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No disponible
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Sociedades Médicas/organização & administração , Pediatria/tendências , Especialização/tendências , Planejamento Estratégico , Publicações Periódicas como Assunto/tendências , Afiliação Institucional/organização & administração , Avaliação Curricular das Faculdades de MedicinaRESUMO
The Sanger sequencing of patients with recessive polycystic kidney disease is challenging due to the length and heterogeneous mutational spectrum of the PKHD1 gene. Next generation sequencing (NGS) might thus be of special interest to search for PKHD1 mutations. The study involved a total of 22 patients with autosomal recessive polycystic kidney disease (ARPKD) and 8 parents of non-available ARPKD patients. Five pools of 6 samples each were sequenced with the Personal Genome Machine (PGM, Ion Torrent). For each DNA pool, a total of 109 fragments that covered the entire PKHD1 coding sequence were amplified in only two tubes followed by library preparation and NGS with the PGM. To validate the technique, each pool contained the DNA of at least one patient with known mutation. The putative mutations identified in each pool were confirmed and assigned to specific individuals through Sanger sequencing. All but one of the 109 amplicons were successfully read, and we identified the two PKHD1 mutations in 11 of the ARPKD cases, one mutation in 9 patients, and no mutation in only 2 patients. Six of the 8 parents from non-available patients were mutation carriers. The reported procedure would facilitate the large scale analysis of PKHD1 with a significant reduction in cost and labor.
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Sequenciamento de Nucleotídeos em Larga Escala/métodos , Doenças Renais Policísticas/genética , Receptores de Superfície Celular/genética , Análise de Sequência de DNA/métodos , Sequência de Bases , Feminino , Biblioteca Gênica , Humanos , Rim/patologia , Masculino , Mutação , Técnicas de Amplificação de Ácido Nucleico/métodosRESUMO
The health-related quality of life (HRQOL) of adolescents with end-stage renal disease (ESRD) is an important marker of disease burden. Our aims were to investigate HRQOL in a group of children and adolescents with ESRD and to compare them with the reference population norms. Ours was a cross-sectional study of 81 patients aged 10 years to 21 years with ESRD (68 with kidney transplants and 13 on dialysis) at five Spanish paediatric nephrology centres. HRQOL was investigated with the Spanish version of the child health and illness profile, adolescent edition (CHIP-AE). Clinical variables such as underlying diagnosis, number of rejection episodes, pre-emptive transplantation, anaemia and height were also analysed. No differences were found between patients with kidney transplants and their healthy peers in any domain or sub-domain of CHIP-AE. The group on dialysis scored lower than healthy controls and patients with transplants for satisfaction with health. Discomfort was higher in patients with transplants who had suffered one rejection episode. Physical discomfort was increased in anaemic patients with transplants. Short patients scored less in the satisfaction domain, with lower self-esteem and lower satisfaction with health. Adolescents with kidney transplants had better satisfaction with health than the group on dialysis, which matched the level of a healthy population. Further long-term prospective research is warranted.
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Falência Renal Crônica/terapia , Transplante de Rim , Qualidade de Vida , Diálise Renal , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Parameters allowing regular evaluation of renal function in a paediatric intensive care unit (PICU) are not optimal. The aim of the present study was to analyse the utility of serum cystatin C and beta2-microglobulin (B2M) in detecting decreased glomerular filtration rate in critically ill children. METHODS: This was a prospective, observational study set in an eight-bed PICU. Twenty-five children were included. The inverses of serum creatinine, cystatin C, and B2M were correlated with creatinine clearance (CrC) using a 24-hour urine sample and CrC estimation by Schwartz formula (Schwartz). The diagnostic value of serum creatinine, cystatin C, and B2M to identify a glomerular filtration rate under 80 ml/minute per 1.73 m(2) was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Mean age was 2.9 years (range, 0.1 to 13.9 years). CrC was less than 80 ml/minute per 1.73 m(2) in 14 children, and Schwartz was less than 80 ml/minute per 1.73 m(2) in 9 children. Correlations between inverse of B2M and CrC (r = 0.477) and between inverse of B2M and Schwartz (r = 0.697) were better than correlations between inverse of cystatin C and CrC (r = 0.390) or Schwartz (r = 0.586) and better than correlations between inverse of creatinine and CrC (r = 0.104) or Schwartz (r = 0.442). The ability of serum cystatin C and B2M to identify a CrC rate and a Schwartz CrC rate under 80 ml/minute per 1.73 m(2) was better than that of creatinine (areas under the ROC curve: 0.851 and 0.792 for cystatin C, 0.802 and 0.799 for B2M, and 0.633 and 0.625 for creatinine). CONCLUSION: Serum cystatin C and B2M were confirmed as easy and useful markers, better than serum creatinine, to detect acute kidney injury in critically ill children.
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Cistatinas/sangue , Taxa de Filtração Glomerular , Insuficiência Renal/sangue , Insuficiência Renal/diagnóstico , Microglobulina beta-2/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Creatinina/sangue , Creatinina/urina , Estado Terminal , Cistatina C , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Curva ROC , Insuficiência Renal/urinaRESUMO
Distal renal tubular acidosis (RTA) with nerve deafness is caused by mutations in the ATP6V1B1 gene causing defective function of the H+ -ATPase proton pump. We report five acidotic children (four males) from four unrelated families: blood pH 7.21-7.33, serum bicarbonate 10.8-14.7 mEq/l, minimum urinary pH 6.5-7.1 and fractional excretion of bicarbonate in the presence of normal bicarbonatemia 1.1-5.7%. Growth retardation and nephrocalcinosis, but not hypercalciuria, were common presenting manifestations. Hearing was normally preserved in one of the patients whose sister was severely deaf. One child was homozygous for a known mutation in exon 1: C>T (R31X). Three children were homozygous for a splicing mutation, intron 6 + 1G>A. The other patient was a compound heterozygote, having this mutation and a previously unreported mutation in exon 10: G>A (E330K). Our report shows that hearing loss is not always present in the syndrome of distal renal tubular acidosis with nerve deafness and the absence of hypercalciuria at diagnosis and describes a new mutation responsible for the disease in the ATP6V1B1 gene.
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Acidose Tubular Renal/genética , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/genética , Mutação , ATPases Vacuolares Próton-Translocadoras/genética , Acidose Tubular Renal/patologia , Acidose Tubular Renal/fisiopatologia , Pré-Escolar , Análise Mutacional de DNA , Feminino , Transtornos do Crescimento/genética , Transtornos do Crescimento/patologia , Transtornos do Crescimento/fisiopatologia , Perda Auditiva Neurossensorial/patologia , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Lactente , Masculino , Nefrocalcinose/genética , Nefrocalcinose/patologia , Nefrocalcinose/fisiopatologia , Reação em Cadeia da Polimerase , SíndromeRESUMO
AIM: To determine the role of tumor necrosis factor-alpha (TNF-alpha) gene polymorphism in promoting renal scarring among patients with vesicoureteric reflux (VUR). This genetic variant involves a guanosine to adenine transition at position -308, and this single-base polymorphism is associated with increased transcription of the TNF-alpha gene. Recent studies suggest that the TNF-alpha gene may be associated with predisposition to renal scarring. PATIENTS AND METHODS: A total of 195 (51.8% females) patients with VUR demonstrated by voiding cystourethrogram were recruited, 126 of them with reflux nephropathy diagnosed by dimercaptosuccinic scan. The control group included 266 healthy individuals. Genotyping was performed by polymerase chain reaction and digestion with a restriction enzyme. RESULTS: Allele frequencies of -308G and -308A were 83.8% and 16.2%, respectively in patients with VUR and 88.9% and 11.1%, respectively in controls (P<0.05). No differences were found in genotype distribution related to presence/absence of renal scars. There was no relationship between TNF-alpha genotype and grade of VUR or the presence of proteinuria. CONCLUSIONS: Our data suggest that the TNF-alpha AA genotype is not associated with reflux nephropathy. The TNF-alpha-308A allele could be related to a higher susceptibility to VUR.
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BACKGROUND: Hypertension is a risk factor for cardiovascular disease (CVD). Studies in adults have shown that high sensitivity C-reactive protein (CRP) levels are associated with increased risk of CVD and essential hypertension (EHT). Genetic background is widely accepted as a risk factor for CVD. The aim of the present study was to analyse the association of high sensitivity CRP levels with other cardiovascular risk factors in children and young adults with at least one parent with EHT. METHODS: Fifty one healthy children and young adults (28 boys) with at least one parent with hypertension and 69 (41 boys) whose parents did not have hypertension were recruited prospectively from primary care centres. High sensitivity CRP, fasting lipid profile, blood pressure (BP) and anthropometric variables were obtained for all participants. RESULTS: CRP values were higher in the study group than in controls (logCRP mean difference: -0.69; 95% confidence interval: -1.05 to -0.33), even when differences were adjusted for age, gender, body mass index (BMI) and triglyceride levels (p = 0.01). No differences were observed in BP values between groups. In the study group, 35.3% of the participants had a CRP level > or =1 mg/l compared to 14.5% in the control group (p = 0.009). CRP showed a significant correlation with body weight (rho = 0.28, p = 0.04), BMI (rho = 0.32; p = 0.02) and ponderosity index (rho = 0.28; p<0.05). CONCLUSIONS: CRP is significantly higher in the offspring of parents with EHT. A significant positive relationship exists between BMI and serum CRP levels in this high risk group of children and young adults.
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Proteína C-Reativa/análise , Hipertensão/genética , Adolescente , Adulto , Antropometria , Biomarcadores/sangue , Pressão Sanguínea/genética , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Hipertensão/sangue , Lipídeos/sangue , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
The purpose of this study was to investigate the relationship between salt taste perception and blood pressure (BP) in normotensive adolescents as modified by maternal fluid losses during the first trimester of gestation. Seventy-two healthy adolescents (42 boys) aged between 9.0-21.1 years, recruited from the population-based RICARDIN study, were included. A maternal questionnaire about the duration of pregnancy, birth weight and vomiting or diarrhoea in the first trimester of gestation was collected. The sample was categorized into: "vomiter descendents", those whose mother reported significant vomiting in the first trimester of gestation and "non-vomiter descendents" the remaining. Height, weight, and standardised BP measurement were recorded. Salt gustatory performance was assessed using a behavioral sensitivity test to determine the lower NaCl gustatory threshold, and a behavioral discrimination test, measuring the ability to distinguish among different saline solutions. Salt taste sensitivity showed a significant correlation with systolic BP (SBP) in "vomiter descendents" ( r = -0.66; P =0.003), but not in "non-vomiter descendents". Adjusted by gender, and actual height and weight, salt sensitivity performance remained significantly related to SBP. An association between descendents' SBP and maternal vomiting during gestation exists, adding a new element of evidence to the "Barker hypothesis".
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Pressão Sanguínea , Complicações na Gravidez/fisiopatologia , Cloreto de Sódio , Limiar Gustativo , Vômito/fisiopatologia , Adolescente , Peso Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Gravidez , Análise de Regressão , Índice de Gravidade de DoençaRESUMO
Kidney disease has not been considered a frequent complication in Down syndrome (DS) patients; a variety of urological abnormalities and glomerulopathies have been reported in this population, and some DS patients develop chronic renal failure (CRF). The aim of this study was to improve the understanding of renal disease in patients with DS, focusing on the incidence and range of kidney and urological abnormalities in a population of DS patients. A cross-sectional study was carried out in DS patients referred from a pediatric genetics unit of a tertiary care center. Medical records were reviewed. A 24-h urine specimen and a blood sample were obtained. Fractional excretion of sodium and potassium, tubular reabsorption of phosphate, urinary excretion of calcium, magnesium, uric acid, creatinine clearance and proteinuria were determined. Ultrasound was performed to evaluate the kidneys and the urinary tract. Laboratory data were reviewed for any possible renal disorder. Sixty-nine patients, aged 12 months to 24 years, were recruited. Pathological findings included three cases of voiding disturbances and a case of hypertension in a 7-year old girl. Eight patients (11.6%) had hyperuricemia without gout. Eighteen patients (24.2%) had hyperuricosuria. Urinalysis revealed three cases of mild proteinuria and two patients with microscopic hematuria. Minor radiological abnormalities were found in five patients (7.3%). Three patients (4.5%) had CRF. Renal disease in patients with DS is not as rare as previously thought, although the majority of findings are of minor relevance. According to the variety of pathologies, and in order to detect early irreversible renal injury, it seems quite reasonable to perform regular monitoring of renal function in these patients.
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Síndrome de Down/epidemiologia , Falência Renal Crônica/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Hiperuricemia/diagnóstico por imagem , Hiperuricemia/epidemiologia , Incidência , Lactente , Falência Renal Crônica/diagnóstico por imagem , Masculino , Proteinúria/diagnóstico por imagem , Proteinúria/epidemiologia , Ultrassonografia , Incontinência Urinária/diagnóstico por imagem , Incontinência Urinária/epidemiologiaRESUMO
BACKGROUND: Autosomal-recessive polycystic kidney disease (ARPKD) is an important neonatal nephropathy characterized by fusiform dilation of collecting ducts, congenital hepatic fibrosis, and in some cases Caroli's disease. The ARPKD gene, PKHD1, has recently been identified. Herein we describe an effective method for PKHD1 mutation screening and the results from analysis of a novel ARPKD cohort. METHODS: The coding region of PKHD1 was amplified as 79 fragments and analyzed for base pair changes by denaturing high-performance liquid chromatography (DHPLC). Forty-seven ARPKD and 14 pedigrees with congenital hepatic fibrosis and/or Caroli's disease, were screened for PKHD1 mutations. RESULTS: Thirty-three different mutations were detected on 57 alleles (51.1% ARPKD, 32.1% congenital hepatic fibrosis/Caroli's disease). In the 22 pedigrees where both mutations were identified, two were homozygous for 9689delA and the remainder were compound heterozygotes; a combination of truncating, missense and splicing changes. Patients with two truncating mutations all died in the perinatal period. Two frequent truncating mutations were identified: 9689delA (9 alleles) and 5896insA (8 alleles) plus some more common missense changes; haplotype analysis indicated most were ancestral mutations. CONCLUSION: DHPLC has been established as a rapid mutation screening method for ARPKD. The mutation detection rate was high in severely affected patients (85%), lower in those with moderate ARPKD (41.9%), and low, but significant, in adults with congenital hepatic fibrosis/Caroli's disease (32.1%). The prospects for gene-based diagnostics are complicated by the large gene size, marked allelic heterogeneity, and clinical diversity of the ARPKD phenotype. Identification of some common mutations, especially in specific populations, will aid mutation screening.
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Testes Genéticos/métodos , Rim Policístico Autossômico Recessivo/genética , Receptores de Superfície Celular/genética , Adolescente , Adulto , Pré-Escolar , Cromatografia Líquida de Alta Pressão/métodos , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Haplótipos , Humanos , Lactente , Recém-Nascido , Masculino , Mutação de Sentido Incorreto , LinhagemRESUMO
To investigate salt perception and discrimination and their possible association with blood pressure (BP), 72 healthy adolescents (42 boys) aged 9-21 years (mean 16.1 years) were studied. BP was measured with a standardized technique. Anthropometric measurement and conventional renal function tests were performed. Sensitivity tests to recognize the presence of salt when given simultaneously distilled/deionized water and a low sodium concentration water solution, and discrimination tests consisting of six graded samples of different saline solutions presented in randomized order were used to assess individual gustatory sensitivity. Average systolic BP values were 113.2+/-1.6 mmHg in boys and 109.6+/-1.9 mmHg in girls. Mean threshold level for salt sensitivity was 4.55+/-0.6 mmol/l. Systolic BP and salt sensitivity showed a significant correlation ( r=-0.33, P<0.01) even when adjusting for weight. Discrimination score was correlated with salt sensitivity ( r=0.27, P<0.05). There is a significant association between gustatory perception and BP in Spain adolescents, although a real cause-effect relationship has not been established.
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Pressão Sanguínea , Cloreto de Sódio na Dieta/farmacocinética , Limiar Gustativo/fisiologia , Adolescente , Adulto , Criança , Discriminação Psicológica/fisiologia , Feminino , Humanos , Rim/fisiologia , Masculino , Valores de ReferênciaRESUMO
The purpose of the study was to determine whether DNA polymorphisms at the renin-angiotensin-aldosterone (RAS) genes were associated with evolution to renal scar formation and, consequently, with reflux nephropathy (RN) in patients with vesicoureteral reflux (VUR). Some authors have suggested that the DD genotype of the angiotensin-converting enzyme (ACE) gene would be an adverse renal prognosis factor. We recruited 246 patients (aged 3 months to 22 years) from four Spanish hospitals. These included 69 patients with VUR, 110 with RN (determined by absence/presence of renal scarring on dimercaptosuccinc acid scan), 27 with chronic renal failure due to RN, and 40 patients (control group) with urinary tract infection and normal findings on renal ultrasonography and voiding cystoureterogram. The ACE I/D, angiotensin II type 1 receptor AT1 A1166C, angiotensin II type 2 receptor A3123C AT2, and angiotensinogen AGT M235T polymorphisms were determined on the basis of polymerase chain reaction amplification. ACE serum levels were determined by spectrophotometric methods. We found no statistical differences in the distribution of RAS polymorphisms between the different groups. The ACE D allele was linked to higher ACE serum levels. We found no association between ACE I/D polymorphism and presence of hypertension, proteinuria, grade of VUR, or unilateral/bilateral VUR. Patients with the DD genotype had a lower incidence of febrile urinary tract infection as a first symptom of VUR/RN (P<0.05). We conclude that genetic polymorphisms of RAS components are not independent prognostic indicators of renal scarring in patients with VUR.