Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Pediatr Nephrol ; 39(6): 1847-1858, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38196016

RESUMO

BACKGROUND: We aimed to develop a tool for predicting HNF1B mutations in children with congenital abnormalities of the kidneys and urinary tract (CAKUT). METHODS: The clinical and laboratory data from 234 children and young adults with known HNF1B mutation status were collected and analyzed retrospectively. All subjects were randomly divided into a training (70%) and a validation set (30%). A random forest model was constructed to predict HNF1B mutations. The recursive feature elimination algorithm was used for feature selection for the model, and receiver operating characteristic curve statistics was used to verify its predictive effect. RESULTS: A total of 213 patients were analyzed, including HNF1B-positive (mut + , n = 109) and HNF1B-negative (mut - , n = 104) subjects. The majority of patients had mild chronic kidney disease. Kidney phenotype was similar between groups, but bilateral kidney anomalies were more frequent in the mut + group. Hypomagnesemia and hypermagnesuria were the most common abnormalities in mut + patients and were highly selective of HNF1B. Hypomagnesemia based on age-appropriate norms had a better discriminatory value than the age-independent cutoff of 0.7 mmol/l. Pancreatic anomalies were almost exclusively found in mut + patients. No subjects had hypokalemia; the mean serum potassium level was lower in the HNF1B cohort. The abovementioned, discriminative parameters were selected for the model, which showed a good performance (area under the curve: 0.85; sensitivity of 93.67%, specificity of 73.57%). A corresponding calculator was developed for use and validation. CONCLUSIONS: This study developed a simple tool for predicting HNF1B mutations in children and young adults with CAKUT.


Assuntos
Nefropatias , Sistema Urinário , Anormalidades Urogenitais , Refluxo Vesicoureteral , Criança , Humanos , Adulto Jovem , Estudos Retrospectivos , Rim/anormalidades , Sistema Urinário/anormalidades , Mutação , Nefropatias/genética , Magnésio , Fator 1-beta Nuclear de Hepatócito/genética
2.
Pediatr Nephrol ; 35(10): 1877-1886, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32388583

RESUMO

BACKGROUND: Hypomagnesemia in patients with congenital anomalies of the kidneys and urinary tract or autosomal dominant tubulointerstitial kidney disease is highly suggestive of HNF1B-associated disease. Intriguingly, the frequency of low serum Mg2+ (sMg) level varies and is lower in children than in adults with HNF1B mutations that could be partially due to application of inaccurate normal limit of sMg, irrespective of age and gender. We aimed to re-assess cross-sectionally and longitudinally the frequency of hypomagnesemia in HNF1B disease by using locally derived reference values of sMg. METHODS: Fourteen children with HNF1B-associated kidney disease were included. Control group comprising 110 subjects served to generate 2.5th percentiles of sMg as the lower limits of normal. RESULTS: In both controls and patients, sMg correlated with age, gender, and fractional excretion of Mg2+. In girls, sMg concentration was higher than in boys when analyzed in the entire age spectrum (p < 0.05). In HNF1B patients, mean sMg was lower than in controls as compared with respective gender- and age-specific interval (p < 0.001). Low sMg levels (< 0.7 mmol/l) were found in 21.4% of patients at diagnosis and 36.4% at last visit, which rose to 85.7% and 72.7% respectively when using the age- and gender-adjusted reference data. Similarly, in the longitudinal observation, 23% of sMg measurements were < 0.7 mmol/l versus 79.7% when applying respective references. CONCLUSIONS: Hypomagnesemia is underdiagnosed in children with HNF1B disease. sMg levels are age- and gender-dependent; thus, the use of appropriate reference data is crucial to hypomagnesemia in children.


Assuntos
Fator 1-beta Nuclear de Hepatócito/genética , Magnésio/sangue , Nefrite Intersticial/sangue , Anormalidades Urogenitais/sangue , Refluxo Vesicoureteral/sangue , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos Transversais , Análise Mutacional de DNA , Feminino , Humanos , Rim/metabolismo , Estudos Longitudinais , Masculino , Mutação , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/genética , Valores de Referência , Reabsorção Renal/genética , Estudos Retrospectivos , Fatores Sexuais , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/genética , Refluxo Vesicoureteral/diagnóstico , Refluxo Vesicoureteral/genética
3.
Nephrol Dial Transplant ; 33(1): 85-94, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27708066

RESUMO

Background: Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated with mutations in the OCRL gene and characterized by progressive chronic kidney disease (CKD). Here, we aimed to investigate the long-term renal outcome and identify potential determinants of CKD and its progression in children with these tubulopathies. Methods: Retrospective analyses were conducted of clinical and genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype-phenotype analysis, we grouped mutations according to their type and localization. To investigate progression of CKD we used survival analysis by Kaplan-Meier method using stage 3 CKD as the end-point. Results: Median estimated glomerular filtration rate (eGFR) was lower in the LS group compared with DD2 (58.8 versus 87.4 mL/min/1.73 m2, P < 0.01). CKD stage II-V was found in 82% of patients, of these 58% and 28% had moderate-to-severe CKD in LS and DD2, respectively. Three patients (3%), all with LS, developed stage 5 of CKD. Survival analysis showed that LS was also associated with a faster CKD progression than DD2 (P < 0.01). On multivariate analysis, eGFR was dependent only on age (b = -0.46, P < 0.001). Localization, but not type of mutations, tended to correlate with eGFR. There was also no significant association between presence of nephrocalcinosis, hypercalciuria, proteinuria and number of adverse clinical events and CKD. Conclusions: CKD is commonly found in children with OCRL mutations. CKD progression was strongly related to the underlying diagnosis but did not associate with clinical parameters, such as nephrocalcinosis or proteinuria.


Assuntos
Hipercalciúria/epidemiologia , Mutação , Nefrocalcinose/epidemiologia , Monoéster Fosfórico Hidrolases/genética , Proteinúria/epidemiologia , Insuficiência Renal Crônica/genética , Adolescente , Criança , Pré-Escolar , Progressão da Doença , Feminino , Genótipo , Taxa de Filtração Glomerular , Humanos , Hipercalciúria/genética , Masculino , Nefrocalcinose/genética , Fenótipo , Proteinúria/genética , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Resultado do Tratamento
4.
Am J Case Rep ; 22: e928994, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33526762

RESUMO

BACKGROUND Maturity onset diabetes of the young (MODY) usually presents in patients under the age of 25 years and is an autosomal dominant condition associated with mutations in the hepatocyte nuclear factor 1 alpha gene, glucokinase gene, or hepatocyte nuclear factor 4 alpha gene. This report is of a series of 4 cases from Poland of MODY type 5 associated with mutations in the hepatocyte nuclear factor 1 beta (HNF1B) gene, including a 13-year-old boy and adult men aged 33, 34, and 35 years. CASE REPORT Three cases were diagnosed late, in patients in their mid-thirties. In two patients, the initial presentation was symptomatic diabetes complicated by ketoacidosis and hyperglycemic hyperosmolar state. Renal cysts were found in all patients, and pancreatic hypoplasia in 3 patients. All patients except 1 were negative for autoantibodies; 1 presented with hypomagnesemia. Insulin therapy was instituted in all cases. The combination of family history, imaging study results, and biochemical characteristics led to the decision to perform genetic analysis, which was conducted in 2 cases at diagnosis, and in the 2 remaining patients at 1 month and 2 years after diagnosis, respectively. Follow-up data revealed hypomagnesemia and/or hypermagnesuria in all patients. CONCLUSIONS We present 3 young men over 25 years and 1 boy with HNF1B-MODY. Although rare, autosomal dominant gene associations should be considered in young patients with diabetes who present with renal/pancreatic anomalies and low serum magnesium. Unusual presentation and the presence of autoantibodies should not eliminate the possibility of a HNF1B defect.


Assuntos
Diabetes Mellitus Tipo 2 , Fator 1-alfa Nuclear de Hepatócito , Adolescente , Adulto , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Masculino , Mutação , Polônia
5.
J Clin Med ; 10(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34362049

RESUMO

BACKGROUND: Hyperuricemia is recognized as an important feature of nephropathy, associated with a mutation in the hepatocyte nuclear factor-1B (HNF1B) gene, and could serve as a useful marker of the disease. However, neither a causal relationship nor its predictive value have been proven. The purpose of this study was to assess this in children with renal malformations, both with (mut+) and without HNF1B mutations (mut-). METHODS: We performed a retrospective analysis of clinical characteristics of pediatric patients tested for HNF1B mutations, collected in a national registry. RESULTS: 108 children were included in the study, comprising 43 mut+ patients and 65 mut- subjects. Mean sUA was higher and hyperuricemia more prevalent (42.5% vs. 15.4%) in HNF1B carriers. The two groups were similar with respect to respect to age, sex, anthropometric parameters, hypertension, and renal function. Renal function, fractional excretion of uric acid and parathyroid hormone level were independent predictors of sUA. The potential of hyperuricemia to predict mutation was low, and addition of hyperuricemia to a multivariate logistic regression model did not increase its accuracy. CONCLUSIONS: Hyperuricemia is an early and common feature of HNF1B nephropathy. A strong association of sUA with renal function and parathyroid hormone limits its utility as a reliable marker to predict HNF1B mutation among patients with kidney anomalies.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA