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1.
PLoS One ; 13(5): e0197994, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29799857

RESUMO

PURPOSE: Osteoblasts and adipocytes are derived from mesenchymal stem cells. An imbalance in the differentiation of these lineages could affect the preservation of bone integrity. Several studies have suggested the importance of this imbalance in the pathogenesis of osteoporosis after kidney transplant (KT), but the role of bone marrow adiposity in this process is not well known, and if the treatment with the anti-absorptive (zoledronic acid-ZA) drugs could attenuate bone loss. Thus, our objective was compare bone marrow adiposity, osteoblasts and osteocytes before and after KT, verify an association between bone remodeling process (Turnover, Volume, and Mineralization-TMV classification), the osteocyte sclerostin expression to evaluate if there is a role of Wnt pathway, as well as the effect of ZA on these cells. METHODS: We studied 29 new living-donor KT patients. One group received ZA at the time of KT plus cholecalciferol for twelve months, and the other group received only cholecalciferol. Bone biopsies were performed at baseline and after 12 months of treatment. Histomorphometric evaluation was performed in bone and bone marrow adipocytes. Sclerostin (Scl) expression in osteocytes was evaluated by immunohistochemistry. RESULTS: Some bone marrow adiposity parameters were increased before KT. After KT, some of them remained increased and they worsened with the use of ZA. In the baseline, lower bone Volume and Turnover, were associated with increased bone marrow adiposity parameters (some of them). After KT, both groups showed the same associations. Osteocyte Scl expression after KT decreased with the use of ZA. We observed also an inverse association between bone adiposity parameters and lower osteocyte sclerostin expression 12 months after KT. CONCLUSION: In conclusion, the present study suggests that KT fails to normalize bone marrow adiposity, and it even gets worse with the use of ZA. Moreover, bone marrow adiposity is inversely associated with bone Volume and Turnover, which seems to be accentuated by the antiresorptive therapy.


Assuntos
Adiposidade/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Difosfonatos/farmacologia , Imidazóis/farmacologia , Transplante de Rim , Vitamina D/farmacologia , Adulto , Medula Óssea/fisiologia , Remodelação Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Proteína 1 de Leucemia Linfocítica Aguda de Células T/metabolismo , Adulto Jovem , Ácido Zoledrônico
2.
Kidney Int ; 87(5): 1039-45, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25493951

RESUMO

Chronic kidney disease--mineral bone disorder (CKD-MBD) is a complex syndrome influenced by various factors, such as age, CKD etiology, uremic toxins, and dialysis modality. Although extensively studied in hemodialysis (HD) patients, only a few studies exist for peritoneal dialysis (PD) patients. Since most of these older studies contain no bone biopsy data, we studied the pattern of renal osteodystrophy in 41 prevalent PD patients. The most common presentation was adynamic bone disease (49%). There was a significant inverse association between serum sclerostin (a Wnt/ß-catenin pathway inhibitor that decreases osteoblast action and bone formation) and the bone formation rate. Bone alkaline phosphatase had the best sensitivity and specificity to detect both high- and low-turnover diseases. The comparison between nondiabetic PD and HD patients, matched by age, gender, parathyroid hormone level, and length of dialysis, revealed low 25-hydroxyvitamin D levels, worse bone mineralization, and low bone turnover in the nondiabetic PD group. Thus, adynamic bone disease was the most frequent type of renal osteodystrophy in PD patients. Sclerostin seems to participate in the pathophysiology of adynamic bone disease and bone alkaline phosphatase was the best serum marker of bone turnover in these patients.


Assuntos
Biomarcadores/sangue , Proteínas Morfogenéticas Ósseas/sangue , Remodelação Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Diálise Peritoneal , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Osso e Ossos/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Estudos Transversais , Feminino , Marcadores Genéticos , Humanos , Falência Renal Crônica/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Calcificação Vascular
3.
Clin Transplant ; 27(2): E169-76, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23351041

RESUMO

BACKGROUND: Among kidney transplant recipients (KTRs), tuberculosis is one of the most common opportunistic infections and is associated with high morbidity and mortality. The aim of this study was to describe the incidence, clinical features, and prognosis of tuberculosis in KTRs. METHODS: Retrospective single-center observational study involving all cases of tuberculosis in KTRs between 2000 and 2010. RESULTS: Of the 1549 KTRs evaluated, 43 (2.8%) developed tuberculosis, translating to an annual incidence of 803 cases/100 000 patients, considerably higher than that reported for the general population of Brazil. The median time to tuberculosis (TB) onset after transplantation was 196 d (range, 19-3626 d). Of the KTRs with tuberculosis, 67% became infected within the first year post-transplant, 74% had pulmonary tuberculosis, and 7% had a previous history of active tuberculosis. No tuberculosis prophylaxis was employed before or after transplantation. The most common symptoms were fever (in 79%), cough (in 35%), and dyspnea (in 16%). The median time from the onset of symptoms to the start of treatment was 28 d. The median duration of antituberculosis therapy was 196 d. In 15 patients (35%), the immunosuppressive therapy was reduced, and the incidence of acute rejection was higher in patients with tuberculosis than in those without (44% vs. 28%). Mortality during tuberculosis treatment was 12% (5 cases), and all five deaths were attributed to tuberculosis. Ten-yr death-censored graft survival and patient survival were similar between patients with tuberculosis and those without. CONCLUSION: Among KTRs, symptoms of tuberculosis are often attenuated, which leads to delayed diagnosis, and tuberculosis-related mortality remains high.


Assuntos
Transplante de Rim , Infecções Oportunistas/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Tuberculose/diagnóstico , Adulto , Antituberculosos/uso terapêutico , Brasil , Quimioterapia Combinada , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão/efeitos adversos , Incidência , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/etiologia , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/etiologia
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