RESUMEN
BACKGROUND: Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder exhibiting a high risk for progressive chronic kidney disease (CKD). METHODS: This is a retrospective multicentre study of 25 paediatric cases with FHHNC in Poland. Median age at diagnosis was 4 years and median follow-up time was 4.8 years. RESULTS: All cases of FHHNC carried recessive mutations in CLDN16. The founder mutation in CLDN16, Leu151Phe, was the most frequent cause of FHHNC in Polish patients, with 13 (52%) cases being homozygous and 5 (20%) carrying Leu151Phe allele in compound heterozygosity. All cases showed nephrocalcinosis, increased urinary fractional excretion of magnesium and hypercalciuria. Other disease features included hypomagnesaemia (76%), hyperparathyroidism (76%), hyperuricaemia (56%) and hypocitraturia (60%). Treatment with thiazides effectively reduced hypercalciuria in most cases. During follow-up, renal function declined in 60% of patients; 12% of patients reached CKD stage 3 or 4 and one patient developed end-stage renal failure. CONCLUSIONS: We report one of the largest cohorts of FHHNC cases caused by CLDN16 mutations. A missense variant of CLDN16, Leu151Phe, is the most common mutation responsible for FHHNC in Poland. Additionally, we found that normomagnesaemia does not exclude FHHNC and the calculation of fractional excretion of Mg can be diagnostic in the setting of normomagnesaemia. We also demonstrate the efficacy of a treatment with thiazides in terms of hypercalciuria in the majority of patients.
Asunto(s)
Claudinas/genética , Hipercalciuria/genética , Mutación/genética , Nefrocalcinosis/genética , Defectos Congénitos del Transporte Tubular Renal/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Heterocigoto , Homocigoto , Humanos , Hipercalciuria/epidemiología , Lactante , Masculino , Nefrocalcinosis/epidemiología , Polonia/epidemiología , Prevalencia , Defectos Congénitos del Transporte Tubular Renal/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
Resistance to steroids and immunosuppression in pediatric nephrotic syndrome may be related to focal segmental glomeruloslerosis (FSGS). Rituximab, monoclonal anti-B-CD20-cell antibody is currently regarded as novel effective drug in selected cases. We describe the case of 8-years-old male pediatric patient, resistant to combined immunosuppression and presenting renal insufficiency (GFR 32.8 ml/min/1.73 m2). Patient was given overall 5 doses of rituximab [375 mg/m2/dose]. Nevertheless significant decrease of proteinuria, the further progress of renal disease was unaffected and patient developed end-stage renal failure. The efficacy of rituximab in nephrotic syndrome must be verified in controlled trials. Late onset of therapy in course of renal insufficiency might be the one of the reasons of treatment failure in our case.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Fallo Renal Crónico/etiología , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino , Antígenos CD20/inmunología , Niño , Preescolar , Resistencia a Medicamentos , Humanos , Masculino , Proteinuria/etiología , Proteinuria/prevención & control , RituximabRESUMEN
In this study a genetic determination of some cytokines synthesis is presented in group of 23 children with various kinds of nephrotic syndrome (NS). The gene polymorphisms of TNF-alpha, TGF-beta, IL-6, IL-10, INF-gamma were identified using PCR-SSP method combined with the measurement of levels of TNF-alpha, TGF-beta, IL-6, IL-10, INF-gamma synthesis. The differences in occurring frequency of high, middle and low genotypes TNF-alpha, TGF-beta and IL-6 synthesis between children with NS and control group were revealed. Significantly more frequently high TGF-beta and high IL-6 synthesis genotype in NS group were found. Because of high variability of cytokine level in blood in duration of NS and methodic difficulties of their measurement, identification of cytokines genes polymorphisms seems to be a method that can objectively describe the cytokine participation in NS pathophysiology.
Asunto(s)
Citocinas/genética , Síndrome Nefrótico/genética , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo Conformacional Retorcido-Simple , Adolescente , Niño , Femenino , Marcadores Genéticos/inmunología , Predisposición Genética a la Enfermedad , Humanos , Interferón gamma/genética , Interleucina-10/genética , Interleucina-6/genética , Masculino , Síndrome Nefrótico/inmunología , Factores de Riesgo , Factor de Crecimiento Transformador beta/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND: Nephrotic syndrome in children is commonly associated with dyslipidemia, which is considered a risk factor for endothelial dysfunction and atherosclerosis. Recently new markers of endothelial dysfunction, such as asymmetric dimethylarginine (ADMA), have gained importance. Another L-arginine derivative--symmetric dimethylarginine (SDMA)--may reflect the glomerular filtration rate (GFR). OBJECTIVES: The main aim of this study was to assess ADMA as a marker of atherosclerosis. Secondly, SDMA was examined for GFR assessment. MATERIAL AND METHODS: The study involved 32 children with nephrotic syndrome. Several parameters were examined in the remission and relapse phases of nephrotic syndrome, including ADMA, SDMA, cholesterol, triglycerides and GFR. RESULTS: In the relapse phase there was a negative correlation between ADMA and lipids (cholesterol and triglycerides). In both phases SDMA was negatively correlated with GFR. CONCLUSIONS: The role of ADMA as a marker for endothelial dysfunction is not significant. SDMA may be utilized to monitor GFR in children with nephrotic syndrome.