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1.
Nephrol Dial Transplant ; 24(6): 1851-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19110485

RESUMO

BACKGROUND: Haemolytic uraemic syndrome (HUS) is a disorder characterized by thrombotic microangiopathy, which is caused in 'typical forms' by gastrointestinal infections with Escherichia Coli species that produce verotoxins. Several studies have identified negative prognostic factors of the disease, among which prolonged oliguria, neurological involvement and increased leukocytosis have been more consistently reported. We have hypothesized that the genetic background may also predispose to the development of typical forms of HUS and may influence the clinical course of the disease. METHODS: Fourteen polymorphisms, known to influence the coagulation pathway or the activity of the renin-angiotensin system, have been selected and studied in 150 Italian children with typical forms of HUS. Two hundred healthy Italian children were used as controls. RESULTS: The risk of developing HUS was strongly associated with the platelet glycoprotein 1balpha 145M allele (OR 3.08; CI: 1.62-5.85) (P < 0.001). A significant association was also found with polymorphisms located in the adipocyte-derived leucine aminopeptidase and factor V genes. A longer duration of dialysis was moderately associated with increased leukocytosis and with the 807T allele of the platelet glycoprotein 1a gene. High white blood cell count was also strongly associated with the risk of long-term sequelae (OR 2.91, CI: 1.21-6.98) (P < 0.02), whereas the 1166C allele of the angiotensin II type 1 receptor had a significant protective effect (OR 0.28, CI: 0.09-0.83) (P < 0.02). CONCLUSIONS: These results highlight the role of glycoprotein 1balpha in the physiopathology of typical forms of HUS and show that the genetic background plays a role in the susceptibility and severity of the disease.


Assuntos
Síndrome Hemolítico-Urêmica/genética , Adolescente , Alelos , Aminopeptidases/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Fator V/genética , Feminino , Predisposição Genética para Doença , Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/etiologia , Síndrome Hemolítico-Urêmica/terapia , Humanos , Lactente , Integrina alfa2/genética , Itália , Masculino , Glicoproteínas de Membrana , Proteínas de Membrana/genética , Antígenos de Histocompatibilidade Menor , Complexo Glicoproteico GPIb-IX de Plaquetas , Receptor Tipo 1 de Angiotensina/genética , Diálise Renal , Fatores de Risco , Escherichia coli Shiga Toxigênica/patogenicidade
2.
Am J Kidney Dis ; 50(3): 441-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17720523

RESUMO

BACKGROUND: Bone alterations in young renal transplant recipients were investigated in several studies with conflicting results. Quantitative ultrasound of the phalanges is a recently developed noninvasive procedure to assess skeletal status. STUDY DESIGN: Cross-sectional study at a single transplant center with values compared with previously studied healthy controls. SETTINGS & PARTICIPANTS: 40 children and young adult recipients of renal grafts (15 females, 25 males; age, 20.0 +/- 8.4 years) studied 7.1 +/- 3.8 years after kidney transplantation. PREDICTOR: Clinical, biochemical, and therapeutic features, including calcium, phosphate, and intact parathormone levels; and cumulative dosages of glucocorticoids and cyclosporine administered since transplantation. OUTCOME & MEASUREMENT: Phalangeal quantitative ultrasound, including amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT), mainly dependent on mineral density and cortical thickness, respectively. Age- and sex-matched healthy controls were used to provide age-related z scores; sex- and height-matched healthy subjects, to provide z scores related to statural age. RESULTS: Mean z scores of AD-SoS and BTT were -0.05 +/- 1.59 and -0.54 +/- 1.17, respectively (P > 0.05 and P < 0.001, respectively). Multivariate analysis showed that AD-SoS z score was associated significantly with body mass index, intact parathormone level, cumulative glucocorticoids administered in the first posttransplantation year, and cyclosporine administered since transplantation (model r(2) = 0.79; P < 0.001); BTT z score was associated significantly with glucocorticoid dosage in the first posttransplantation year and age (model r(2) = 0.55; P < 0.001). LIMITATIONS: Absence of other measures of bone structure and longitudinal measures and comparison to a noncurrent control group. CONCLUSIONS: Children and young adults may have decreased cortical thickness with maintained overall mineral density after renal transplantation. The findings of phalangeal quantitative ultrasound parallel observations using other imaging techniques. Phalangeal quantitative ultrasound may be a useful method to assess bone alternations after renal transplantation.


Assuntos
Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/etiologia , Falanges dos Dedos da Mão/diagnóstico por imagem , Transplante de Rim/efeitos adversos , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Ultrassonografia
4.
Pediatr Nephrol ; 18(12): 1229-35, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14593522

RESUMO

Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.


Assuntos
Síndrome Hemolítico-Urêmica/epidemiologia , Adolescente , Idade de Início , Doenças do Sistema Nervoso Central/complicações , Criança , Pré-Escolar , Estudos de Coortes , Diarreia/epidemiologia , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/metabolismo , Feminino , Síndrome Hemolítico-Urêmica/patologia , Humanos , Lactente , Itália/epidemiologia , Contagem de Leucócitos , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Toxina Shiga/metabolismo , Análise de Sobrevida , Resultado do Tratamento
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