Melani Ribeiro Custódio

Osteoporosis After Transplantation

Transplantation is an established therapy for end-stage diseases of kidney, lung, liver, and heart among others. Osteoporosis and fragility fractures are serious complications of organ transplantation, particularly in the first post-transplant year. Many factors contribute to the pathogenesis of osteoporosis following organ transplantation. This review addresses the mechanisms of bone loss that occurs both in the early and late post-transplant periods, including the contribution of the immunosuppressive agents as well as the specific features to bone loss after kidney, lung, liver, cardiac, and bone marrow transplantation. Prevention and treatment for osteoporosis in the transplant recipient are also discussed.

Parathyroidectomy Improves Survival In Patients with Severe Hyperparathyroidism: A Comparative Study

Background and objectives Secondary hyperparathyroidism (SHPT) in CKD is associated with an increased risk for mortality, but definitive data showing that parathormone control decreases mortality is still lacking. This study aimed to compare the mortality of patients with severe SHPT submitted to parathyroidectomy(PTX) with those who did not have access to surgery. Methods This is a retrospective study in a cohort of 251 CKD patients with severe SHPT who were referred to a CKD-MBD Center for PTX from 2005 until 2012. Results Most of our patients had indication of PTX, but only 49% of them had access to this surgical procedure. After a mean follow-up of 23 months, 72 patients had died. Non-survivors were older; more often had diabetes, lower serum 25 vitamin D and mostly had not been submitted to surgery. The relative risk of death was lower in the PTX patients (0.428; 95% CI, 0.28 to 0.67; p<0.0001). After adjustments, mortality risk was dependent on age (1.04; 95% CI, 1.01 to 1.07; p = 0.002), 25 vitamin D (0.43; 95% CI, 0.24 to 0.81; p = 0.006) and no access to PTX (4.13; 95% CI, 2.16 to 7.88; p<0.0001). Results remained the same in a second model using the PTX date as the study start date for the PTX group. Conclusions Our data confirms the benefit of PTX on mortality in patients with severe SHPT. The high mortality encountered in our population is significant and urges the need to better treat these patients.

Successful implant of long-term cryopreserved parathyroid glands after total parathyroidectomy

Parathyroid cryopreservation is essential in some cases of parathyroid surgery. The fate of autografted tissue after long‐term cryopreservation is not fully discussed in the literature.

Bone disease after transplantation: osteoporosis and fractures risk

Organ transplantation is the gold standard therapy for several end-stage diseases. Bone loss is a common complication that occurs in transplant recipients. Osteoporosis and fragility fractures are serious complication, mainly in the first year post transplantation. Many factors contribute to the pathogenesis of bone disease following organ transplantation. This review address the mechanisms of bone loss including the contribution of the immunosuppressive agents as well as the specific features to bone loss after kidney, lung, liver, cardiac and bone marrow transplantation. Prevention and management of bone loss in the transplant recipient should be included in their post transplant follow-up in order to prevent fractures.

Biopsy vs. peripheral computed tomography to assess bone disease in CKD patients on dialysis: differences and similarities

SummaryResults 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.IntroductionChronic 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.MethodsHR-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.ResultsWe 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.ConclusionsThere 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 Bone Histology Spectrum in Experimental Renal Failure: Adverse Effects of Phosphate and Parathyroid Hormone Disturbances

Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.

Protocolo clínico e diretrizes terapêuticas para o tratamento do hiperparatireoidismo secundário em pacientes com doença renal crônica

INTRODUCAO A doenca renal cronica (DRC) afeta 5-10% da populacao mundial e sua incidencia no Brasil tem aumentado, devido ao numero crescente de pacientes diagnosticados, principalmente os portadores de diabetes mellitus, hipertensao arterial, bem como pelo aumento da longevidade da populacao. […] Protocolo clinico e diretrizes terapeuticas para o tratamento do hiperparatireoidismo secundario em pacientes com doenca renal cronica1 Serviço de Nefrologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil. 2 Serviço de Nefrologia da Universidade Federal de São Paulo, São Paulo, Brasil. 3 Escola de Medicina, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brasil. 4 Departamento de Medicina Interna da Universidade Federal da Bahia, Brasil. 5 Serviço de Nefrologia da Universidade Federal do Rio Grande do Sul, Brasil. 6 Serviço de Nefrologia da Universidade Federal Fluminense, Niterói, RJ, Brasil. 7 Serviço de Nefrologia da Universidade Federal de Pernambuco, Brasil.

Guidelines on Bone Mineral Disorder in Chronic Kidney Disease - Addendum Chapter 2

1 – AVALIACAO DOS NIVEIS DE PARATORMONIO (PTH) E FOSFATASE ALCALINA (FA) NA DRC 1.1 – Os niveis sericos de PTH devem ser analisados em todos os pacientes com DRC, cuja taxa de filtracao glomerular (TFG) for inferior a 60 mL/min/1,73 m2 (Evidencia). Deve-se modificar a frequencia de avaliacao dos niveis sericos de PTH se os resultados das analises mostrarem uma tendencia de elevacao ou de descenso ou apos a instituicao do tratamento, seja ele para reduzir ou elevar os [...]

Bone Disease in Newly Diagnosed Lupus Nephritis Patients

Introduction Bone loss in Lupus Nephritis (LN) patients is common and multifactorial. The aim of this study was to evaluate the bone status of newly diagnosed LN patients and their correlation with inflammatory factors involved in LN physiopathology. Methods We studied 15 pre-menopausal patients with ≤2 months of diagnosed SLE and LN. Patients with prior kidney or bone disease were excluded. In addition to biochemical evaluation (including 25-hydroxyvitamin D3 [25(OH)D] and Monocyte Chemotactic Protein (MCP1) dosage), we performed bone biopsies followed by osteoblast culture, histomorphometric and immunohistochemistry analysis. Results LN patients presented a mean age of 29.5±10 years, a proteinuria of 4.7±2.9 g/day and an estimated glomerular filtration rate (GFR) of 37(31–87) ml/min/1,73 m2. They were on glucocorticoid therapy for 34±12 days. All patients presented vitamin D insufficiency (9.9±4.4 ng/ml, range 4–20). Urinary MCP1 correlated negatively with 25(OH)D (r = −0.53, p = 0.003) and positively with serum deoxypyridinoline (r = 0.53, p = 0.004). Osteoblasts isolated from LN bone biopsies presented a significantly higher expression of MCP-1 when compared to controls (32.0.±9.1 vs. 22.9±5.3 mean fluorescence intensities, p = 0.01). LN patients presented a significantly reduced osteoid volume, osteoid thickness, osteoid surface, mineralization surface and bone formation rate, associated with an increased eroded surface and osteoclast surface. Patient’s bone specimens demonstrated a reduced immunostaining for osteoprotegerin (0.61±0.82 vs. 1.08±0.50%, p = 0.003), and an increased expression of Receptor Activator of NF-κB ligand (RANKL) (1.76±0.92 vs. 0.41±0.28%, p<0.001) when compared to controls. Discussion Newly diagnosed LN patients presented a significant disturbance in bone metabolism, characterized by an impaired bone formation and mineralization, associated with an increase in resorption parameters. Glucocorticoid use, vitamin D insufficiency and inflammation might be involved in the physiopathology of bone metabolism disturbance.

Distúrbio mineral e ósseo após o transplante renal

O transplante renal (TxR) e a melhor alternativa de tratamento para os pacientes com DRC avancada. Entretanto, apesar do sucesso dessa terapia, os pa-cientes submetidos ao TxR podem apresentar elevada incidencia de complicacoes, dentre elas a persistencia da doenca ossea, piorando a qualidade de vida e au-mentando a morbimortalidade. O TxR bem sucedido geralmente corrige ou melhora os disturbios do meta -bolismo mineral e osseo (DMO) da DRC, e a persis-tencia dessas alteracoes sao determinadas pela magni -tude das anormalidades no periodo dialitico, disfun-cao do enxerto e acao de drogas imunossupressoras. Muitas das alteracoes do metabolismo mineral que ocorrem logo apos o TxR tendem a se normali-zar no decorrer do primeiro ano. A hipofosfatemia, acompanhada de fosfaturia, ocorre em 90% dos pa-cientes transplantados, e geralmente apresenta reso-lucao do quadro ate o terceiro mes, permanecendo no limite inferior da normalidade.