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1.
Sci Rep ; 10(1): 16025, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994492

RESUMO

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (≤ 3 months; VEBNE) and early (4-15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ≤ 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort.


Assuntos
Nefrectomia/efeitos adversos , Doenças do Sistema Nervoso/epidemiologia , Rim Policístico Autossômico Recessivo/cirurgia , Diálise Renal/estatística & dados numéricos , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doenças do Sistema Nervoso/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
2.
Pediatr Transplant ; 20(4): 507-14, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27089840

RESUMO

In the pediatric population, little is known on de novo DSA development, its impact on graft function, and association with suboptimal IS. We assessed the prevalence of de novo DSA in the Vienna cohort of 40 renal transplanted children and adolescents and prospectively followed its association with clinical parameters, graft function, and proteinuria for one yr. At the cross-sectional analysis (median post-transplant time of five yr), 17% of the patients had developed de novo DSA. All HLA-Ab were anti-HLA class II antibodies and persisted in 85% of the cases until the follow-up screening performed within one yr. Basic clinical and laboratory parameters did not differ between DSA-negative and DSA-positive patients at the time of HLA-Ab screening. Suboptimal IS due to reduced medication or non-adherence could not be proven in DSA-positive patients. The changes in eGFR did not differ during the prospective study period, but there was a significantly higher proteinuria in the DSA-positive patients during the follow-up. Our data demonstrate an overall prevalence of 17% of de novo DSA in a pediatric renal transplant cohort. During 12 months of prospective follow-up time, we could demonstrate a significant impact of de novo DSA presence on proteinuria.


Assuntos
Antígenos HLA/imunologia , Isoanticorpos/imunologia , Transplante de Rim , Rim/fisiopatologia , Complicações Pós-Operatórias/imunologia , Proteinúria/imunologia , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Isoanticorpos/sangue , Rim/imunologia , Masculino , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Estudos Prospectivos , Proteinúria/sangue , Proteinúria/diagnóstico , Proteinúria/etiologia , Adulto Jovem
3.
Am J Physiol Renal Physiol ; 305(3): F277-85, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23698122

RESUMO

Calcimimetics are indicated for secondary hyperparathyroidism in chronic kidney disease, and some data have suggested their protective role for progression of renal damage. We aimed to evaluate whether a calcimimetic can slow the progression of kidney damage in uninephrectomized apolipoprotein E (ApoE)-deficient (ApoE-/-) mice. To this end, we compared its effect with that of calcitriol. Male ApoE-/- mice (12 wk old) were randomized to undergo sham operation (sham) or unilateral nephrectomy (UNX) and subsequently received the calcimimetic R-568 (4 µg·kg⁻¹·day⁻¹), calcitriol (0.03 µg·kg⁻¹·day⁻¹), or vehicle intraperitoneally. Glomerular number and volume, damage indexes (glomerular, vascular, and interstitial), and glomerular (podocytes, mesangial, and endothelial) cell number and volume were assessed in perfused kidneys after a 12-wk treatment period. Lower numbers of podocytes per glomerulus were observed in the UNX + vehicle group compared with the sham group, and this was prevented in the UNX + R-568 group but not in the UNX + calcitriol group. In parallel, albuminuria was higher in the untreated UNX group compared with the sham group, and the increase was prevented in the UNX + R-568 group. Interstitial fibrosis was more prevalent in the vehicle-treated UNX group compared with the sham group, and this was prevented in the UNX group treated with R-568 and less effectively with calcitriol treatment. In all UNX groups, the weight of the residual kidney was significantly higher compared with all sham groups. No differences were observed in serum ionized calcium and systolic blood pressure between the groups. The calcimimetic R-568 prevented interstial fibrosis and podocyte loss after uninephrectomy in ApoE-/- mice. Minor renal dysfunction, lack of secondary hyperparathyroidism, and hypertension in this model support the hypothesis of direct effects of this compound on glomerular cells.


Assuntos
Compostos de Anilina/farmacologia , Apolipoproteínas E/fisiologia , Nefropatias/patologia , Nefrectomia , Podócitos/efeitos dos fármacos , Albuminúria/metabolismo , Análise de Variância , Animais , Apolipoproteínas E/genética , Apoptose/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Cálcio/agonistas , Capilares/patologia , Imuno-Histoquímica , Nefropatias/genética , Glomérulos Renais/patologia , Masculino , Camundongos , Camundongos Knockout , Miocárdio/citologia , Tamanho do Órgão/efeitos dos fármacos , Fenetilaminas , Pletismografia , Podócitos/patologia , Propilaminas , Sistema Renina-Angiotensina/fisiologia , Vitamina D/farmacologia , Vitaminas/farmacologia
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