Nazlı Kara

Implications of certain genetic polymorphisms in scarring in vesicoureteric reflux: Importance of ace polymorphism

Polymorphisms of the renin-angiotensin system (RAS) have been shown to affect renal prognosis in a number of diseases. We examined the influence of deletion (D) and insertion (I) polymorphism in the angiotensin I-converting enzyme (ACE) gene and the other polymorphic markers of RAS, and that of plasminogen-activator inhibitor-1 (PAI-1) on renal scarring in reflux nephropathy. Ninety-four children with third- or fourth-degree reflux were the subject of the study. They were stratified into two groups according to the technetium-99m-dimercaptosuccinic acid (DMSA) findings: the first group consisted of 41 patients with no scar formation. In the second group (n = 53), there was significant scar formation in the refluxing units. ACE levels, ACE gene, angiotensin-1 receptor (AT1) A1166C, angiotensinogen (ATG) M235T, and PAI-1 4G/5G polymorphisms were studied. In the second group with scarred kidneys, 18 patients had decreased renal function. The frequency of patients homozygous for the D allele was significantly greater in the second group with scar formation in the refluxing units compared with the first group of patients (P < 0.005). On multivariate analysis, the DD genotype was the only factor that had a significant impact on renal scar formation, introducing a 4.9-fold risk (P < 0.05, 95% confidence interval). We were unable to find any correlation with the presence ofDD genotype and hypertension, decreased renal function, proteinuria, or sex of the patient. DDgenotype correlated with the serum ACE levels (P < 0.005). AT1and ATGpolymorphisms and PAI-1 polymorphism did not correlate with scar formation or any of the parameters. This study provides evidence that the DDgenotype of ACE may be a genetic susceptibility factor contributing to adverse renal prognosis in reflux nephropathy; namely, scar formation. The role of the synergism between the aforementioned genetic polymorphisms can be enlightened with larger patient groups, possibly through multicenter studies.

MEFV Mutations Modify the Clinical Presentation of Henoch-Schonlein Purpura

Objective To investigate the prevalence of MEFV gene mutations in Turkish patients with Henoch-Schönlein purpura (HSP) but with no symptoms of familial Mediterranean fever (FMF). In addition, we assessed the clinical and laboratory characteristics of HSP patients with and without MEFV mutations. Methods Eighty pediatric patients with HSP (44 boys and 36 girls) were enrolled. Blood for mutation analysis was obtained either at the time of the diagnosis of HSP or during followup visits in previously diagnosed patients. No patient had the diagnosis of FMF in their history and in the followup period. Exon 10 of the MEFV gene was screened, together with p.E148Q mutation analysis. Results Twenty-seven (34%) patients were found to be heterozygous for one of the screened MEFV mutations; p.M694V in 16, p.M680I in 5, p.V726A in 3, and p.E148Q in 3 patients. Patients with MEFV mutations were younger than those without mutations and they had edema and arthritis more frequently. Also, the frequencies of elevated erythrocyte sedimentation rate and C-reactive protein values were found to be significantly higher in patients who had MEFV mutations. Conclusion Alterations in the MEFV gene are important susceptibility factors for the development of HSP and also affect the clinical presentation of it.

Global left-ventricular function by tissue Doppler imaging in pediatric dialysis patients

Cardiovascular abnormalities are observed in most children with end-stage renal disease (ESRD). The aim of this study was evaluation of left-ventricular (LV) myocardial performance using tissue-Doppler imaging (TDI) in patients with ESRD. Twenty-five patients with ESRD and 25 healthy gender- and age-matched control subjects were assessed with conventional M-mode echocardiography, pulsed-wave Doppler (PWD), and TDI. Myocardial Performance Index (MPI) and LV mass index (LVMI) were calculated. MPI and conventional echo-Doppler indices were compared in the ESRD and control groups. Significant differences were present in the mean systolic and diastolic blood pressure (BP) between children with ESRD and healthy children (p = 0.007 and p < 0.001, respectively). The mean LVMI was significantly greater in the patient group (p < 0.001). The tissue-Doppler MPI of patients was significantly higher than that in healthy children (p < 0.001). LVMI was significantly correlated with systolic and diastolic BP. MPI obtained by TDI was significantly correlated with LVMI. Our study confirms that LV dysfunction is present in patients with ESRD and hypertension is an important risk factor.

Cardiac involvement in childhood polyarteritis nodosa.

In this report, we evaluated the cardiac findings of 15 children with polyarteritis nodosa. The age range of the patients was 4-14 years; with a mean of 10 years. All have had systemic involvement of the disease. The most common findings in cardiac evaluation were diminished left ventricular systolic functions and mild mitral and/or tricuspid valve regurgitation. One patient had pericardial thickening with no effusion. One had sinus tachycardia. There were no signs of myocardial infarction or ischemia clinically or electro-cardiographically. In conclusion, we did not find cardiac complications, such as pericarditis or myocardial infarction, to be as frequent as in previous reports. However, even in asymptomatic patients, systolic dysfunction or valvular involvement were common findings in patients with polyarteritis nodosa, which were not reported previously. These findings may be due to the histological changes of the myocardium or atrioventricular valves. Although these were not severe and fatal lesions, long-term follow-up of these patients with echocardiography may help to determine the course of cardiac involvement.

Application of the new pediatric criteria and Tel Hashomer criteria in heterozygous patients with clinical features of FMF

Recently, a new set of criteria was established for the diagnosis of familial Mediterranean fever (FMF) in childhood. The aim of this study is to validate the new criteria set among heterozygous patients with clinical features of FMF. The study group consisted of FMF patients, who had a mutation at a single allele, who were followed in four pediatric nephrology–rheumatology centers in Turkey. Patients were evaluated by the new criteria set and also by the Tel Hashomer criteria. According to the new criteria, the diagnosis of FMF was established by the presence of two or more of five criteria (fever, abdominal pain, chest pain, arthritis, family history of FMF). The study group consisted of 110 FMF (54 male, 56 female) patients. Majority of the patients had heterozygous pM694V mutation (65%). The sensitivity of the new criteria set and that of the Tel Hashomer criteria in our study group were found to be 93% and 100%, respectively. In conclusion, this study designates that sensitivity of the new criteria set is also high in patients who had a mutation at a single allele.

Primary nephrotic syndrome during childhood in Turkey

Abstract Background : Minimal change nephrotic syndrome (MCNS) is the most common cause of primary nephrotic syndrome (NS) during childhood. However, recent studies from different countries have reported an increasing incidence of focal segmental glomerulosclerosis (FSGS) in children.

Hypertension and left ventricular hypertrophy in pediatric peritoneal dialysis patients: ambulatory blood pressure monitoring and echocardiographic evaluation.

Background: Hypertension is a frequent complication of end-stage renal disease and left ventricular hypertrophy (LVH) is common in patients with poorly controlled hypertension. The aim of this study was to evaluate hypertension in pediatric peritoneal dialysis (PD) patients, to compare casual and ambulatory blood pressure (BP) measurements and to evaluate the impact of BP parameters on LVH. Methods: The study comprised 25 PD patients (9 M, 16 F; mean age 14.14 ± 3.32 years) that have been followed in outpatient clinics. Medical records were reviewed for demographic features; casual BP measurements, ambulatory blood pressure monitoring (ABPM) and echocardiographic evaluation were applied to all patients. Results: The mean 24-hour and daytime systolic blood pressure (SBP) values were found to be higher than casual SBP (p < 0.001). Significant difference was present in the frequency of hypertension between casual SBP (32%) and the mean daytime SBP (56%) (p < 0.05). Nighttime systolic hypertension was detected in 14 (56%) and diastolic hypertension in 16 (64%) patients. Elevated daytime SBP load and DBP load were detected in 64 and 76% of the patients, respectively. Elevated nighttime SBP load and DBP load were detected in 72% of the patients. Seventeen (68%) patients had attenuated dipping for SBP. The mean left ventricular mass index (LVMI) was 52.65 ± 18.17 g/m2.7 and 13 (52%) patients had LVH. LVMI was significantly correlated with casual BP measurements and the majority of ABPM parameters. Conclusion: The majority of pediatric PD patients had BP abnormalities in which severity was most accurately assessed with ABPM. Casual BP and majority of ABPM parameters were found to be significantly correlated with LVMI. Ambulatory blood pressure monitoring should be performed in all pediatric PD patients.

Renal Involvement in Childhood Vasculitis

Background/Aims: Renal involvement comprises one of the major organ involvements in childhood vasculitis and has also an important role in the long term prognosis. The aim of this retrospective study was to analyze the demographic, clinical, laboratory features, and the treatment modalities of patients with vasculitis who had renal involvement. Methods: Patients with the diagnosis of vasculitis who had been followed in two pediatric nephrology centers between 1990 and 2005 were analyzed retrospectively.Patients with renal involvement were selected and further evaluated. Results: The study population consisted of 152 of 816 patients with vasculitis. Renal involvement was seen in 134 patients (17%) with Henoch-Schönlein purpura(HSP), 14 patients (45%) with polyarteritis nodosa(PAN), 3 patients with Takayasu arteritis (TA) (50%) and in 1 Wegener granulomatosis (WG) patient.Themean age of patients with renal involvement was 9.2 ± 0.91 years in the HSP group. Hematuria with proteinuria was the most common renal finding and joint manifestations were seen less in this group. During the follow-up, only 1 patient developed chronic renal failure. Proteinuria, hematuria and aneurysms were seen in 26, 35 and 57% respectively in the PAN group. Only 1 patient (3.2%) had developed chronic renal failure.All 3 patients with TA had bilateral renal arterial involvement. Conclusion: Renal involvement constitutes an important part of childhood vasculitides. With the institution of early and aggressive immunosuppressive treatment significant improvement in the long-term survival of these patients can be achieved.

The association between obesity, hypertension and left ventricular mass in adolescents.

Abstract Background: Obesity and hypertension (HT) are well known cardiac risk factors. Our goal was to show that even if arterial blood pressure (BP) measurements of obese adolescents are normal during clinical examination, ambulatory blood pressure monitoring (ABPM) can be high, may include cardiac involvement and can also detect left ventricular mass indices (LVMI) value for obese adolescents to diagnose left ventricular hypertrophy (LVH). Methods: This study included 130 children (57 obese hypertensive, 36 obese normotensive, 14 normal weight hypertensive and 23 normal weight normotensive). Adolescents whose BP was measured during clinical examination, after 24-h BP was detected using ABPM, were examined with echocardiography for calculation of LVMI to determine cardiac risk factors for LVH. Results: There was a significant difference between the LVMI of obese-normotensive and obese-hypertensive adolescents, which showed the effect of obesity on LVMI independent of HT. Twenty (35.7%) of 56 obese adolescents with HT detected with ABPM had normal BP measurements during clinical examination. Dipper and nondipper features of obese adolescents were significantly higher in ABPM than those with normal body mass index. When the cutoff LVMI value for LVH was set at ≥38 g/m2.7, 38.9% of obese-normotensive and 50.9% of obese-hypertensive subjects had LVH; however, when the cutoff value was set at ≥51 g/m2.7, the rates were 2.8% and 19.3%, respectively. Conclusions: Obesity is a risk factor for LVH independent of HT. To identify masked HT, 24-h ABPM and cardiac examination should be routinely performed in obese adolescents. Using a limit of LVMI ≥38 g/m2.7 in evaluating LVH secondary to HT in obese individuals may lead to an overestimated diagnosis rate of LVH.