Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study.

BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study.

BACKGROUND: The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. METHODS: A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. RESULTS: Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. CONCLUSIONS: Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Molecular analysis of the AGXT gene in patients suspected with hyperoxaluria type 1 and three novel mutations from Turkey.

Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive disease, caused by the defect of AGXT gene encoding hepatic peroxisomal alanine glyoxylateaminotransferase (AGT). This enzyme is responsible for the conversion of glyoxylate to glycine. The diagnosis of PH1 should be suspected in infants and children with nephrocalcinosis or nephrolithiasis. Early diagnosis and treatment is crucial in preventing disease progression to end stage kidney disease (ESKD). In this study, AGXT gene sequence analyses were performed in 82 patients who were clinically suspected (hyperoxaluria and nephrolithiasis or nephrocalcinosis with or without renal impairment) to have PH1. Disease causing mutations have been found in fifteen patients from thirteen families (18%). Novel mutations have been found (c.458T>A (p.L153X), c.733_734delAA (p.Lys245Valfs*11), c.52 C>T (p.L18F)) in three of 13 families. There were 3-year lag time between initial symptoms and the time of PH1 is suspected; additionally, 5.5-year lag time between initial symptoms and definitive diagnosis. Consanguinity was detected in 77% of the patients with mutation. After genetic diagnosis, one patient received combined kidney and liver transplantation. AGXT gene sequencing is now the choice of diagnosis of PH1 due to its non-invasive nature compared to liver enzyme assay. Early diagnosis and accurate treatment in PH1 is important for better patient outcomes.

Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

Vitamin D receptor gene polymorphism in children with urinary tract infection.

It is known that small alterations leading to different vitamin D receptor (VDR) alleles affect resistance or susceptibility to infections. In this study, we examined VDR gene polymorphisms in urinary tract infections (UTI), which are common and an important cause of morbidity in children and subsequently of renal scar formation. We evaluated 92 patients diagnosed with UTI and 105 children without prior history of UTI as a control group. The VDR gene polymorphisms BsmI, FokI, ApaI, and TaqI were evaluated in patients and controls. BsmI polymorphism genotype distribution was similar between groups. There was a significant difference between groups for FokI (p =0 < 001); for the ff genotype, the risk of UTI was significantly increased (p < 0.01) ,at 3.94 times higher (odds ratio = 3.94; 95% confidence interval 1.71-9.09). ApaI polymorphism was significantly increased in the control group (p < 0.01) and evaluated as a protective factor. Comparing the TaqI genotype between groups, there was no statistically significant difference, but in both Tt and tt genotypes, there was minimal increased risk of UTI. The results of this study suggest that VDR gene polymorphisms can be important for susceptibility to UTI and renal scar formation. Association between VDR polymorphisms and UTI is in accordance with the understanding of how vitamin D modulates the immune response against infections.

Comparison of infants and children with urolithiasis: a large case series.

We evaluated the demographic features, etiologic risk factors, treatment strategies, and outcome of the infants and children with urolithiasis (UL). A retrospective multicenter study was conducted including 23 Pediatric Nephrology centers in Turkey. The medical records of 2513 children with UL were reviewed. One thousand, three hundred and four boys and 1209 girls (1.1:1) were reported. The mean age at diagnosis was 39.5 ± 35 months (0.4-231 months), and 1262 patients (50.2%) were in the first year of life (infants). Most of the cases with infantile UL were diagnosed incidentally. Microlithiasis (< 3 mm) was found in 794 patients (31.6%), and 64.5% of the patients with microlithiasis were infants. Stones were located in the pelvis-calyces in 63.2% (n: 1530) of the cases. The most common stone type was calcium oxalate (64.6%). Hypocitraturia was the most common metabolic risk factor (MRF) in children older than 12 months, but in infancy, hypercalciuria was more common. Fifty-five percent of the patients had received at least one medical treatment, mostly potassium citrate. At the end of a year's follow-up, most of the patients with microlithiasis (85%) showed spontaneous remission. The rate of spontaneous stone resolution in infants was higher than in children. Spontaneous remission rate was higher in cases with MRF ( - ) stones than in MRF ( +) stones. However, remission rate with medical treatment was higher in cases with MRF ( +) stones. This study represents the results of a large series of infants and children with UL and showed that there are several differences such as underlying metabolic and anatomic abnormalities, clinical course, and stone remission rates between infants and children with urinary stone disease.

Co-existence of chronic renal failure, renal clear cell carcinoma, and Blau syndrome.

Blau syndrome is a rare, multisystem, autosomal-dominant, and granulomatous disorder caused by susceptibility variants in the NOD2 gene. We describe here a 14-year-old girl with Blau syndrome with incidentally diagnosed renal carcinoma. The index case presented with growth retardation and recurrent symmetric arthritis. Her clinical symptoms included bilateral cataract due to recurrent uveitis, camptodactyly, and persistent erythematous rash with ichthyosis. Her two sisters and her mother were affected with combinations of these conditions-symmetric polyarthritis, uveitis, and skin involvement-suggesting an autosomal dominant trait. The index case developed a chronic renal insufficiency, and an abdominal computerized tomography scan revealed a 2.5-cm mass in the left kidney. The histopathological examination showed renal clear cell carcinoma, chronic tubulointerstitial nephritis,and giant cell granulomas in both the tumor and nonneoplastic renal tissue. Granulomatous inflammation was observed in the skin biopsy specimen. The patient was diagnosed with Blau syndrome based on her family history, uveitis, granulomatous inflammation proved by skin biopsy, and polyarthritis. Sequencing of the NOD2 gene showed a heterozygous p.R334Q mutation in all affected family members. To the best of our knowledge, this is the first reported case of a patient with Blau syndrome accompanied by chronic renal failure and renal carcinoma.

Etiology and outcome of acute kidney injury in children.

The aim of this prospective, multicenter study was to define the etiology and clinical features of acute kidney injury (AKI) in a pediatric patient cohort and to determine prognostic factors. Pediatric-modified RIFLE (pRIFLE) criteria were used to classify AKI. The patient cohort comprised 472 pediatric patients (264 males, 208 females), of whom 32.6% were newborns (median age 3 days, range 1-24 days), and 67.4% were children aged >1 month (median 2.99 years, range 1 month-18 years). The most common medical conditions were prematurity (42.2%) and congenital heart disease (CHD, 11.7%) in newborns, and malignancy (12.9%) and CHD (12.3%) in children aged >1 month. Hypoxic/ischemic injury and sepsis were the leading causes of AKI in both age groups. Dialysis was performed in 30.3% of newborns and 33.6% of children aged >1 month. Mortality was higher in the newborns (42.6 vs. 27.9%; p < 0.005). Stepwise multiple regression analysis revealed the major independent risk factors to be mechanical ventilation [relative risk (RR) 17.31, 95% confidence interval (95% CI) 4.88-61.42], hypervolemia (RR 12.90, 95% CI 1.97-84.37), CHD (RR 9.85, 95% CI 2.08-46.60), and metabolic acidosis (RR 7.64, 95% CI 2.90-20.15) in newborns and mechanical ventilation (RR 8.73, 95% CI 3.95-19.29), hypoxia (RR 5.35, 95% CI 2.26-12.67), and intrinsic AKI (RR 4.91, 95% CI 2.04-11.78) in children aged >1 month.

A patient with Bartter syndrome accompanying severe growth hormone deficiency and focal segmental glomerulosclerosis.

Bartter syndrome is a rare autosomal recessive, salt-losing disorder characterized by hypokalemic hypochloremic metabolic alkalosis. A 10-year-old boy had severe growth retardation (height standard deviation score -8.15). He had a thin, triangular face, prominent ears and forehead, and big eyes. Megacystis, bilateral hydroureteronephrosis, and residual urine were detected in ultrasonography, but there was no vesicoureteral reflux. Lumbosacral magnetic resonance (MR) showed posterior disc bulging at L4-5. Serum sodium and chloride levels were normal, but mild hypokalemia was overlooked initially. During follow-up, hypokalemic hypochloremic metabolic alkalosis developed, with high urinary chloride and potassium excretion (52 and 43 mEq/L, respectively). The patient, with renal salt loss, was thought to have classic Bartter syndrome due to absence of nephrocalcinosis, presence of persistent hypercalciuria and sensorineural deafness, and presence of relatively mild clinical and laboratory findings, except polyuria initially. The child was treated with indomethacin, spironolactone, and oral potassium in addition to growth hormone (GH). During treatment, he had considerable increase in weight and height compared with the period of GH therapy only. We present this case because, although growth retardation is a major feature of Bartter syndrome, associated GH deficiency is rarely reported in the literature. Diagnosis of Bartter syndrome was made later, as our patient was followed for megacystis and megaureter secondary to the neurogenic bladder and GH deficiency initially; and proteinuria associated with focal segmental glomerulosclerosis responded to treatment for Bartter syndrome.

Is Helicobacter pylori related to endothelial dysfunction during childhood?

BACKGROUND: Helicobacter pylori infection has been proposed to have a role in the development of atherosclerosis preceded by endothelial dysfunction. The aim of the present study was to determine if a relationship exists between H. pylori infection in childhood and endothelial dysfunction and level of high-sensitivity C-reactive protein (hsCRP). METHODS: Between October 2003 and November 2004, 28 subjects who were anti-H. pylori IgG-positive and 25 who were anti-H. pylori IgG-negative were included in the study. Mean ages of the H. pylori-positive and negative groups were not significantly different. Endothelial functions were evaluated on Doppler ultrasonography of the brachial artery. Percent ratio of the change in systolic diameter during hyperemic phase to the basal diameter was evaluated. Each subject's serum was tested for hsCRP, homocysteine and lipids. RESULTS: Percent ratio of the change in systolic diameters during hyperemic phase to the basal diameter was not significantly different between the H. pylori-negative and -positive groups (P > 0.29). Mean levels of hsCRP were also not significantly different (1.48 +/- 1.8 g/dL vs 2.35 +/- 3.33 g/dL; P > 0.24). Similarly, serum levels of lipids and homocysteine were not significantly different (P > 0.05 for all lipids). CONCLUSIONS: Non-invasive techniques used in the present study were not indicative of early findings of atherosclerosis in H. pylori infection during childhood. Further studies are required to evaluate the relationship between early endothelial dysfunction and H. pylori infection in children with cardiovascular risk factors.

Kidney stone and urinary bladder telangiectasia in a patient with TAR syndrome.

TAR syndrome is a congenital malformation syndrome characterized by bilateral absence of the radius and thrombocytopenia. The known urinary anomalies are duplex ureter, dilatation of renal pelvis, horseshoe kidney and functional problems like vesicoureteral reflux and pyelonephritis. In this report of a case with TAR syndrome, a kidney stone and bladder telangiectasia were found coincidentally during the investigation of hematuria. TAR syndrome is discussed in the light of the medical literature. To our knowledge, no case has been reported demonstrating nephrolithiasis and bladder telangiectasia in TAR patients.

Etiologic risk factors and vitamin D receptor gene polymorphisms in under one-year-old infants with urolithiasis.

The incidence of urinary tract stones in infancy has been increasing in Turkey. Risk factors and vitamin D receptor (VDR) gene polymorphisms were investigated in infants aged < 1 year who had stones. Forty infants with urinary tract stones and 80 infants without stones, aged < 1 year were enrolled in this study. Detailed surveys were taken of all infants, metabolic parameters and ApaI and FokI VDR gene polymorphisms were investigated. Infants with stones tended to be more commonly fed formula and multivitamins (vitamins A, C, D) (p < 0.05). Positive family history came into prominence in the stony group (p < 0.05). There were no significant differences in ApaI and FokI VDR gene polymorphisms between the groups with stones and the control groups. However, CA genotype of ApaI polymorphism was associated with family history and C allele of ApaI was related with family history and hypercalciuria (p < 0.05). Hypercalciuria emerged as an underlying metabolic abnormality in the etiology of stones, and was observed at a rate of 38%. Infants who are given formula and multivitamins for vitamin D supplementation are at increased risk for the formation of urinary tract stones. VDR gene polymorphisms cause the formation of urinary tract stones and affect calcium (Ca) metabolism.

Henoch-Schonlein purpura, post-streptococcal glomerulonephritis and acute rheumatic carditis after Group A ß-haemolytic streptococcal infection.

Besides association with acute rheumatic fever (ARF) and acute glomerulonephritis (APSGN), in up to 40% of cases, Group A ß-haemolytic streptococcal (GABHS) infections are also implicated as a trigger for Henoch-Schonlein purpura (HSP). A 7-year-old girl with GABHS throat infection who developed HSP, APSGN and rheumatic carditis is reported. She presented with palpable purpura and arthritis in both ankles and later developed carditis characterised by mitral/aortic regurgitation and glomerulonephritis characterised by mixed nephritic/nephrotic syndrome. She had a raised anti-streptolysin titre (ASOT), blood urea nitrogen and creatinine and hypocomplementaemia (C3), and renal biopsy demonstrated endocapillary and extracapillary proliferative glomerulonephritis with crescents. Immunofluorescence microscopy demonstrated a 'full house' of immunoglobulin and complement, viz. IgA + 2, IgG + 3, IgM + 2, C3c + 1, Clq + 2 with predominantly IgG deposition. One week earlier, her 4-year-old sister had presented to another hospital with HSP complicated by microscopic haematuria, nephrotic-range proteinuria and gastro-intestinal involvement, and with raised ASOT and low C3 levels. Although HSP has been associated with either ARF or APSGN, this is the first case of a child with HSP, ARF and APSGN in combination.

Evaluation of association between hepatitis A and Helicobacter pylori infections and routes of transmission.

Previous research about coexistence of Helicobacter pylori (HP) and hepatitis A virus (HAV) infections and the factors that increase their prevalence has suggested that the route of transmission of HP infection includes oral-oral and water-foods as well as the fecal-oral route. The aim of this study was to evaluate the routes of transmission of HP by comparing the seroprevalences of HP and HAV in children. One hundred and two children aged 1-18 years living in rural and urban regions of Izmir were included in this study. Anti-HP IgG and anti-HAV IgG antibodies were measured via enzyme immunoassay method. Seropositivities for HP and HAV were 56.8% and 51.9%, respectively. Seroprevalence for both infections increased with increasing age. However, a significant difference could not be detected between rural and urban areas. Sex did not have a significant effect. There was no infection in 22.1% of children, while 30.8% had both of the infections. 21.1% were positive only for HAV while 26% were positive only for HP. No significant correlation between seroprevalences of HP and HAV was detected. This study suggests the existence of various other routes of transmission of HP apart from the fecal-oral route.

Evaluation of voiding dysfunctions in children with chronic functional constipation.

There are controversial results about the role of dysfunctional bowel emptying in disorders of the urinary tract like urinary tract infection (UTI), vesicoureteral reflux (VUR) and enuresis. Constipation may cause UTI, enuresis and VUR due to the uninhibited bladder contraction. The aim of this study was to investigate the frequency of nocturnal enuresis, UTI and instability symptoms in chronic functional constipation (CFC). This study included 38 children with CFC and 31 children as the control group. Detailed past and present history of UTIs or symptoms pointing to this diagnosis, enuresis, encopresis, urgency and urge incontinence was obtained from both groups as well as the family history of UTI. Urinalysis, urine culture and stool parasite analysis as well as abdominal ultrasonography were performed on both groups. Age range of the children with CFC was 6-192 months (mean +/- standard deviation (SD) 63.5 +/- 51 months); that of the control group was 4-180 months (mean +/- SD 82 +/- 46.2 months). Frequency of UTI and urgency was significantly higher in the CFC group. However, frequencies of urge incontinence, nocturnal enuresis, and genitourinary abnormalities were not different between the two groups. In conclusion, risk of UTI and urgency is increased in CFC, but that of other voiding dysfunctions like urge incontinence do not change significantly. Therefore, we suggest that UTI and urgency should be questioned in children with CFC and vice versa.

Do patients with neurogenic bladder treated with clean intermittentcatheterization need antibacterial prophylaxis?

BACKGROUND/AIM: In this study, we investigated the effectiveness of antibiotic prophylaxis (ABP) with respect to the incidence of symptomatic urinary tract infections (UTIs) and evaluated the development of renal scarring in patients treated with clean intermittent catheterization (CIC). MATERIALS AND METHODS: A total of 22 patients were included in the study. The patients were administered ABP in the first year (the ABP-received period) but not in the second year (the ABP-discontinued period). RESULTS: Twenty-eight of all cultures taken in the ABP-received period (18.2%) and 25 (16.2%) of the ABP-discontinued cultures were considered to be indicative of symptomatic UTIs (P = 0.65). The multiple antibiotic resistance rate of microorganisms in cultures taken during the ABP-discontinued period (47; 30.5%) was lower than that in those taken in the ABP-received period (62; 40.3%), (P = 0.07). There was no difference between the ABP-received and ABP-discontinued periods with respect to the development of new lesions according to dimercaptosuccinic acid results (P = 0.14). CONCLUSION: Routine ABP usage is not protective against the development of symptomatic UTIs and new lesions in neurogenic bladder patients receiving CIC. Furthermore, the growth of resistant microorganisms increased in the ABP-received period.

Histopathological and ultrastructural effects of Losartan on embryonic rat kidney.

The aim of our study was to investigate the histopathological, immunohistochemical and ultrastructural effects of Losartan (a selective angiotensin II type-1 receptor blocker) on renal development in rats. Twelve pregnant rats were divided into control and experimental groups. In the experimental group, Losartan (10 mg/kg/day) was given via nasogastric tube, between the sixth day of implantation and time of sacrifice on embryonic days 18 and 20. All formalin-fixed, paraffin wax-embedded renal tissue sections were stained with hematoxylin and eosin or labelled for binding of primary antibodies against transforming growth factor-beta (TGF-beta 1,-2,-3) using an avidin-biotin-peroxidase method. For electron microscopic examination, samples were fixed with glutaraldehyde and osmium tetroxide and embedded in araldite. Glomerular basement membrane (GBM) thickness was measured and compared using an unpaired t-test. Angiotensin II type-1 receptor antagonism by Losartan inhibited renal growth and delayed nephron maturation. Increased immunoreactivity of TGF-beta's was observed in developing nephron precursors and interstitial cells in the experimental group. Electron microscopical examination showed that thickening of the GBM was normal in the control group but an irregular thickening was seen in the experimental group (p < 0.001). It was also seen that epithelial cells of developing tubules underwent apoptosis in the experimental group. Thus, renal development in rats seems to depend on an intact renin-angiotensin system.

Prevalence of urinary incontinence and lower urinary tract symptoms in school-age children.

PURPOSE: To investigate the prevalence of lower urinary tract symptoms (LUTS) and urinary incontinence (UI) in elementary school aged children in Manisa. MATERIALS AND METHODS: Dysfunctional Voiding and Incontinence Scoring System (DVIS) which was developed in Turkey is used. A total of 416 children, 216 (51.9%) male and 200 (48.1%) female were recruited in this study. RESULTS: Mean age of children was 10.35 ± 2.44 years (median10 years). Daytime UI frequency was 6.7% (28 child), nocturnal incontinence 16.6% (69 child) and combined daytime and nocturnal incontinence 4.1% (17 child). There was no statistically significant difference in the prevalence of nocturnal and or daytime UI between male and female gender. Mean DVIS score was 2.65 ± 3.95 and gender did not affect total DVIS points. The mean ages of achieving daytime bowel and bladder control were all significantly correlated with DVIS points. DVIS points were positively correlated with the history of UI of the family. Total points were increased when the father was unemployed. CONCLUSION: UI negatively influences health related quality of life of the family and child, so it is important that awareness of the UI and symptoms of lower urinary tract dysfunction.

Molecular characterization of cystinuria in south-eastern European countries.

Cystinuria is an autosomal recessive disorder caused by defective transport of cystine and dibasic amino acids in the proximal renal tubules and small intestine. So far, more than 128 mutations in SLC3A1 gene, and 93 in SLC7A9 gene have been described as a cause of cystinuria. We present a molecular characterization of the cystinuria in 47 unrelated south-east European families. The molecular methodology included direct sequencing, single strand conformational polymorphism, and restriction fragment length polymorphism. A total of 93 (94.9 %) out of 98 unrelated cystinuric chromosomes have been characterized. Mutations in SLC3A1 gene account for 64.3 % and in SLC7A9 gene for 30.6 % of the cystinuric chromosomes. Ten different mutations in SLC3A1 gene were found, and two of them were novel (C242R and L573X), while in SLC7A9 gene seven mutations were found, of which three were novel (G73R, V375I and c.1048_1051delACTC). The most common mutations in this study were T216M (24.5 %), M467T (16.3 %) and R365L (11.2 %) in SLC3A1 and G105R (21.4 %) in SLC7A9 gene. A population specificity of cystinuria mutations was observed; T216M mutation was the only mutation present among Gypsies, G105R was the most common mutation among Albanians and Macedonians, and R365L among Serbs. The results of this study allowed introduction of rapid, simple and cost-effective genetic diagnosis of cystinuria that enables an early preventive care of affected patients and a prenatal diagnosis in affected families.

Hemolytic uremic syndrome outbreak in Turkey in 2011.

The aim of this retrospective multicenter study was to define the epidemiological and clinical features and prognostic factors of the first diarrhea-related hemolytic uremic syndrome (D+HUS) outbreak in Turkey in 2011. All pediatric nephrology centers in Turkey were asked about D+HUS patients via e-mail. Seventy D+HUS patients (median age: 5.7 years) participated. The seasonal peak was around the 7th, 8th and 9th months with 44 cases, centered in the east Marmara region. No causative agent could be identified. The rate of neurological complications and mortality was 21.4% and 4.2%, respectively. Eculizumab was used in four cases. Two of them had severe neurological complications despite plasma exchange. Elevated polymorphonuclear leukocyte count during hospital admission was the predictor of both severe disease and poor outcome. Duration of prodrome was the predictor of poor outcome (p<0.05). In conclusion, the median age of the affected children was greater than in the previous reports, while clinical features and outcome were similar.