Adipokine, adropin and endothelin-1 levels in intrauterine growth restricted neonates and their mothers.

Intrauterine growth retardation/restriction (IUGR) is associated with fetal malnutrition. It has consequences for later life including increased incidence of obesity, diabetes mellitus, cardiovascular disease (CVD), and metabolic syndrome. Adipokines (adiponectin and leptin), adropin, and endothelin-1 are associated with obesity and metabolic syndrome regulation. Intrauterine changes in these mediators could affect programming of later adult obesity and metabolic syndrome. Our objectives were to compare the levels of these mediators in both cord and maternal blood between IUGR pregnancies and control, healthy pregnancies, and to study the correlation of adipokines with adropin and endothelin-1 in maternal and cord blood in IUGR pregnancies as well as in healthy control pregnancies. Maternal and cord blood samples were taken from 16 women with IUGR pregnancies and 16 women with healthy pregnancies. Serum levels of leptin, adiponectin, adropin, and endothelin-1 were measured by ELISA. Maternal blood adropin levels were significantly lower in the IUGR group than in the control group; the other mediators did not differ significantly. There was a positive correlation between maternal blood adropin and endothelin levels. (r=0.731, P=0.001) in the control but not the IUGR group. Cord blood adropin and adiponectin levels were significantly lower in the IUGR group compared with the control group, while leptin or endothelin-1 did not differ significantly. There was a negative correlation between adropin and leptin (r=-0.704, P=0.001) in the IUGR but not the control group cord blood. There were also positive correlations between endothelin and adropin for both groups (r=0.594, P=0.006; r=0.560, P=0.010, respectively); to the best of our knowledge, this is the first report of such a correlation. Differences in fetal expression of adropin and adiponectin in IUGR could influence programming of obesity, metabolic syndrome, diabetes, and CVD in later life.

Long-term results of children diagnosed with idiopathic nephrotic syndrome; single center experience.

AIM: The aim of this study was to determine the long-term results of children followed up with a diagnosis of nephrotic syndrome in a single center. MATERIALS AND METHOD: The medical data of 33 patients aged between 6 months and 10 years who were diagnosed with idiopathic nephrotic syndrome in our center between January 2000 and December 2012 and followed up for a period of 2-12 years were reviewed (Gulhane Military Medical Academy Ethics committee, 07.11.2012/10). RESULTS: The mean age of disease onset was 3.2±2.04 years (range: 0.5-10 years) and the mean follow-up period was 6±3.4 years (range: 2-12 years). Thirteen (39.4%) of the study group (or the patients) were female and 20 (60.6%) were male. Twenty seven (1.8%) of the patients were sensitive to steroid and 6 (18.1%) were resistant to steroid. Four (12.1%) of the steroid-resistant patients had steroid-dependent nephrotic syndrome, 5 (15.2%) had frequently relapsing nephrotic syndrome and 18 (54.5%) had rarely relapsing nephrotic syndrome. Histopathological diagnoses of six patients who underwent biopsy because of resistance to steroid were as follows: focal segmental glomerulosclerosis (n=3), C1q nephropathy (n=1), diffuse mesangial proliferation (n=1) and membraneous nephropathy (n=1). Fifteen (45.5%) patients entered into full remission and 2 (6%) patients developed chronic renal failure. Treatment complications including decreased bone mineral density in three patients (9%), short stature in 2 patients (6%) and cataract in 2 patients (6%) developed. CONCLUSIONS: Children with nephrotic syndrome carry a risk in terms of short stature, osteoporosis, cataract and renal failure in the long-term follow-up. It was observed that our rates of response to steroid were similar to the literature and the most common histopathological diagnosis was focal segmental glomerulosclerosis in our patients who underwent biopsy because of resistance to steroid. It was thought that multi-center studies should be conducted to demonstrate regional or national differences related with long-term results of childhood nephrotic syndrome.

Results of biofeedback treatment on reflux resolution rates in children with dysfunctional voiding and vesicoureteral reflux.

OBJECTIVES: It is well known that a relationship exists between vesicoureteral reflux (VUR) and dysfunctional voiding, and the spontaneous resolution rate in older children is lower than the rate in younger children. In this study, we analyzed our experience with biofeedback treatment in older children with confirmed voiding dysfunction and VUR and investigated the effect of this treatment on the reflux resolution rates in these children. METHODS: A total of 78 children, 5 to 14 years old (mean age 9), with voiding dysfunction and VUR detected by voiding cystourethrography were treated with biofeedback therapy. Voiding cystourethrography was performed 6 months after completion of the biofeedback program to determine the reflux status. The treatment results were also documented as subjective and objective improvements. RESULTS: The reflux in 98 units (20 bilateral) was grade 1 in 26, grade 2 in 32, grade 3 in 28, and grade 4 in 12. At 6 months of follow-up, VUR had resolved on voiding cystourethrography in 62 units (63%), the grade had improved in 28 units (29%), and the reflux had remained unchanged in 8 units (8%). Among the older children treated with biofeedback, we also observed improvements in nocturnal enuresis (82%), daytime wetting (70%), constipation (78%), frequency (76%), infrequency (64%), urgency (71%), staccato voiding (81%), flattened voiding (81%), bladder overactivity (82%), detrusor sphincter dyssynergia (77%), spinning top urethra (67%), and urinary tract infection (80%). CONCLUSIONS: Biofeedback therapy is applicable in older children with dysfunctional voiding and VUR and yields greater resolution rates than the historical resolution rates.

Minimal change nephropathy in a 7-year-old boy with Rosai-Dorfman disease.

Rosai-Dorfman (R-D) disease is a benign lympho-histiocytosis of the lymphoid system. Immune derangement due to cytokine over-expression (tumor necrosis factor (TNF), interleukin (IL)-1b and IL-6) has been considered the cause of R-D disease. We present a 7-year-old boy with R-D disease who developed minimal change nephropathy (MCN) during the progression of R-D disease. The patient was resistant to oral prednisolone; and the remission of both R-D disease and MCN was achieved with oral cyclophosphamide (2 mg/kg, 12 weeks). MCN, the most common cause of nephrotic syndrome in childhood, is generally accepted to emerge by way of cytokine derangement. Correlation between R-D disease activity and the development and remission of nephrotic syndrome in our case suggested that nephrotic syndrome had been induced through some R-D disease-related immune mechanisms.

Renin-angiotensin system gene polymorphisms: association with susceptibility to Henoch-Schonlein purpura and renal involvement.

The clinical course of Henoch-Schönlein Purpura (HSP) in children is variable, with some patients having a much more rapidly progressing course than others. We investigated whether polymorphisms of the renin-angiotensin system (RAS) genes are involved in HSP. Three RAS genotypes were examined in 114 children with HSP and in 164 healthy children: the angiotensin I converting enzyme (ACE) insertion/deletion polymorphism, the M235T mutation in the angiotensinogen gene (Agt), and the A1166C in the angiotensin II type I receptor (AT1R) gene. Significant differences were observed between HSP patients and control group in the frequency of ACE and Agt genotypes (p=0.004 and p=0.003, respectively). The TT genotype of Agt gene was associated with a 3.5-fold increased risk for Henoch-Schönlein nephritis (HSN) compared with the MM/MT genotype (odds ratio, 3.5; 95% confidence interval, 1.2-10.4). There was a trend to a higher prevalence of the TT genotype of the Agt gene among patients with nephrotic range proteinuria when compared to the patients with mild proteinuria, although the difference did not reach a statistical significance. The results of this study suggest that polymorphisms of ACE gene and Agt gene likely influence the risk of developing HSP. However, among the three genes of the RAS studies, only Agt gene was associated with the susceptibility to HSN. RAS gene polymorphisms studied are not associated with the presence of nephrotic range proteinuria. Additional studies are warranted to verify the correlation between RAS gene polymorphisms and susceptibility to HSP.

Plasma and urinary adrenomedullin levels in children with acute pyelonephritis.

AIM: Adrenomedullin (AM), a novel peptide recently isolated from pheochromocytoma, eliciting vasorelaxing activity, is the strongest among all known peptides. AM has been detected in the adrenal medulla, cardiac tissue, lung and kidney. Immunohistochemical studies have demonstrated the localization of AM in glomeruli, tubules and collecting cells of the kidney. Clinically, plasma and urinary AM levels are altered in patients with different renal disease. The present study aims to determine plasma and urinary AM levels in children with acute pyelonephritis (APN) and compare the results with a control group. MATERIALS AND METHODS: The study group was comprised of 19 patients with APN aged 11.6 +/- 3.7 months (range, 6-18 months) and the control group consisted of 16 cases aged 11.5 +/- 3.2 months (range, 7-16 months). Acute pyelonephritis was diagnosed by clinical, laboratory and imaging methods. Plasma and urinary AM levels were measured by high performance liquid chromotography (HPLC). RESULTS: The plasma AM levels were lower in APN patients (33.40 +/- 2.27 pmol/mL) than in the control group (43.76 +/- 4.27 pmol/mL) (P < 0.001), whereas the urinary AM levels were higher in APN patients (248.58 +/- 140.63 pmol/mg urinary creatinine) than in the control group (49.42 +/- 45.23 pmol/mg) (P < 0.001). Coefficients of correlation between urinary AM levels and C-reactive protein and white blood cells were statistically significant (r = 0.472, P = 0.041; r = 0.555, P = 0.014, respectively). CONCLUSION: Adrenomedullin, a smooth muscle relaxant peptide that is synthesized in urinary tract tissue might have a role in acute pyelonephritis. However, the importance of AM in the pathogenesis of acute pyelonephritis remains to be determined by further detailed studies.

Plasma and urinary adrenomedullin levels in children with renal parenchymal scar and vesicoureteral reflux.

Adrenomedullin (AM) is a strong vasodilator peptide with proven antimitogenic and antiproliferative effects in renal mesangial cells, as well as diuretic and natriuretic actions. Its gene expression is stimulated by endotoxins (lipopolysacharides) and cytokines. Consequently, its plasma and urinary levels are known to deviate from normal levels in many renal diseases. The purpose of this study is to determine plasma and urinary AM levels in children with renal parenchymal scar (RPS) and vesicoureteral reflux (VUR). The study was carried out on 74 children with recurrent urinary tract infections, arranged in groups: 25 patients with RPS with VUR (group I), 16 patients with RPS without VUR (group II), 12 patients with VUR without RPS (group III) and 21 healthy children as the control group. Plasma and urinary AM concentrations were both determined by high performance liquid chromotography (HPLC). Plasma AM was measured as picomoles per milliliter (pM/ml) and urinary AM as pM/mg urinary creatinine. In addition, serum creatinine, creatinine clearance and fractional sodium excretion (FE(Na)) were measured. All cases with RPS and VUR had normal blood pressure levels. The plasma AM levels were higher, although not significantly, in the control group (56.2+/-14.0 pM/ml) than in group I (50.6+/-4.2 pM/ml), group II (49.6+/-3.7 pM/ml) and group III (50.6+/-3.6 pM/ml) ( P =0.162). The urinary AM levels were higher in the control group (80.1+/-33.9 pM/mg) than in the three study groups (52+/-7.6 pM/mg, 58.6+/-7.5 pM/mg and 44.2+/-6.4 pM/mg; P =0.003, P =0.002 and P =0.002, respectively). There were no differences among the 4 groups (group I, group II, group III and the control group) in terms of FE(Na) and creatinine clearance ( P >0.05 and P >0.05, respectively). The finding that diminished urinary AM levels in patients with RPS and VUR implies that AM can be a prognostic factor in the long-term follow-up of cases with these diseases.