Bahar Büyükkaragöz

Hypertension in Pediatric Patients With Renal Scarring in Association With Vesicoureteral Reflux

OBJECTIVE To examine the reflux nephropathy rate and severity as well as the hypertension rate in pediatric patients with vesicoureteral reflux (VUR). METHODS The study included 240 patients with VUR. Renal scarring (RS) was demonstrated by renal parenchymal examination using technetium-99m-labeled dimercaptosuccinic acid (99mTc-DMSA) scintigraphy. Office measurements of arterial blood pressure and ambulatory blood pressure monitoring (ABPM) of VUR patients were done during the follow-up period. RESULTS Follow-up was a mean duration of 24 months. Rates of RS and hypertension increased parallel to increases in the degree of VUR. A gradual elevation in hypertension rates was evident during the follow-up period. All patients with hypertension had RS. Severe RS in 56 patients was associated with increasing blood pressure readings by 24-hour ABPM or office measurements in 19 patients (33.9%). ABPM measurements enabled us to detect additional patients compared with office measurements alone. CONCLUSION Hypertension is a serious complication in children with reflux nephropathy and is associated with the severity of RS and VUR grade. ABPM seems to be superior over office measurements of blood pressure in identifying patients with hypertension.

MICRONUCLEUS FREQUENCIES IN PERIPHERAL BLOOD LYMPHOCYTES OF CHILDREN WITH CHRONIC KIDNEY DISEASE

One of the crucial adverse effects of chronic kidney disease (CKD) and its treatment is an elevated cancer risk. There are no data on cytogenetic effects in children with CKD or children undergoing dialysis or those who have received a transplant. In this study, cytogenetic effects in children with CKD in pre-dialysis (PreD) stage, on regular haemodialysis (HD) and transplanted (Tx) compared with a control group of healthy children has been investigated using the cytokinesis-blocked micronucleus (CBMN) assay and fluorescence in situ hybridisation (FISH) combined with CBMN (CBMN-FISH) in peripheral blood lymphocytes. The results revealed a significant increase (P < 0.001) in micronucleus (MN) frequencies [mean ± SD (n)] in the PreD, HD and Tx groups versus the control group [CBMN assay; 9.19 ± 2.61 (16), 9.07 ± 4.86 (15), 6.12 ± 5.33 (17) versus 1.60 ± 0.99 (20), respectively]. Moreover, centromere negative micronucleus (C- MN) and centromere positive micronucleus (C+ MN) frequencies were significantly higher in each subgroup children (PreD, HD and Tx) than in the control group (P < 0.01) although children in Tx group had lower C- MN frequencies than PreD and lower C+ MN frequencies than PreD and HD groups (P < 0.05). Additionally, MN frequencies in mononuclear cells, nucleoplasmic bridges and nuclear buds in binucleated cells were increased in children with CKD (P < 0.001, P < 0.001, P > 0.05, respectively). The nuclear division index significantly decreased in Tx group relative to the control, PreD and HD groups (P < 0.001). Associations between cytogenetic parameters and creatinine or blood urea nitrogen were found (P < 0.05). To provide longer and better life expectancy of children with CKD and treatment modes, further research is needed to better understand and avoid these effects.

Basal damage and oxidative DNA damage in children with chronic kidney disease measured by use of the comet assay

One consequence of chronic kidney disease (CKD) is an elevated risk for cancer. There is sufficient evidence to conclude that there is an increased incidence of at least some cancers in kidney-dialysis patients. Cancer risk after kidney transplantation has mainly been attributed to immunosuppressive therapy. There are no data evaluating DNA damage in children with CKD, in dialysis patients, or following kidney transplantation. In this study, the comet assay and the enzyme-modified comet assay - with the use of endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) enzymes - were conducted to investigate the basal damage and the oxidative DNA damage as a result of treatment in peripheral blood lymphocytes of children. Children at various stages of treatment for kidney disease, including pre-dialysis patients (PreD) (n=17), regular hemodialysis patients (HD) (n=15), and those that received kidney transplants (Tx) (n=17), comprised the study group. They were compared with age- and gender-matched healthy children (n=20) as a control group. Our results show that the %DNA intensity, a measure of basal damage, was significantly increased in children with CKD (mean ± SD) (5.22 ± 1.57) and also in each of the PreD, HD, and Tx groups [(4.92 ± 1.23), (4.91 ± 1.35), and (5.79 ± 1.94), respectively, vs the healthy children (2.74 ± 2.91) (p<0.001). Significant increases in oxidative DNA damage were only found in the FPG-sensitive sites for the PreD and Tx groups, compared with control and HD groups (p<0.05), suggesting that basal DNA damage was more evident for the PreD, HD, and Tx groups. The findings of the present study indicate a critical need for further research on genomic damage with different endpoints and also for preventive measures and improvements in treatment of pediatric patients, in order to improve their life expectancy.

Gestational Diabetes and Gestational Impaired Glucose Tolerance in 1653 Teenage Pregnancies: Prevalence, Risk Factors and Pregnancy Outcomes

STUDY OBJECTIVE The aim of this study was to determine the prevalence of gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT) in adolescent pregnancies, associated risk factors, and pregnancy complications. DESIGN Retrospective study. SETTINGS Community-based teaching hospital. PARTICIPANTS Results of 1653 pregnant women age ≤ 19 years in 2005-2007 were reviewed. INTERVENTION All pregnant women screened with 50-g glucose challenge test (GCT) and patients with a GCT result ≥ 140 mg/dl underwent a 3-hour 100-g oral glucose tolerance test (OGTT). MAIN OUTCOME MEASURES GDM was diagnosed with at least two abnormal results and GIGT was diagnosed with one abnormal result. GDM and GIGT cases were evaluated for the presence of any associated risk factors and effects of presence of risk factors on pregnancy outcomes. RESULTS The prevalence of GDM was 0.85% (95% CI, 0.41-1.29), GIGT was 0.5% (95% CI, 0.15-0.81) and GDM+GIGT was 1.35% (95% CI, 0.78-1.88) by Carpenter and Coustan criteria. 68% of patients had at least one of the risk factors including body mass index ≥ 25, family history of diabetes and polycystic ovary syndrome (PCOS). Only 9.1% (n = 2) of them required insulin for glucose regulation during pregnancy with 9.1% (n = 2) macrosomia rate. All patients were primiparous and cesarean delivery rate was 27.3% (n = 6). We could not find any effect of presence of risk factors on pregnancy outcomes in GDM and GIGT cases. CONCLUSION We demonstrated that GDM and GIGT are strongly associated with high BMI before pregnancy, PCOS, and family history of diabetes. Since GDM is a state of prediabetes, it is important to diagnose in adolescent pregnancies considering their life expectancy to take preventive measures to avoid diabetes mellitus.

Liddle syndrome in a Turkish family with heterogeneous phenotypes.

Liddle syndrome (LS) is a familial disease characterized by early onset hypertension (HT). Although regarded as rare, its incidence may be greater than expected because the classical findings of hypokalemic metabolic alkalosis with suppressed renin and aldosterone levels are not consistently present. Herein, we present the case of an adolescent boy and maternal relatives who were followed up with misdiagnosis of essential HT for a long duration. Clinical diagnosis of LS was confirmed on genetic analysis. Despite carrying the same mutation, the index patient and the family members manifested heterogeneous phenotypes of the disease including age at presentation, degree of HT, presence of hypokalemia and renal/cardiac complications. LS should be considered in the differential diagnosis of HT in children with a strong family history of HT resistant to conventional treatment; and genetic screening should be performed in these circumstances.

The use of intravesical hyaluronic acid for recurrent urinary tract infections in children: a case-series study

Abstract Background: This is the first study performed to evaluate the effects of intravesical hyaluronic acid (IHA) instillation on diminishing the frequency of recurrent urinary tract infections (UTIs) in children. Methods: Fifteen children (10 girls, 5 boys) with recurrent UTIs were divided into two groups as either complicated (group 1) (with accompanying disorders including vesicoureteral reflux or neurogenic bladder) or uncomplicated patients (group 2). After administration of weekly four sessions of IHA therapy the patients were followed-up monthly for 2 years and classified as responsive (complete/partial) or unresponsive to treatment. Results: 53.3% of the patients with recurrent UTIs were complicated. In group 1 (n = 8), complete and partial response rates were 62.5% (n = 5) and 25% (n = 2), respectively. There was no response in 12.5% (n = 1) of the cases in group 1. In group 2 (n = 7), complete and partial response rates were 71.4% (n = 5) and 14.3% (n = 1), respectively. In this group, 14.3% (n = 1) of the patients were found to be unresponsive to IHA treatment. No side effects were observed in any of the patients. Conclusions: IHA administration is considered as an effective treatment modality which significantly reduces the prevalence of or even provides complete recovery from recurrent UTIs in childhood. Therefore, it is believed that this approach can be used as a promising alternative to widespread use of antibiotics in this patient group.

Changing trends in pediatric renal biopsies: analysis of pediatric renal biopsies in national nephrology registry data

Abstract Renal biopsy is the gold standard method for determining the diagnosis, treatment, and prognosis in children with renal disease. This study aims to evaluate the histopathological features of pediatric renal biopsies obtained from the national nephrology registry in the last two decades. Data recorded in the Turkish Society of Nephrology Registry System (TSNRS) in 1991 as well as in between 2001 and 2010 were analyzed. A total of 3892 biopsies were recorded; with the least number in 1991 (total 103 biopsies from 17 centers) and the highest number in 2008 (total 654 biopsies from 23 centers). Glomerular diseases constituted the main group in the registry (62.64%), followed by systemic diseases (20.06%). Focal and segmental glomerulosclerosis (FSGS) and Henoch–Schönlein purpura (HSP) nephritis (IgA vasculitis) were the most common glomerular and systemic diseases, respectively. Overall prevalence of renal amyloidosis and membranous nephropathy (MN) was quite low (1.87% and 1.56%, respectively) in all periods. Compared to 1991, there was an increasing trend in the frequencies of certain disorders including hemolytic uremic syndrome (HUS), IgA nephropathy, and HSP nephritis; and there was a decrease in acute proliferative glomerulonephritis (GN) in 2008. As well as demonstrating the etiologies of renal diseases which can only be identified by renal biopsies, this study provides important information regarding the changing patterns of histopathological findings due to better management of pediatric renal diseases over the years in Turkey.

The Association Between Plasma Ferritin Level and Simple Febrile Seizures in Children.

Introduction: We conducted this study to determine the role of iron deficiency (ID) as a risk factor for simple febrile seizure (SFS) in 6- to 60-month-old children. Materials and Methods: In this case-control study 100 children aged 6 to 60 months with febrile seizure (FS) (study group) and 100 febrile children without seizures (control group) admitted to Pediatric Departments of Kecioren Training and Research Hospital in between June 2014 and March 2015 were evaluated. Complete blood count, serum iron, plasma ferritin, and total iron binding capacity analyses were performed in children with FS and were compared with controls. Results: Ferritin level was significantly lower in the study group than controls (P<0.05). Compared with the onset of the study (first day), ferritin levels of the study group significantly decreased at the 10th day (P<0.05). At the onset, we were not able to determine ID in 18% of children because of fever. Conclusions: There was a relationship between low plasma ferritin level and SFS. Low plasma ferritin level may be a risk factor for the development of SFS. For preventing the FS attacks, treatment of present ID and oral supplementary iron therapy should be initiated for children with SFS who have a low plasma ferritin.

The evaluation of bone metabolism in children with renal transplantation

This study aims to evaluate BMD and bone biomarkers and to investigate the effects of immunosuppressives on bone disease after RTx. Thirty‐three RTR aged 16.7 ± 3.7 yr and healthy controls (n = 32) were enrolled. There was no difference between pre‐RTx BMD and BMD at the time of study (45.9 ± 30.9 months after RTx), while both values were lower than controls (p < 0.01 and p < 0.05, respectively). Worst BMD scores were obtained at sixth month after RTx (−0.2 ± 0.9) and best at fourth year (1.4 ± 1.3). 25‐hydroxy‐(OH) vitamin D and OPG were higher in RTR (p < 0.001). BMD z scores negatively correlated with OPG and cumulative CS doses at the time of study (r = −0.344, p < 0.05 and r = −0.371, p < 0.05, respectively). Regression analysis revealed OPG as the only predictor of BMD (β −0.78, 95% CI −0.004 to −0.013, p < 0.001). The increase in OPG, a significant predictor of BMD, could either be secondary to graft dysfunction or for protection against bone loss. CS doses should be minimized to avoid their untoward effects on bone metabolism.

A Novel Mutation in the Arginine Vasopressin Receptor 2 Gene Causing Congenital Nephrogenic Diabetes Insipidus

Objective: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by a renal insensitivity to arginine vasopressin (AVP). In the majority of the cases, CNDI is caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. Our objective is to report a novel mutation in the AVPR2 gene causing CNDI in a 6-year-old boy, presenting with growth failure and dull normal cognitive functions. Methods: The proband was the third off-spring of non-consanguineous parents and had polyuria (4.3 L/day), polydipsia (5 L/day). The diagnosis of CNDI was established by a water-deprivation test and a desmopressin challenge test. Genetic studies were also carried out in the mother, siblings and affected family members, since excessive fluid intake and diuresis were also reported in these individuals. All exons of the AVPR2 gene for all participants were amplified and sequenced. Bioinformatics analysis for wild-type and mutant AVPR2 were obtained with Swiss-Model and UCSF Chimera 1.10.2. Results: A novel, hemizygous, missense mutation was identified at the position 80th in exon 2 (p.H80Y) of AVPR2 in the proband. The proband’s mother, maternal aunt and grandmother were heterozygous and his maternal uncle was hemizygous for this mutation. Bioinformatic analysis indicates this mutation would cause significant conformational changes in protein structure. Conclusion: p.H80Y mutation will cause inappropriate folding of the protein compromising water homeostasis via AVPR2 and AVP and leading to diabetes insipidus. We suggest that future functional investigations of the H80Y mutation may provide a basis for understanding the pathophysiology of the NDI in patients with this variant.