MARIA JULIA CORREIA LIMA NEPOMUCENO ARAUJO
Projetos de Pesquisa
Unidades Organizacionais
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
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- 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
- 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, EliasBackground 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.
- 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, EliasBackground: 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.
- 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.
conferenceObject Which Induction Therapy Should Be Used in Kidney Transplants with Prolonged Cold Ischemia Time?(2012) ARAUJO, M. J. C. L. N.; ONUSIC, V. L.; BATTAINI, L. C.; BARBOSA, E.; NAHAS, W. C.; CASTRO, M. C. R.With the aim to retrospectively analyze the impact of different induction therapies on transplant results of non-sensitized, first, isolated, adult, deceased kidney transplants who were submitted to cold ischemia times (CIT) ≥ 24 hours, 51 patients treated with Basiliximab (GI) were compared to 81 patients treated with Thymoglobulin (GII). Transplants were performed between Jan/2007 and July/2011. Maintenance longterm immunosuppression consisted of Tacrolimus, Mycophenolate and Prednisone in both groups. Patients treated with Thymoglobulin received CMV prophylaxis for 3 months with Gancyclovir. Demographic data are summarized in Table I. No differences were detected on recipient age and gender and brain death cause. Time on dialysis pre transplantation, donor age, donor Scr and CIT time were higher in GII. Follow-up time was longer in GI. Results were not different, except for CMV disease and are shown on Table II. Figure 1 shows the evolution of Scr over the 1st year in both groups. Demographic data GI (N= 51 ) GII (N= 81 ) p Recipient gender (M/F) 31/20 51/30 NS Recipient age (y) 49.9 49.6 NS Stroke as brain death cause (%) 64 62 NS Time on dialysis pre Tx (m) 85 184 0.02* Donor age (y) 47 53 0.02* CIT (hours) 26 28 0.01* Donor Scr (mg/dl) 1.4 1.8 0.02* * p< 0.05 Results GI (N= 51 ) GII (N= 81 ) p DGF rate (%) 67 63 NS Number of days at 1st hospitalization 19 18 NS Hospital readmission rate 0.7 (1.5/pt) 0.7 (1.4/pt) NS cute rejection rate (% ) 19 11 NS Acute rejection rate (% ) CMV rate (%) 27 13 0.04* 1y patient Survival 83 83 NS 1y graft Survival 81 79 NS * p< 0.05 In our center, patients who received kidneys with long ischemia time presented extremely high DGF rates and an impact on renal function at one year was observed. In this cohort, recipients treated with Thymoglobulin received more frequently kidneys from marginal donors with longer CIT, but the use of Thymoglobulin provided similar one year patient and graft survival and a tendency to lower acute rejection rates in these patients.- Biopsy vs. peripheral computed tomography to assess bone disease in CKD patients on dialysis: differences and similarities(2017) MARQUES, I. D. B.; ARAUJO, M. J. C. L. N.; GRACIOLLI, F. G.; REIS, L. M. dos; PEREIRA, R. M.; CUSTODIO, M. R.; JORGETTI, V.; ELIAS, R. M.; DAVID-NETO, E.; MOYSES, R. M. A.Results from bone biopsy and high-resolution peripheral quantitative computed tomography (HR-pQCT) were compared in 31 CKD patients. There was an agreement mainly for cortical compartment that may represent a perspective on the fracture risk assessment. HR-pQCT also provided some clues on the turnover status, which warrants further studies. Chronic kidney disease (CKD) patients are at high risk of bone disease. Although bone biopsy is considered the best method to evaluate bone disease, it is expensive and not always available. Here we have compared, for the first time, data obtained from bone biopsy and HR-pQCT in a sample of CKD patients on dialysis. HR-pQCT and dual-energy X-ray absorptiometry (DXA) were performed in 31 CKD patients (30 on dialysis). Biopsies were analyzed by quantitative histomorphometry, and classified according to TMV. We have found an inverse correlation between radius cortical density measured by HR-pQCT, with serum, as well as histomorphometric bone remodeling markers. Trabecular density and BV/TV measured through HR-pQCT in the distal radius correlated with trabecular and mineralized trabecular bone volume. Trabecular number, separation, and thickness obtained from HR-pQCT and from bone biopsy correlated with each other. Patients with cortical porosity on bone histomorphometry presented lower cortical density at the distal radius. Cortical density at radius was higher while bone alkaline phosphatase was lower in patients with low turnover. Combined, these parameters could identify the turnover status better than individually. There was an agreement between HR-pQCT and bone biopsy parameters, particularly in cortical compartment, which may point to a new perspective on the fracture risk assessment for CKD patients. Besides classical bone resorption markers, HR-pQCT provided some clues on the turnover status by measurements of cortical density at radius, although the significance of this finding warrants further studies.
- The pitfall of treating low bone turnover: Effects on cortical porosity(2016) ARAUJO, Maria Julia C. L. N.; KAROHL, Cristina; ELIAS, Rosilene M.; BARRETO, Fellype C.; BARRETO, Daniela Veit; CANZIANI, Maria Eugenia F.; CARVALHO, Aluizio B.; JORGETTI, Vanda; MOYSES, Rosa M. A.Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton, little is known about this compartment from bone biopsy studies, particularly in CKD patients. In addition, there is no prospective data on the effects of CKD-MBD therapy on cortical porosity (Ct.Po). This is a post hoc analysis on data from a randomized controlled trial on the effects of different phosphate binders on bone remodelling. Therapy was adjusted according to the first biopsy, and included sevelamer or calcium acetate, calcitriol and changes in calcium dialysate concentration. We measured Ct.Po at baseline and one year after. Fifty-two patients (46 +/- 13 years old, 67% women and 60% white) were enrolled. Ct.Po was already high at baseline in 85% of patients [30% (17, 46)1 and correlated with PTH (p = 0.001). Low bone turnover was seen in 28 patients (54.9%). After one-year treatment, PTH increased in patients with low turnover, as intended. However, increased Ct.Po was seen in 49 patients (94%). This increase correlated with the delta of phosphate (p = 0.015) and the delta of PTH (p = 0.03); it was also higher among non-white patients than in white patients (p = 0.039). The risk of increase in Ct.Po was 4.5 higher among non-white patients. Adjusted multiple regression analysis showed that the delta of Ct.Po was dependent on delta PTH and race (r(2) = 0.193). We concluded that in an attempt to increase bone turnover, the increase in PTH levels might be associated with higher cortical porosity, particularly in non-white patients. Whether this finding leads to a high risk of fracture deserves further investigation.
conferenceObject Which Induction Therapy Should Be Used in Kidney Transplants with Prolonged Cold Ischemia Time?(2012) ARAUJO, M. J. C. L. N.; ONUSIC, V. L.; BATTAINI, L. C.; BARBOSA, E. A.; BOJIKIAN, R. T.; DAVID, D. R.; ANTONOPOULOS, I. M.; PAULA, F. Jota de; NAHAS, W. C.; NETO, E. D.; LEMOS, F. B. C.; CASTRO, M. C. Ribeiro de- 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, VandaPurpose 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.
- Is parathyroidectomy always good for the heart?(2015) ARAUJO, Maria Julia C. L. N.; ELIAS, Rosilene M.; MOYSES, Rosa M. A.