MARIA JULIA CORREIA LIMA NEPOMUCENO ARAUJO

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LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina

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  • conferenceObject
    EVALUATION OF BONE MICROARCHITECTURE BY HIGH-RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY IN PATIENTS WITH CHRONIC KIDNEY DISEASE: COMPARISON WITH TRANSILIAC BONE BIOPSY
    (2015) MARQUES, Igor; ARAUJO, Maria Julia; GRACIOLLI, Fabiana; REIS, Luciene dos; CUSTODIO, Melani; PEREIRA, Rosa; JAMAL, Sophie; JORGETTI, Vanda; DAVID-NETO, Elias; MOYSES, Rosa
  • article 38 Citação(ões) na Scopus
    A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney Transplantation
    (2019) MARQUES, Igor Denizarde Bacelar; ARAUJO, Maria Julia Correia Lima Nepomuceno; GRACIOLLI, Fabiana Giorgetti; REIS, Luciene Machado dos; PEREIRA, Rosa Maria R.; ALVARENGA, Jackeline C.; CUSTODIO, Melani Ribeiro; JORGETTI, Vanda; ELIAS, Rosilene Motta; MOYSES, Rosa Maria Affonso; DAVID-NETO, Elias
    Background Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD). Methods In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. We used dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone biopsies to evaluate changes in bone in the 32 evaluable participants between the time of KTx and 12 months post-transplant. Results Both groups of patients experienced decreased bone turnover after KTx, but zoledronate itself did not affect this outcome. Unlike previous studies, DXA showed no post-transplant bone loss in either group; we instead observed an increase of bone mineral density in both lumbar spine and total hip sites, with a significant positive effect of zoledronate. However, bone biopsies showed post-transplant impairment of trabecular connectivity (and no benefit from zoledronate); HR-pQCT detected trabecular bone loss at the peripheral skeleton, which zoledronate partially attenuated. Conclusions Current immunosuppressive regimens do not contribute to post-transplant central skeleton trabecular bone loss, and zoledronate does not induce ABD. Because fractures in transplant recipients are most commonly peripheral fractures, clinicians should consider bisphosphonate use in patients at high fracture risk who have evidence of significantly low bone mass at these sites at the time of KTx.
  • article 42 Citação(ões) na Scopus
    Persistent hyperparathyroidism as a risk factor for long-term graft failure: the need to discuss indication for parathyroidectomy
    (2018) ARAUJO, Maria Julia Correia Lima Nepomuceno; RAMALHO, Janaina Almeida Mota; ELIAS, Rosilene Motta; JORGETTI, Vanda; NAHAS, William; CUSTODIO, Melani; MOYSES, Rosa M. A.; DAVID-NETO, Elias
    Background: Although a successful kidney transplant (KTx) improves most of the mineral and bone disorders (MBD) produced by chronic kidney disease (CKD), hyperparathyroidism may persist (pHPT). Current guidelines recommend parathyroidectomy if serum parathormone is persistently elevated 1 year after KTx, because pHPT has been recently associated with poor graft outcomes. However, whether patients with pHPT and adequate renal function are at risk for long-term graft failure is unknown. Methods: Longitudinal follow-up of 911 adults submitted to KTx between January 2005 and December 2014, with estimated glomerular filtration rate (eGFR) >= 30 mL/min 1 year after surgery. Clinical and laboratory data were collected from electronic database. Graft failure was defined as return to dialysis. Results: Overall, 62% of the patients were classified as having pHPT 1 year after KTx. After a mean follow-up time of 47 months, there were 59 graft failures (49 in pHPT and 10 in non-pHPT group, P = .003). At last follow-up, death-censored graft survival was lower in the pHPT group (P = .009), even after adjustment for age at KTx, donor age, donor type, acute rejection, parathyroidectomy, and eGFR at 1 year after transplantation (odds ratio [OR] 1.99; 1.004-3.971; P = .049). A PTH of 150 pg/mL at 6 months was the best cutoff to predict pHPT at 1 year (specificity = 92.1%). Conclusion: Having pHPT after a successful KTx increases the long-term risk of death-censored graft failure. This result highlights the need for better recognition and management of CKD-MBD before and during the first year after KTx, and opens a discussion on the more appropriate timing to perform parathyroidectomy.
  • article 13 Citação(ões) na Scopus
    Comparison of serum levels with bone content and gene expression indicate a contradictory effect of kidney transplantation on sclerostin
    (2019) ARAUJO, Maria Julia Correia Lima Nepomuceno; MARQUES, Igor Denizarde Bacelar; GRACIOLLI, Fabiana Giorgetti; FUKUHARA, Luzia; REIS, Luciene Machado dos; CUSTODIO, Melani; JORGETTI, Vanda; ELIAS, Rosilene Mota; DAVID-NETO, Elias; MOYSES, Rosa M. A.
    In an attempt to clarify the mechanisms of post-transplant bone disease we investigated the bone content and gene expression of several bone-related proteins. After a successful kidney transplant, the content of sclerostin in bone biopsies was found to be increased as measured by immunohistochemistry, multiplex assay, and gene expression despite a concomitant decrease of sclerostin in the serum. The phosphorylation of beta-catenin was increased, confirming Wnt pathway inhibition, an effect accompanied by an increase of the receptor activator of nuclear factor kappa-B ligand (RANKL) and a decrease of osteoprotegerin protein levels in both serum and bone. Thus, changes in circulating biomarkers after kidney transplantation cannot be easily extrapolated to concomitant changes occurring in the bone. Hence, overall treatment decisions post kidney transplant should not be based on serum biochemistry alone.
  • article 3 Citação(ões) na Scopus
    The effect of vitamin D and zoledronic acid in bone marrow adiposity in kidney transplant patients: A post hoc analysis
    (2018) HERNANDEZ, Mariel J.; REIS, Luciene M. dos; MARQUES, Igor D.; ARAUJO, Maria J.; TRUYTS, Cesar A. M.; OLIVEIRA, Ivone B.; BARRETO, Fellype C.; DAVID-NETO, Elias; CUSTODIO, Melani R.; MOYSES, Rosa M.; BELLORIN-FONT, Ezequiel; JORGETTI, Vanda
    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-adonor 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.