RESUMO
Recombinant human growth hormone (GH) therapy has been shown to be effective in the treatment of growth failure related to growth hormone resistance among children with chronic renal failure. The traditional route of administration is subcutaneous injection. This study was designed to evaluate the effectiveness and tolerability of intraperitoneal (i.p.) administration of GH in prepubertal peritoneal dialysis patients. Nine subjects were enrolled. Eight completed 24 months of therapy with GH. Baseline height standard deviation scores (SDS) and growth velocity for the prior year were used for comparison. Peak serum GH was achieved 4 h after administration and serum half-life was 4.6 h. Mean height SDS was -3.1 at baseline, -2.5 at 1 year, and -2.3 at 2 years (NS) of GH therapy. Mean height velocity increased from a baseline of 4.6 cm/yr to 8.5 cm/yr in year 1 (P < 0.05) and 6.1 cm/yr in year 2 (NS) of i.p. GH therapy. Peritonitis infection rates were not increased from overall center rates. This research suggests that the intraperitoneal route of administration of GH can be utilized in the treatment of short stature among children requiring maintenance peritoneal dialysis therapy.
Assuntos
Hormônio do Crescimento Humano/administração & dosagem , Falência Renal Crônica/tratamento farmacológico , Adolescente , Criança , Desenvolvimento Infantil , Pré-Escolar , Feminino , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/farmacocinética , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Injeções Intraperitoneais , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Masculino , Estado Nutricional , Diálise Peritoneal , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico , SegurançaRESUMO
Denys-Drash syndrome is a rare human condition in which severe urogenital aberrations result in renal failure, pseudohermaphroditism, and Wilms' tumor (nephroblastoma). To investigate its possible role, we have analyzed the coding exons of the Wilms' tumor suppressor gene (WT1) for germline mutations. In ten independent cases of Denys-Drash syndrome, point mutations in the zinc finger domains of one WT1 gene copy were found. Nine of these mutations are found within exon 9 (zinc finger III); the remaining mutation is in exon 8 (zinc finger II). These mutations directly affect DNA sequence recognition. In two families analyzed, the mutations were shown to arise de novo. Wilms' tumors from three individuals and one juvenile granulosa cell tumor demonstrate reduction to homozygosity for the mutated WT1 allele. Our results provide evidence of a direct role for WT1 in Denys-Drash syndrome and thus urogenital system development.