MELANI RIBEIRO CUSTODIO

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

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Assunto: chronic kidney-disease ×

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  • article 1 Citação(ões) na Scopus
    Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats
    (2022) CARMO, Wander Barros do; CASTRO, Barbara Bruna Abreu; MANSO, Luisa Cardoso; CARMO, Priscylla Aparecida Vieira do; RODRIGUES, Clovis Antonio; CUSTODIO, Melani Ribeiro; JORGETTI, Vanda; SANDERS-PINHEIRO, Helady
    Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO3) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO3 groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 +/- 18.6 vs. 41.5 +/- 22.1 mu mol/L; P = 0.001), phosphate (3.5 +/- 0.8 vs. 2.2 +/- 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 +/- 0.2 vs. 0.2 +/- 0.17; P = 0.0001), and FGF23 (81.36 +/- 37.16 pg/mL vs. 7.42 +/- 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 +/- 0.20; CKD/CH-FeCl: 0.40 +/- 0.16; CKD/CaCO3 0.34 +/- 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.
  • article 2 Citação(ões) na Scopus
    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, Helady
    Phosphate 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.
  • article 30 Citação(ões) na Scopus
    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.
  • article 32 Citação(ões) na Scopus
    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.