Necla Buyan

Polymorphisms in the Vitamin D Receptor Gene and the Risk of Calcium Nephrolithiasis in Children

OBJECTIVE Polymorphism in the Vitamin D Receptor (VDR) gene has recently been reported to be associated with calcium metabolism disorders. This study was conducted to investigate the association of VDR gene polymorphism with the risk of calcium nephrolithiasis. METHODS We investigated the VDR ApaI, BsmI and TaqI polymorphisms, in relation to serum calcium, phosphate, intact parathyroid hormone and 1.25(OH)(2)D(3) in 64 hypercalciuric stone-forming children and 90 healthy children. DNA was isolated from peripheral blood, and genotyping was performed with PCR-based methods. RESULTS The frequency of ApaI AA genotype was significantly higher in the children with calcium nephrolithiasis than the controls (chi(2)=9.5; p=0.008). The distribution of BsmI and TaqI genotypes in stone-forming patients was similar to those in the control group. There was a significant association between TaqI TT genotype and the strength of the family history. The patients with TT genotype were observed to have a 8 times more risk than patients with Tt/tt genotype for recurrent stone episodes (OR 8, 95%CI 1.61-39.6). CONCLUSION VDR genotype determination may provide a tool to identify individuals who are at a risk for calcium nephrolithiasis.

Unresponsiveness to Colchicine Therapy in Patients with Familial Mediterranean Fever Homozygous for the M694V Mutation

Objective. More than 50 disease-associated mutations of the Mediterranean fever gene (MEFV) have been identified in familial Mediterranean fever (FMF), some of which were shown to have different clinical, diagnostic, prognostic, and therapeutic implications. The aim of our study was to define the frequency of mutation type, genotype-phenotype correlation, and response to colchicine treatment in patients with FMF. Methods. This study included 222 pediatric FMF patients. All patients were investigated for 6 MEFV mutations. Then patients were divided into 3 groups according to the presence of M694V mutation on both of the alleles (homozygotes), on only 1 allele (heterozygotes), and on none of the alleles, and compared according to their phenotypic characteristics and response to treatment. M694V/M694V was denoted Group A, M694V/Other Group B, and Other/Other, Group C. Results. Complete colchicine response was significantly lower while the rate of unresponsiveness was significantly higher in Group A compared to Groups B and C (p = 0.031, p < 0.001 and p = 0.005, p = 0.029, respectively). No differences except proteinuria were found between the phenotypic features of 3 groups. Group C had the lowest rate of proteinuria development (p = 0.024). All the amyloidosis patients were in Group A. Conclusion. Our results indicate that the M694V/M694V mutation is associated with lower response to colchicine treatment. Therefore, patients homozygous for M694V/M694V may be carrying an increased risk for development of amyloidosis.

Henoch-Schönlein nephritis: a nationwide study.

Background/Aim: The aim of this retrospective study was to evaluate the presentation, clinical and pathological manifestations and outcome of the Henoch-Schönlein purpura (HSP) nephritis in children. Methods: Clinical and laboratory data of 443 children with HSP nephritis aged between 3 and 16 years from 16 pediatric nephrology reference centers were analyzed retrospectively. The biopsy findings were graded according to the classification developed by the International Study of Kidney Disease in Children (ISKDC). Results: Renal biopsy was performed in 179 of the patients with HSP nephritis. The most common presenting clinical finding in patients who were biopsied was nephrotic range proteinuria (25%) which was followed by nephritic-nephrotic syndrome (23.5%). The biopsy findings according to the ISKDC were as follows: class I: 8.3%; II: 44.1%; III: 36.3%; IV: 6.7%; V: 3.3%; VI: 1.1%. All of the patients who developed end-stage renal disease had nephritic-nephrotic syndrome at presentation. Of 443 patients, 87.2% had a favorable outcome and 12.8% had an unfavorable outcome. The overall percentage of children who developed end-stage renal disease at follow-up was 1.1%. Logistic regression analysis did not show any association of initial symptoms and histology with outcome. Conclusion: In the presented cohort, the presence of crescents in the first biopsy or presenting clinical findings did not seem to predict the outcome of HSP nephritis in children. We conclude that children with HSP nephritis even with isolated microscopic hematuria and/or mild proteinuria should be followed closely.

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.

Circulating adhesion molecules ICAM-1, E-selectin, and von Willebrand factor in Henoch-Schönlein purpura.

Adhesion molecules play an important part in leucocyte transendothelial migration and thus may provide a useful marker of surface expression at inflammatory sites. In 20 patients with Henoch-Schönlein purpura serum intercellular adhesion molecule 1 (ICAM-1), E-selectin, and plasma von Willebrand factor (vWF) were determined by ELISA during the active and inactive phase of the disease. Twelve healthy children were studied as a control group. Serum ICAM-1 concentrations increased during the active phase of the disease and differed significantly compared with the inactive phase (p < 0.05). However ICAM-1 in the active phase did not differ significantly compared with controls (p = 0.08). Serum E-selectin concentrations did not differ in the active and inactive phase of the disease. By contrast, vWF increased in the active phase of the disease and differed significantly compared with inactive disease and control groups (p < 0.01). Considering the adhesion molecules and vWF, only vWF correlated well with the C reactive protein measurement in the active phase, which is considered a good marker of disease activity. These data suggest that plasma vWF is a good marker of vascular inflammation and endothelial damage. Circulating ICAM-1 might be an additional parameter in some of the patients.

Nitric oxide in Henoch-Schönlein purpura.

Objective : To assess the value of nitric oxide (NO) production on the disease activity in children with Henoch-Schönlein purpura (HSP) by measuring serum nitrate levels and urinary nitrate excretion as an indicator for NO production. Methods : The study group consisted of 25 patients and 20 healthy children. We measured serum nitrate, urinary excretion of nitrate, and CRP levels in the acute phase and after remission. Results : Serum nitrate levels in the acute phase of the disease were found to be increased compared to the remission phase (28.67 - 10.3 mmol/l, 14.16 - 2.02 mmol/l) (p<0.001) and the control group (13.15 - 2.28 mmol/l) (p<0.001). Urinary nitrate excretion in the acute phase of the patients (15.32 - 9 mmol/mg) was increased compared to that in the remission phase (8.26 - 4.3 mmol/mg) (p=0.016) and in the control group (7.24 - 4.9 mmol/mg) (p<0.01). Conclusion : Serum NO and urinary nitrate excretion were found to be elevated in patients with HSP and this increase was associated with activation of the disease rather than its severity. These findings suggest a role for NO in the pathogenesis of HSP, but nitric oxide in HSP should be further studied in order to elucidate the pathophysiology of the disease

Sonographic demonstration of intestinal involvement in Henoch-Schönlein syndrome

We evaluated the efficacy of intestinal sonography in the diagnosis of gastrointestinal involvement of Henoch-Schönlein syndrome (HSS). Intestinal sonography was performed in 20 children who were clinically diagnosed as HSS and sonographic findings of the intestinal system were reviewed. Out of 20 patients, 10 who suffered from abdominal pain demonstrated sonographic findings consistent with small intestinal involvement (dilatation of intestinal segments, hypomotility, and eccentric thickening of the intestinal wall). Our results reveal that sonography of the intestine may be useful in the evaluation of the involvement of HSS.

Adiponectin levels and arteriosclerotic risk factors in pediatric renal transplant recipients

Abstract:  ADPN, a recently discovered adipocytokine, has attracted great attention because of its anti‐atherogenic properties. It was suggested as a protective factor for the cardiovascular system because of its close correlation with several risk factors. Our aim was to investigate serum ADPN levels in pediatric RTR and to document possible relationships between ADPN and arteriosclerotic risk factors. Twenty‐one RTR, aged 16.3 ± 4.0 yr, and 23 healthy age and sex‐matched control subjects were enrolled in this study. Serum lipid/lipoprotein fractions, homocysteine and ADPN levels as well as intima‐media thickness of the cIMT were determined in both groups. Significantly higher serum ADPN (p < 0.001) and homocysteine (p < 0.05) levels as well as higher cIMT (p < 0.001) were found in RTR compared with the control subjects, whereas apolipoprotein B and lipoprotein (a) levels were not significantly different. HDL cholesterol was positively correlated with log ADPN (r = 0.585, p < 0.01). There were inverse correlations between log time post‐transplantation and log ADPN as well as HDL cholesterol (r = −0.438, p < 0.05 and r = −0.578, p < 0.05, respectively). There were no correlation between log ADPN, log homocysteine, log apolipoprotein B, lipoprotein (a), creatinine clearance and cumulative steroid dose. Despite reasonable lipid profiles and remarkably elevated ADPN levels, our pediatric RTR with stable graft function displayed a risk for arteriosclerosis because of increased cIMT and mild hyperhomocysteinemia. Regarding the close positive correlation between ADPN and HDL cholesterol, it could be speculated that ADPN is a novel negative surrogate marker of arteriosclerosis. To our knowledge, this is the only report investigating levels and diverse correlates of ADPN in a pediatric RTR group. Further studies in larger groups of recipients are needed to clarify the interaction between arteriosclerotic risk factors and ADPN.

The importance of99mTc DMSA scanning in the localization of childhood urinary tract infections

The use of99mTechnetium dimercaptosuccinic acid (99mTc DMSA) scanning for the early diagnosis of upper urinary tract infections has been preferred for a few years. In this research we investigated the use of99mTc DMSA scanning in the localization of renal parenchymal involvement in urinary tract infection. Twenty-four children presenting with first acute urinary tract infection were studied. Investigations included physical examination, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antibody-coated bacteria (ACB) and early99mTc DMSA scanning.99mTc DMSA scanning was taken as the gold standard method in determining renal parenchymal inflammation. According to the99mTc DMSA scanning the sensitivity of clinical findings was 57.14%, WBC 23.80%, ESR 33.33%, CRP 14.28% and ACB 71.42% in the localization of urinary tract infection. We propose early99mTc DMSA scanning performed around the time of infection as a good technique for localization of the level of infection in the urinary tract.

High serum adiponectin levels during steroid-responsive nephrotic syndrome relapse.

Adiponectin (ADPN), exclusively expressed and secreted from adipocytes, is a recently discovered protein hormone with anti-atherogenic and anti-inflammatory properties in contrast to other well-known adipocytokines. It has independent negative associations with obesity and hyperinsulinemia/insulin resistance. Apart from chronic renal failure, nephrotic syndrome was suggested as the only renal disease condition associated with raised plasma ADPN levels in adults. We aimed to evaluate the effect of nephrotic state on serum adiponectin (ADPN) levels in pediatric patients with steroid-responsive nephrotic syndrome (SRNS) by comparing the levels in relapse and remission as well as in control subjects and documenting possible relationships between ADPN and proteinuria as well as serum protein/lipid parameters. 34 patients with SRNS and 22 healthy age, sex and BMI-matched control subjects were enrolled into the study. 15 of the 34 SRNS patients had active diseases, and these were known as the SRNS-relapse group (ten relapsed and five newly-diagnosed patients), while the remaining 19 were in complete remission (the SRNS-remission group). Serum ADPN levels, blood chemistry (protein/albumin, triglyceride (TG), cholesterol (Cho) and lipoprotein levels) and 24-hour proteinuria were studied. ADPN levels were determined by ELISA. As expectedly, there were significant alterations in serum protein-lipid parameters and 24-hour proteinuria levels in SRNS patients consistent with their disease activity. SRNS-relapse patients had substantially higher ADPN levels (36.77±15.06 (5.61–59.41, median 39.84) μg/ml), compared to those in SRNS-remission and control groups (14.17±6.02 (3.28–29.40, median 12.80) μg/ml and 11.84±7.53 (2.81–31.46, median 10.85) μg/ml, respectively, p=0.001). There were strong positive correlations between serum ADPN levels and Cho (r=0.637, p=0.000), TG (r=0.516, p=0.002), low density lipoprotein (r=0.614, p=0.000) levels and 24-hour proteinuria (r=0.828, p=0.000) levels, whereas protein (r=−0.695, p=0.000) and albumin (r=0.732, p=0.000) levels were inversely correlated with ADPN levels. Regression analysis showed a significant correlation between ADPN and proteinuria (p=0.000). In conclusion, remarkably increased serum ADPN levels were detected in SRNS-relapse compared to those in SRNS-remission. This phenomenon might be the reflection of a compensatory response to nephrotic state characterized by massive proteinuria, hypoalbuminemia and hyperlipidemia.