MELANI RIBEIRO CUSTODIO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
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- The unexpected presence of iron in bone biopsies of hemodialysis patients(2018) CUSTODIO, Melani R.; ELIAS, Rosilene M.; VELASQUEZ, Wagner D.; REIS, Luciene M. dos; OLIVEIRA, Ivone B.; MOYSES, Rosa M. A.; CARVALHO, Aluizio B.; JORGETTI, VandaPurpose Bone biopsy defines classical diseases that constitute the renal osteodystrophy. There is a recent concern regarding other histological findings that are not appreciated by using the turnover, mineralization, and volume (TMV) classification. Iron (Fe) overload has been considered a new challenge and the real significance of the presence of this metal in bones is not completely elucidated. Therefore, the main goal of the current study was to not only to identify bone Fe, but also correlate its presence with demographic, and biochemical characteristics. Methods This is a cross-sectional analysis of bone biopsies performed in 604 patients on dialysis from 2010 to 2014 in a tertiary academic Hospital. Results Histomorphometric findings revealed the presence of Fe in 29.1%. Fe was associated with higher levels of serum ferritin and serum calcium. No TMV status was related to Fe bone overload. Conclusion Our study has highlighted that the presence of Fe in one-third of bone samples has unknown clinical significance. The lack of other contemporary bone biopsy study reporting Fe prevents us from comparison. The findings presented here should be specifically addressed in a future research and will require attention prior to implementation of any clinical guideline. If any proposed treatment, however, would change the bone Fe-related morbidity is undetermined.
- Chitosan-Fe (III) Complex as a Phosphate Chelator in Uraemic Rats: A Novel Treatment Option(2018) CARMO, Wander Barros do; CASTRO, Barbara Bruna Abreu; RODRIGUES, Clovis Antonio; CUSTODIO, Melani Ribeiro; SANDERS-PINHEIRO, HeladyPhosphate retention and hyperphosphataemia are associated with increased mortality in patients with chronic kidney disease (CKD). We tested the use of cross-linked iron chitosan III (CH-FeCl) as a potential phosphate chelator in rats with CKD. We evaluated 96 animals, divided equally into four groups (control, CKD, CH-FeCl and CKD/CH-FeCl), over 7 weeks. We induced CKD by feeding animals an adenine-enriched diet (0.75% in the first 4 weeks and 0.1% in the following 3 weeks). We administered 30 mg/kg daily of the test polymer, by gavage, from the third week until the end of the study. All animals received a diet supplemented with 1% phosphorus. Uraemia was confirmed by the increase in serum creatinine in week 4 (36.24 +/- 18.56 versus 144.98 +/- 22.1 mol/L; p = 0.0001) and week 7 (41.55 +/- 22.1 versus 83.98 +/- 18.56 mol/L; p = 0.001) in CKD animals. Rats from the CKD group treated with CH-FeCl had a 54.5% reduction in serum phosphate (6.10 +/- 2.23 versus 2.78 +/- 0.55 mmol/L) compared to a reduction of 25.6% in the untreated CKD group (4.75 +/- 1.45 versus 3.52 +/- 0.74 mmol/L, p = 0.021), between week 4 and week 7. At week 7, renal function in both CKD groups was similar (serum creatinine: 83.98 +/- 18.56 versus 83.10 +/- 23.87 mol/L, p = 0.888); however, the CH-FeCl-treated rats had a reduction in phosphate overload measured by fractional phosphate excretion (FEPi) (0.71 +/- 0.2 versus 0.4 +/- 0.16, p = 0.006) compared to the untreated CKD group. Our study demonstrated that CH-FeCl had an efficient chelating action on phosphate.
- 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.
- Quality of life after surgery in secondary hyperparathyroidism, comparing subtotal parathyroidectomy with total parathyroidectomy with immediate parathyroid autograft: Prospective randomized trial(2018) ALVES FILHO, Wellington; PLAS, Willemijn Y. van der; BRESCIA, Marilia D. G.; NASCIMENTO JR., Climerio R.; GOLDENSTEIN, Patricia T.; MASSONI NETO, Ledo M.; ARAP, Sergio S.; CUSTODIO, Melani R.; BUENO, Rodrigo O.; MOYSES, Rosa M. A.; JORGETTI, Vanda; KRUIJF, Schelto; MONTENEGRO, Fabio L. M.Background: No prospective randomized data exist about the impact of various strategies of parathyroidectomy in secondary hyperparathyroidism patients on quality of life and its possible relationship with metabolic status after the operation. Method: In a prospective randomized trial, the Short Form 36 Health Survey Questionnaire was applied to 69 patients undergoing parathyroidectomy through various approaches: subtotal parathyroidectomy (n = 23), total parathyroidectomy (PTx) with autotransplantation of 45 fragments (n = 25) and PTx with autotransplantation of 90 fragments (n = 21). The questionnaire was completed at three moments: (1) preoperatively, (2) 6 months after surgery, and (3) 12 months after surgery. Results: Quality of life improved significantly in the physical component summary score in all three groups. Subtotal parathyroidectomy scores changed from 30.6 preoperatively to 51.7 6 months after surgery and 53.7 12 months after surgery. Total arathyroidectomy with autotransplantation of 45 fragments scores changed from 33.8 preoperatively to 52.6 6 months after surgery and 55.2 12 months after surgery. Total parathyroidectomy with autotransplantation of 90 fragments scores changed from 31.8 preoperatively to 50.5 6 months after surgery and 55.2 12 months after surgery (all groups P < .0001). No significant difference was detected in the physical component summary score change among the three groups. The physical component summary score was negatively correlated to age, parathormone, and alkaline phosphatase preoperatively. Conclusion: Parathyroidectomy significantly improves quality of life in hemodialysis patients with secondary hyperparathyroidism, regardless of the type of operation.
- Effect of cross-linked chitosan iron (III) on vascular calcification in uremic rats(2018) CASTRO, Barbara Bruna Abreu de; CARMO, Wander Barros do; SUASSUNA, Paulo Giovani de Albuquerque; CARMINATTI, Moises; BRITO, Julia Bianchi; DOMINGUEZ, Wagner Vasques; OLIVEIRA, Ivone Braga de; JORGETTI, Vanda; CUSTODIO, Melani Ribeiro; SANDERS-PINHEIRO, HeladyCross-linked chitosan iron (III) is a chitin-derived polymer with a chelating effect on phosphorus, but it is untested in vascular calcification. We evaluated this compound's ability to reduce hyperphosphatemia and its effect on vascular calcification in uremic rats using an adenine-based, phosphorus-rich diet for seven weeks. We used a control group to characterize the uremia. Uremic rats were divided according the treatment into chronic kidney disease, CKD-Ch-Fe(III)CL (CKD-Ch), CKD-calcium carbonate, or CKD-sevelamer groups. We measured creatinine, phosphorus, calcium, alkaline phosphatase, phosphorus excretion fraction, parathyroid hormone, and fibroblast growth factor 23. Vascular calcification was assessed using the aortic calcium content, and a semi-quantitative analysis was performed using Von Kossa and hematoxylin-eosin staining. At week seven, rats in the chronic kidney disease group had higher creatinine, phosphorus, phosphorus excretion fraction, calcium, alkaline phosphatase, fibroblast growth factor 23, and aortic calcium content than those in the Control group. Treatments with cross-linked chitosan iron (III) and calcium carbonate prevented phosphorus increase (20%-30% reduction). The aortic calcium content was lowered by 88% and 85% in the CKD-Ch and CKD-sevelamer groups, respectively. The prevalence of vascular changes was higher in the chronic kidney disease and CKD-calcium carbonate (62.5%) groups than in the CKD-Ch group (37.5%). In conclusion, cross-linked chitosan iron (III) had a phosphorus chelating effect similar to calcium carbonate already available for clinical use, and prevented calcium accumulation in the aorta.
- CKD-MBD in Brazil: the gap between reality and the recommended guidelines(2018) CUSTÓDIO, Melani Ribeiro
- Bone biopsy in nephrology practice(2018) BARRETO, Fellype de Carvalho; COSTA, Cleber Rafael Vieira da; REIS, Luciene Machado dos; CUSTÓDIO, Melani RibeiroAbstract Renal osteodystrophy (ROD), a group of metabolic bone diseases secondary to chronic kidney disease (CKD), still represents a great challenge to nephrologists. Its management is tailored by the type of bone lesion - of high or low turnover - that cannot be accurately predicted by serum biomarkers of bone remodeling available in daily clinical practice, mainly parathyroid hormone (PTH) and alkaline phosphatase (AP). In view of this limitation, bone biopsy followed by bone quantitative histomorphometry, the gold-standard method for the diagnosis of ROD, is still considered of paramount importance. Bone biopsy has also been recommended for evaluation of osteoporosis in the CKD setting to help physicians choose the best anti-osteoporotic drug. Importantly, bone biopsy is the sole diagnostic method capable of providing dynamic information on bone metabolism. Trabecular and cortical bones may be analyzed separately by evaluating their structural and dynamic parameters, thickness and porosity, respectively. Deposition of metals, such as aluminum and iron, on bone may also be detected. Despite of these unique characteristics, the interest on bone biopsy has declined over the last years and there are currently few centers around the world specialized on bone histomorphometry. In this review, we will discuss the bone biopsy technique, its indications, and the main information it can provide. The interest on bone biopsy should be renewed and nephrologists should be capacitated to perform it as part of their training during medical residency.
- 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.