mainly in tubular cells. AST-120 also decreased serum and urinary levels of indoxyl sulfate and the overload of indoxyl sulfate in tubular cells. <i>Conclusion:</i> AST-120 ameliorates tubulointerstitial injury by reducing renal expression of ICAM-1, osteopontin, MCP-1, TGF-β1 and clusterin in 1/2NxOLETF rats.
Cardiovascular disease is a major cause of mortality in chronic kidney disease patients. Oxidative stress and nitric oxide (NO) deficiency play an important role in vascular endothelial cell dysfunction in chronic kidney disease. To determine if the uremic toxin indoxyl sulfate (IS) induces oxidative stress and inhibits NO production and cell viability in human umbilical vein endothelial cells (HUVEC).The production of reactive oxygen species (ROS), superoxide, NO and peroxynitrite was measured using a fluorescence microplate reader. The expression of NADPH oxidases (Nox4, Nox2) was analyzed by quantitative reverse transcription-polymerase chain reaction. Cell viability was examined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate assay.IS induced ROS generation in HUVEC. An inhibitor of NADPH oxidase showed an inhibitory effect on IS-induced ROS production. However, the inhibitors of xanthine oxidase, mitochondrial electron transport and NO synthase did not show any significant effect on IS-induced ROS production. Antioxidants such as vitamin E, N-acetyl-L-cysteine and vitamin C inhibited IS-induced ROS production. IS induced the expression of Nox4 mRNA and the production of superoxide and peroxynitrite in HUVEC. IS inhibited NO production in HUVEC. IS inhibited cell viability, and antioxidants preserve the inhibitory effect of IS on cell viability.IS inhibits NO production and cell viability by inducing ROS through induction of Nox4 in HUVEC.
Background. Patients with end-stage renal failure, whether on conservative or haemodialysis therapy, have a high incidence of DNA damage. It is not known if improved control of the uraemic state by daily haemodialysis (DHD) reduces DNA lesions.
Objective A long-surviving thanatophoric dysplasia type I patient to age of 6 years is presented. Results and Conclusions Molecular studies revealed a heterozygous point mutation, S249C in the fibroblast growth factor receptor 3 gene. Most of the clinical course was similar to previous reports, including hearing loss and acanthosis nigricans. Abnormal urinary excretion of dicarboxylic acids and 3-hydroxydicarboxylic acids was observed. We hypothesize that this was a consequence of the FGFR3 mutation.
