Adiponectin: an adipocyte-derived hormone, and its gene encoding in children with chronic kidney disease

BACKGROUND: The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with chronic kidney disease (CKD). Adiponectin (ADPN) is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. METHODS: On seventy eight advanced CKD (stages 4 and 5) pediatric patients undergoing maintenance hemodialysis( MHD) or conservative treatment (CT) the following parameters were studied: body mass index, left ventricular mass index(LVMI), serum adiponectin , cholesterol, HDL-cholesterol, high sensitivity C-reactive protein (hs CRP),interleukin 6(IL6) and single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene at positions 45, and 276. Seventy age-and gender-matched healthy subjects served as control subjects. RESULTS: Markedly (P = 0.01) elevated plasma adiponectin levels were observed in CKD patients, especially CT patients, compared to control subjects. The wild type of ADIPOQ 45T > G (T) allele is the main gene for patients and controls. MHD and CT patients had significantly higher frequency of the TT genotypes of +276G > T gene (P = 0.04) compared with control subjects. A significant positive correlation was observed between plasma adiponectin and IL6 level, whereas negative correlations were found between adiponectin level, cholesterol, HDL cholesterol and hs CRP. In a stepwise backward multiple regression model only IL6 (P = 0.001) was independently associated with plasma adiponectin levels. The adiponectin gene the 276 GT+TT genotypes were associated with a higher level of adiponectin . CONCLUSIONS: The present study demonstrated that ADPN is related to several metabolic and inflammatory CV risk factors in a manner consistent with the hypothesis that this protein might have a protective role against these factors. We observed an association between the +276G>T SNP in the adiponectin gene and CKD in children. Genetic variation of +276 gene seemed to have a positive impact on circulating adiponectin levels in CKD patients

Association of variable number tandem repeats polymorphism in the IL-4 gene with end-stage renal disease in children

Background: End stage renal disease (ESRD) is a common cause of morbidity and mortality among children. Interleukin 4 is a cytokine that might influence the progression of chronic kidney disease (CKD) to end stage renal disease. There are variable number of tandem repeats (VNTRs) in IL4 gene that could play major roles in genetic predisposition to some diseases. Aim of the study: The purpose of this study is to detect the association of allelic variant in intron 3 VNTR-IL4 gene with the end stage renal disease and if these variants could be considered as risk markers for this disease. Subjects and methods: The study was conducted on fifty-five children with CKD and fifty healthy children served as controls. All participants were genotyped for intron 3 VNTR by Polymerase Chain Reaction. Results: The frequency of intron 3 VNTR-IL4 P1P2 + P2P2 genotypes was significantly higher in ESRD-children than those with P1P1 genotype (88.7% vs. 15.4%, OR 43; 95% CI 13–134, P value < 0.001). Also, the frequency of P2 allele was significantly higher in ESRD-children compared with healthy controls (70.9% vs. 8%, OR 28; 95% CI 12–64, P value < 0.001). Furthermore, a significantly higher frequencies of P1P1 genotype and P1 allele among the control group were demonstrated (84.6% vs. 11.3%, P < 0.001 and 92% vs. 29.1%, P < 0.001, respectively). Conclusion: we concluded that the P2 allele is an allelic variant predisposing to ESRD in children with CKD and it could be considered a risk factor for the development of ESRD. Keywords: VNTR-IL4, ESRD, PCR, Children, Gene polymorphis

Adiponectin: an adipocyte-derived hormone, and its gene encoding in children with chronic kidney disease

Abstract Background The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with chronic kidney disease (CKD). Adiponectin (ADPN) is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. Methods On seventy eight advanced CKD (stages 4 and 5) pediatric patients undergoing maintenance hemodialysis( MHD) or conservative treatment (CT) the following parameters were studied: body mass index, left ventricular mass index(LVMI), serum adiponectin , cholesterol, HDL-cholesterol, high sensitivity C-reactive protein (hs CRP),interleukin 6(IL6) and single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene at positions 45, and 276. Seventy age-and gender-matched healthy subjects served as control subjects. Results Markedly (P = 0.01) elevated plasma adiponectin levels were observed in CKD patients, especially CT patients, compared to control subjects. The wild type of ADIPOQ 45T > G (T) allele is the main gene for patients and controls. MHD and CT patients had significantly higher frequency of the TT genotypes of +276G > T gene (P = 0.04) compared with control subjects. A significant positive correlation was observed between plasma adiponectin and IL6 level, whereas negative correlations were found between adiponectin level, cholesterol, HDL cholesterol and hs CRP. In a stepwise backward multiple regression model only IL6 (P = 0.001) was independently associated with plasma adiponectin levels. The adiponectin gene the 276 GT+TT genotypes were associated with a higher level of adiponectin . Conclusions The present study demonstrated that ADPN is related to several metabolic and inflammatory CV risk factors in a manner consistent with the hypothesis that this protein might have a protective role against these factors. We observed an association between the +276G>T SNP in the adiponectin gene and CKD in children. Genetic variation of +276 gene seemed to have a positive impact on circulating adiponectin levels in CKD patients.</p

Biomarkers of acute kidney injury in children with congenital heart disease after cardiopulmonary bypass

Background: Acute kidney injury (AKI) is a serious postoperative complication after cardiac surgery in children and is a major contributor to patient outcome. This study aims to identify the incidence of AKI in children undergoing cardiac surgery and the role of Interleukin 18 (IL-18) and Kidney Injury Molecule 1 (KIM-1) in diagnosis of AKI in comparison to creatinine. Methods: Forty-four children who underwent open heart surgery using cardiopulmonary bypass) for congenital heart disease were assessed for AKI diagnosis according the KDIGO criteria, urinary IL-18 and KIM-1 were determined by Enzyme Linked Immunosorbent Assay in addition to the assessment of length of stay in PICU and outcome and the effect of AKI on these parameters. Results: twenty three percent of the patient developed AKI, there were no statistical correlation between AKI and the factors (Age, gender, CBP and Risk adjustment for congenital heart surgery (RACHS-1) complexity score). Eight of our patients needed peritoneal dialysis (PD), seven of them developed AKI and the 8th patient didn’t develop due to the early initiation of PD. There was strong correlation between the development of AKI and the Length of stay in ICU

Genetic polymorphism of ACE and the angiotensin II type1 receptor genes in children with chronic kidney disease

Abstract Aim and Methods We investigated the association between polymorphisms of the angiotensin converting enzyme-1 (ACE-1) and angiotensin II type one receptor (AT1RA1166C) genes and the causation of renal disease in 76 advanced chronic kidney disease (CKD) pediatric patients undergoing maintenance hemodialysis (MHD) or conservative treatment (CT). Serum ACE activity and creatine kinase-MB fraction (CK-MB) were measured in all groups. Left ventricular mass index (LVMI) was calculated according to echocardiographic measurements. Seventy healthy controls were also genotyped. Results The differences of D allele and DI genotype of ACE were found significant between MHD group and the controls (p = 0.0001). ACE-activity and LVMI were higher in MHD, while CK-MB was higher in CT patients than in all other groups. The combined genotype DD v/s ID+II comparison validated that DD genotype was a high risk genotype for hypertension .~89% of the DD CKD patients were found hypertensive in comparison to ~ 61% of patients of non DD genotype(p = 0.02). The MHD group showed an increased frequency of the C allele and CC genotype of the AT1RA1166C polymorphism (P = 0.0001). On multiple linear regression analysis, C-allele was independently associated with hypertension (P = 0.04). Conclusion ACE DD and AT1R A/C genotypes implicated possible roles in the hypertensive state and in renal damage among children with ESRD. This result might be useful in planning therapeutic strategies for individual patients.</p