RESUMO
BACKGROUND: Intronic WT1 mutations are usually causative of Frasier syndrome with focal segmental glomerulosclerosis as the characteristic nephropathy. Membranoproliferative glomerulonephritis is not commonly associated with disorders of sex development but has been recently identified as a WT1-associated nephropathy, but usually in cases of exonic mutations in either isolated Wilms tumor or Denys-Drash syndrome. METHODS: The clinical and genetic data from 3 individuals are reported. RESULTS: This report describes the kidney manifestations in 3 individuals from 2 unrelated families with Frasier syndrome intronic WT1 mutations, noting that 2 of the 3 individuals have histologically confirmed membranoproliferative glomerulonephritis. CONCLUSIONS: These case reports support expansion of the clinical spectrum of the kidney phenotypes associated with Frasier syndrome providing evidence of an association between WT1 mutation and an immune complex-related membranoproliferative glomerulonephritis. A higher resolution version of the Graphical abstract is available as Supplementary information.
Assuntos
Síndrome de Denys-Drash , Glomerulonefrite Membranoproliferativa , Disgenesia Gonadal , Neoplasias Renais , Tumor de Wilms , Síndrome de Denys-Drash/genética , Síndrome de Denys-Drash/patologia , Síndrome de Frasier/genética , Genes do Tumor de Wilms , Glomerulonefrite Membranoproliferativa/genética , Disgenesia Gonadal/genética , Humanos , Neoplasias Renais/genética , Mutação , Proteínas WT1/genética , Tumor de Wilms/genéticaRESUMO
BACKGROUND: The effectiveness of rhGH on growth and final height (FH) was determined in children with CKD and kidney failure using data linkage from two national databases. METHODS: Data on Australian children with CKD and kidney failure treated with rhGH were obtained by linking ANZDATA and OzGrow registries. The CKD cohort included children treated with rhGH prior to kidney replacement therapy (KRT). The KRT cohort consisted of children with kidney failure, some received rhGH, and some were untreated. Height standard deviation scores (Ht-SDS) were calculated with final height defined as last height recorded in girls > 16 years of age and boys > 17 years of age. RESULTS: In the CKD group, there were 214 children treated with rhGH prior to KRT. In the KRT group, there were 1,032 children, 202 (19%) treated with rhGH and 830 (81%) untreated. Growth significantly improved in the rhGH-treated CKD group (ΔHt-SDS = +0.80 [+0.68 to +0.92]; p < 0.001) and the rhGH-treated KRT group (ΔHt-SDS = +0.38 [+0.27 to +0.50]; p < 0.001). Within the KRT cohort, final height was available for 423 patients (41%), of which 137 (32%) had been treated with rhGH. The rhGH-treated group demonstrated marginally better catch-up growth (ΔHt-SDS = +0.05 [-0.18 to 0.29]) compared to the non-rhGH-treated group (ΔHt-SDS = -0.03 [-0.16 to 0.10]; p = 0.49). CONCLUSIONS: This large linkage study confirms rhGH is effective in improving height in children with CKD pre-KRT. However, rhGH appears to have a variable impact on growth once children have commenced KRT resulting in a marginal impact on final height.
Assuntos
Hormônio do Crescimento Humano , Insuficiência Renal Crônica , Austrália/epidemiologia , Estatura , Criança , Feminino , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/etiologia , Hormônio do Crescimento , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
The late outcome in 55 children with infection-mediated haemolytic uremic syndrome (Shiga Toxin E Coli (STEC)-HUS and pneumococcal HUS) observed in 1979-1995 was followed up 23 years after disease onset. Of these, two were later confirmed to have atypical HUS (aHUS). Furthermore, of this population, five children had impaired kidney function at 3-months follow-up, which continued to deteriorate. These children had significant oliguria/anuria and hypertension during their illness requiring early dialysis and antihypertensive therapy. At 23 years post-disease onset, all five (100%) of these children have developed end-stage kidney disease or chronic kidney disease. Eculizumab is a monoclonal antibody that binds with high affinity to the C5 protein of the complement pathway, a major component of the pathophysiology of infection-mediated HUS. There are no long-term randomised controlled trials in the literature to support its use in such cases. Our 23-year follow-up of a population of severely affected children with infection-mediated HUS demonstrates a high percentage of chronic kidney disease and end-stage kidney disease (19%). Randomised controlled trials with eculizumab are now being conducted in this affected cohort.
