A pilot study on gene expression of endoplasmic reticulum unfolded protein response in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem due to its increasing prevalence worldwide. Endoplasmic reticulum (ER) stress has been shown to play a role in the pathogenesis of various renal diseases in humans. It leads to the activation of the unfolded protein response (UPR) which triggers three known trans membrane sensors in the ER: activating transcription factor 6 (ATF6), inositol-requiring enzyme I (IRE1), and PKR (double-stranded RNA-dependent protein kinase)-like ER protein kinase (PERK). The activation of these signal transduction pathways can result in cell death, inflammation, and fibrosis in the context of CKD. OBJECTIVES: The aim of this study was to detect the level of gene expression of activating transcription factor 6 (ATF6), inositol-requiring enzyme I (IRE1), and PKR (double-stranded RNA-dependent protein kinase)-like ER protein kinase (PERK) in chronic kidney disease patients. SUBJECTS AND METHODS: This study was carried out on eighty subjects, 50 patients with CKD (25 with hypertension and 25 without hypertension) and 30 healthy subjects served as controls. All studied subjects underwent laboratory investigations, including CBC, Serum Lipid profile: Total cholesterol, Triglycerides, HDL-cholesterol and LDL-cholesterol, liver and kidney functions, fasting and 2 h postprandial blood glucose and HbA1C, serum level of IL6 and gene expression of ATF6, IRE1 and PERK using real time PCR technique. RESULTS: There was a significant increase in relative quantitation (RQ) of gene expression of IRE1, ATF6 and PERK in chronic kidney patient groups with hypertension and without hypertension compared to control group. Also, there was a significant positive correlation of PERK and ATF6 gene expressions and a significant negative correlation of PERK gene expressions and GFR in groups I&II. CONCLUSION: Endoplasmic reticulum (ER) stress occurs in CKD with activation of gene expression of three trans-membrane sensors in the ER: activating transcription factor 6 (ATF6), inositol-requiring enzyme I (IRE1), and PKR (double-stranded RNA-dependent protein kinase)-like ER protein kinase (PERK).

Relation of neuropeptide Y gene expression and genotyping with hypertension in chronic kidney disease.

OBJECTIVES: The prognosis of high-risk patients might be greatly ameliorated using genetic predisposition risk factors. Sympathetic activity and innate immunity related to neuropeptide Y function may be related to dyslipidemia and atherosclerosis. The aim of this study is to detect the correlation between Neuropeptide Y (NPY) SNP rs16147 and its gene expression in chronic kidney disease with and without hypertension. METHODS: This study carried out on 150 subjects who were divided into 3 main groups group (I) 50 CKD patients with hypertension, group (II) 50 CKD patients without hypertension and group (III) 50 healthy individuals. Carotid intima media thickness (CIMT) was measured by Ultrasound. Kidney function test and lipid profile were performed. Genotyping and gene expression of neuropeptide Y (NPY) were performed using real time PCR. RESULTS: There was a significant increase in number and percentage of CC genotype and C allele of NPY SNP distribution in CKD patients with and without hypertension when compared to controls. A significant association was found between CC genotype and C allele and the risk of CKD with hypertension with odd ratio 3.26 and 1.77, respectively. There is a significant positive correlation between NPY gene expression level and CIMT among chronic kidney disease patients with highest level of TC, LDLc and CIMT among CC genotype of NPY gene. CONCLUSION: A significant association was found between CC genotype and C allele of NPY at rs16147 with increase NPY gene expression and risk of developing hypertension in CKD.