Increased plasma levels of Urotensin-II in preeclampsia–eclampsia: a new mediator in pathogenesis?

OBJECTIVE: To assess the possible role of human Urotensin-II (hU-II), a vasoactive peptide, in the pathophysiology of preeclampsia-eclampsia prospectively. STUDY DESIGN: Sixty subjects, 30 with a diagnosis of preeclampsia-eclampsia (group I) and 30 control subjects (group II), who had been admitted between January, 2002 and December, 2002, were taken into the study. Patients in group I had an increase in blood pressure after 28th week of gestation, without any history of hypertensive disease and/or preeclampsia or eclampsia. hU-II levels were assessed using a radioimmunoassay method. RESULTS: No statistically significant difference in terms of age, gestational age, gravidity, abortion and parity was detected among groups (P > 0.05). Plasma hU-II levels in the preeclampsia-eclampsia and control groups were 10.11 +/- 5.94 pg/mL and 3.93 +/- 1.73 pg/mL, respectively. Difference between plasma hU-II levels of the two groups was found to be statistically significant (P < 0.00001). Also there was correlation between hU-II levels and mean arterial pressures in both groups (r = 0.73, P < 0.0001 and r = 0.72, P < 0.0001 for groups I and II, respectively). CONCLUSION: Results of our study strongly suggest an important role for hU-II in the pathophysiology of preeclampsia-eclampsia. Further studies concerning placenta and cord blood samples will more clearly elucidate the role of Urotensin-II in the pathogenesis of preeclampsia-eclampsia, and its feto-maternal effects.     

Carotid artery thickness in children and young adults with end stage renal disease

Atherosclerosis is a major cause of morbidity and mortality for ESRD patients and we have little knowledge about the presence and risk factors of atherosclerosis in children with CRF. The measurement of carotid artery intima-media thickness (cIMT) using high-resolution ultrasonography is suggested as an excellent marker of subclinical atherosclerosis. In this study, we aimed to investigate the presence of atherosclerosis and to determine the relationship between atherosclerosis and some risk factors in children and young adults with ESRD. Thirty-four patients with ESRD and 20 controls were included in this study. The measurement of cIMT was performed by using a linear B-mode 7.5-MHz ultrasound transducer. We determined anemia, abnormal calcium/phosphate metabolism, hyperhomocysteinemia, hypertriglyceridemia and increased lipoprotein (a) levels in the ESRD group. The cIMT in the ESRD group was higher than in the control group (P<0.05). SBP, DBP, MAP, LVMI and LVH prevalence were statistically higher in the ESRD group (P<0.05). There were significant positive correlations between cIMT and LVMI, MBP, whereas a significant negative correlation was determined between cIMT and PTH in the ESRD group (P<0.05). When a multiple linear regression analysis was performed with cIMT as a dependent variable and LVMI, MBP, PTH, as independent variables, a significant positive correlation was determined between cIMT and LVMI (P<0.05). In conclusion, we think that arteriopathy occurs in children with ESRD. Left ventricular hypertrophy and hypertension may associate with vascular changes in children and young adults with ESRD. Further investigations are necessary to explain association of LVMI index with cIMT.     

NPHS2 (podicin) mutations in Turkish children with idiopathic nephrotic syndrome

The podocin (NPHS2) gene encodes podocin protein, which has an important role in glomerular ultrafiltration and controlling slit membrane permeability. The detection of an NPHS2 mutation affects the treatment plan for children with nephritic syndrome (NS). The frequency and spectrum of podocin mutations in the Turkish population have remained largely unknown. The aim of this study was to screen for podocin mutations in Turkish patients with steroid-resistant NS (SRNS) and to compare it with other published series. There were 295 children with SRNS, originating from Turkey, included in this study. Forty-one patients (13.8%) had familial NS and 254 patients (86.2%) had sporadic NS. Mutation analysis was performed in all eight exons of the NPHS2 gene with the direct DNA sequencing method. There were 53 different pathogenetic NPHS2 mutations detected, including 37 novel mutations. The mutation detection rate was 24.7% for all patients, 29.2% for familial, and 24% for sporadic SRNS. The most common mutated exon was exon 5 (52 allele). The presence of mutations in exon 4 was found to increase the risk of end-stage renal disease (ESRD). Among patients with mutations, the rates of renal failure and/or ESRD (26%) were significantly higher than in those without mutations (12.6%). The mean time of progression to renal failure and ESRD in patients with mutations (1.8 ± 2.5 years) was significantly shorter than in patients without mutations (3.7 ± 4.0 years). Additionally, in patients with heterozygote mutations, fewer cases (13.6%) progressed to renal failure and/or ESRD than in with patients who had homozygote/compound heterozygote mutations (31.3%). In conclusion, podocin mutations are responsible for some of both familial and sporadic SRNS cases in Turkey. The mutations in this gene should be searched for in every child after presentation with the first episode of NS.     

Chemopreventive efficacies of rosiglitazone, fenretinide and their combination against rat mammary carcinogenesis

Introduction  

Peroxisome proliferator-activated receptor gamma (PPAR-γ) and retinoic acid receptors (RAR/RXR) belong to the nuclear steroid receptor family. In vitro studies have suggested that PPAR-γ ligands are highly effective in preventing mammary tumours and these effects are enhanced by some retinoids. However, in vivo anti-initiator and anti-promoter efficacies of this combination are not clear.     

Membranous nephropathy presenting with nephrotic syndrome in a child with thalassemia major

Few data on the renal effects of thalassemia syndrome are available in the literature. Recent clinical studies identified proximal tubular damage and glomerular filtration abnormalities in thalassemia. Iron‐chelating agents might be nephrotoxic as well, but proven glomerular injury, either due to anemia or chelating therapy, has not previously been demonstrated in thalassemia patients. Here, we report the first thalassemia patient presenting with nephrotic syndrome to be diagnosed with membranous nephropathy in the literature.     

The Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) Study: Objectives,Design, and Methodology

Background and objectives: Children and adolescents with chronic kidney disease (CKD) are at high risk for cardiovascular morbidity and mortality. A systemic arteriopathy and cardiomyopathy has been characterized in pediatric dialysis patients by the presence of morphologic and functional abnormalities.Design, setting, participants, & measurements: The Cardiovascular Comorbidity in Children with CKD (4C) Study is a multicenter, prospective, observational study aiming to recruit more than 600 children, aged 6 to 17 years, with initial GFR of 10 to 45 ml/min per 1.73 m². The prevalence, degree, and progression of cardiovascular comorbidity as well as its association with CKD progression will be explored through longitudinal follow-up. The morphology and function of the heart and large arteries will be monitored by sensitive noninvasive methods and compared with aged-matched healthy controls. Multiple clinical, anthropometric, biochemical, and pharmacologic risk factors will be monitored prospectively and related to the cardiovascular status. A whole-genome association study will be performed to identify common genetic variants associated with progression of cardiovascular alterations and/or renal failure. Monitoring will be continued as patients reach end-stage renal disease and undergo different renal replacement therapies.Results: While cardiovascular morbidity in adults is related to older age and additional risk factor load (e.g., diabetes), the role of CKD-specific factors in the initiation and progression of cardiac and vascular disease are likely to be characterized with greater sensitivity in the pediatric age group.Conclusions: The 4C study is expected to provide innovative insight into cardiovascular and renal disease progression in CKD.Children and adolescents with chronic kidney disease (CKD) are at high risk for cardiovascular events (1). In young adults with end-stage renal disease, cardiovascular mortality is increased 500- to 1000-fold compared with the general population (2).Young CKD patients usually do not present with clinical symptoms of cardiovascular disease (CVD). Ischemic heart disease and myocardial infarction are very rare in childhood. However, even children may present with subclinical CVD, and significant structural and functional changes of the heart and the large arteries can be detected by sensitive methods (3,4).Recently, noninvasive measurements of vascular morphology and function such as carotid artery intima-media thickness (cIMT), pulse wave velocity (PWV), and the pulse wave augmentation index (AI) have been established as valid surrogate markers of arteriopathy in adult CKD patients (5). Similar to echocardiographic findings (6), these surrogate markers are highly predictive for future cardiovascular events.The pediatric population appears uniquely suited to study the effects of CKD on the cardiovascular system due to the virtual absence of vascular morbidity related to aging, diabetes, and smoking. However, the factors underlying early cardiovascular morbidity in CKD and their relative contribution are poorly understood. Moreover, the natural evolution of cardiovascular lesions and their relationship to kidney disease progression are largely unknown due a lack of prospective observational studies in a sufficiently large cohort of pediatric CKD patients.To improve our understanding of the causes and consequences of cardiovascular comorbidity in children with CKD, a consortium of pediatric nephrologists in Europe has joined to perform a long-term prospective observational study monitoring the cardiovascular health of children as they advance through successive stages of CKD. The Cardiovascular Comorbidity in Children with CKD (4C) Study will follow up to 625 patients in more than 50 pediatric nephrology units in 14 European countries (http://www.4c-study.org).     

Endothelial nitric oxide synthase gene intron 4 a/b VNTR polymorphism in children with APSGN

The role of endothelial nitric oxide synthase gene intron 4 a/b (eNOS4a/b) variable number of tandem repeats (VNTR) polymorphism in various renal diseases was investigated. We investigated whether the eNOS4a/b VNTR polymorphism is associated with susceptibility to acute poststreptococcal glomerulonephritis (APSGN) and its clinical features. Endothelial NOS4a/b VNTR polymorphism is determined by the polymerase chain reaction in 60 children with APSGN, and 66 healthy controls. The genotype distribution of eNOS4 does not differ between the patients and the controls (X²=5.1, p=0.079). However, the frequency of eNOS4a (eNOS4a/a and eNOS4a/b) genotype is higher in the patients than in the controls (X²=4.5, p=0.046). In the APSGN group we performed renal biopsy on eight patients because of nephrotic syndrome accompanies acute nephritic syndrome or glomerular filtration rate (GFR) is lower than 50% of normal, and found that to carry a/a and a/b genotypes were a significant risk factor for this type presentation (OR=17.3, 95% CI:1.95-152.67, p=0.03). Mean serum creatinine values are found statistically significantly higher in a/a and a/b genotypes when compared with b/b genotypes (p=0.022). Children carrying the “aa” and “ab” genotype or “a” allele of eNOS4 have a greater tendency to develop and clinical presentation of APSGN.     

Mycophenolate mofetil in children with multidrug-resistant nephrotic syndrome

AIM: The aim of the present study is to report our clinical experiences with MMF in problematic children with chronic glomerulonephritis resistant to corticosteroids and/or other immunosuppressive drugs. PATIENTS AND METHODS: Ten patients with chronic glomerulonephritis resistant to treatment with corticosteroids and other immunosuppressive drugs were treated with mycophenolate mofetil (MMF). Causes of chronic glomerulonephritis were mesangial proliferative glomerulonephritis (4), membranoproliferative glomerulonephritis (3), chronic sclerosing glomerulonephritis (1), focal segmental glomerulosclerosis (1), diffuse endo- and extracapillary proliferative glomerulonephritis (1). MMF 15 mg/kg was used in combination with low-dose corticosteroids and angiotensin-converting enzyme inhibitors. RESULTS: During 24 weeks of MMF therapy, no significant changes were detected in mean serum creatinine, albumin and proteinuria. Severe leukopenia was seen in 1 patient. Additional adverse effects, including nausea and diarrhea, were observed in another patient when the dosage was increased to 20 mg/kg per day. During MMF treatment proteinuria decreased slightly without remission in 6 of 10 patients. CONCLUSION: Further data and clinical trials are needed to evaluate the possible role of MMF in the treatment of chronic glomerulonephritis of similar etiologies in pediatric patients.     

Effects of sibutramine in non-dieting obese women

The aim of this study was to evaluate the effects of sibutramine on plasma leptin levels, body weight and glucose metabolism in non-dieting women. Fourteen healthy, non-diabetic, obese women were studied before treatment, after 1 week of placebo administration, and after a 2-week course of sibutramine (10 mg/day). At each of these stages, we assessed body composition, measured the levels of plasma leptin, C-peptide and various biochemical parameters, and also recorded plasma insulin and glucose levels during oral glucose tolerance tests. After 1 week of placebo treatment, there were no significant changes in any of the parameters. However, two weeks of 10 mg/day sibutramine dropped plasma leptin levels from a mean (+/-SE) of 48.84+/-4.54 to 42.84+/-4.74 ng/ml (p<0.04), reduced BMI from 39.36+/-2.01 to 38.57+/-1.93 kg/m2 (p<0.002), and decreased insulin resistance (IR, as measured using the homeostasis model assessment of insulin resistance) from 5.59+/-0.85 to 3.66+/-0.43 (p<0.02). There was no correlation between the reduction in leptin concentration and the decrease in BMI, fat mass, percent body fat, IR, C-peptide, or the area under curve for glucose or insulin. There was also no correlation between the decrease in leptin levels and the increases that occurred in the insulin sensitivity index or the hepatic sensitivity index. The results showed that treatment with 10 mg/day sibutramine significantly reduces BMI, IR and leptin levels in non-dieting obese women.     

Association between postprandial hyperinsulinemia and coronary artery disease among non-diabetic women: a case control study

BACKGROUND: We planned a case-control study to assess the relation of fasting glucose, fasting insulin, postprandial glucose and postprandial insulin levels with coronary artery disease in nondiabetic women. METHODS: Among 968 consecutive nondiabetic women screened, 104 with coronary artery disease (mean age 60, 4+/-9) made up the study cohort (group I). One-hundred and four age-matched, nondiabetic women without coronary artery disease who had a similar lipid and blood pressure profile (group II), and 52 healthy, age-matched women served as controls (group III, real control group). Demographics, waist circumference, lipids, fasting glucose postprandial glucose, fasting and postprandial insulin levels were compared among the groups. A separate subgroup analysis were performed in patients with metabolic syndrome. RESULTS: No differences were identified in terms of prevalences of risk factors between group I and group II. Women with coronary artery disease had higher postprandial insulin level than the women in group II and group III. In reverse stepwise logistic regression analysis postprandial hyperinsulinemia was found to be the single independent determinant for coronary artery disease for the entire study group as well as for women with metabolic syndrome. CONCLUSION: Our data demonstrate that postprandial hyperinsulinemia is independently associated with coronary artery disease, irrespective of fasting glucose, postprandial glucose, and fasting insulin levels in nondiabetic women with clusterings of factors of metabolic syndrome.