RESUMO
ABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.
RESUMO Introdução: A radiografia digital (RxD) pode representar uma alternativa adequada para investigar o distúrbio mineral e ósseo (DMO) e a perda de densidade óssea (DO) em modelos de roedores da doença renal crônica (DRC). O objetivo deste estudo foi utilizar a RxD para avaliar a DO em ratos com DRC, e avaliar a correlação entre os achados da RxD e marcadores séricos de DMO e histomorfometria óssea. Métodos: A uremia foi induzida pela alimentação de ratos Wistar com dieta enriquecida com adenina (0,75% por 4 semanas/0,10% por 3 semanas); os resultados foram comparados com um grupo controle nas semanas experimentais 3, 4 e 7. Os seguintes marcadores bioquímicos foram medidos: clearance de creatinina (CCr), fosfato (P), cálcio (Ca), fração excretada de P (FeP), fosfatase alcalina (ALP), fator de crescimento de fibroblastos-23 (FGF-23) e paratormônio (PTH). A imagem da RxD foi obtida e a análise histomorfométrica foi realizada com o fêmur esquerdo. Resultados: como esperado, na semana 7, os ratos urêmicos apresentaram redução do CCr e níveis mais altos de P, FeP e ALP em comparação aos controles. A RxD confirmou a menor DO em animais urêmicos (0,57 ± 0,07 vs. 0,68 ± 0,06 u.a.; p = 0,016) em comparação aos controles no final da semana 7, quando a DMO foi mais proeminente. Uma forma grave de doença óssea de alta renovação celular acompanhou essas mudanças bioquímicas. A DO, medida na RxD foi correlacionada a P (r = -0,81; p = 0,002), ALP (r = -0,69, p = 0,01), PTH (r = -0,83, p = 0,01), OS/BS (r = -0,70 p = 0,02) e Ob.S/BS (r = -0,70; p = 0,02). Conclusão: A DO quantificada por RxD esteve associada às complicações típicas da DMO na DRC e mostrou-se viável na avaliação de alterações ósseas na DRC.
Assuntos
Animais , Masculino , Ratos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Uremia/complicações , Intensificação de Imagem Radiográfica/métodos , Densidade Óssea , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico por imagem , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Uremia/induzido quimicamente , Uremia/sangue , Adenina/efeitos adversos , Biomarcadores/sangue , Remodelação Óssea , Ratos Wistar , Modelos Animais de Doenças , Fosfatase Alcalina/sangue , Insuficiência Renal Crônica/sangueRESUMO
INTRODUCTION: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. METHODS: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. RESULTS: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). CONCLUSION: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.
Assuntos
Densidade Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico por imagem , Uremia/complicações , Adenina/efeitos adversos , Fosfatase Alcalina/sangue , Animais , Biomarcadores/sangue , Remodelação Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Modelos Animais de Doenças , Masculino , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Ratos , Ratos Wistar , Insuficiência Renal Crônica/sangue , Uremia/sangue , Uremia/induzido quimicamenteRESUMO
INTRODUCTION: Chronic kidney disease (CKD) is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD) and bone mineral disorder (CKD-BMD). Uremic toxins, as advanced glycation end products (AGEs), are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF) is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. OBJECTIVE: The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF) and its relations with CVD and BMD parameters in HD patients. METHODS: Twenty prevalent HD patients (HD group) and healthy subjects (Control group, n = 24), performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH), transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. RESULTS: AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. CONCLUSION: Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Pele/metabolismo , Adulto , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Estudos Transversais , Feminino , Produtos Finais de Glicação Avançada/análise , Humanos , Masculino , Imagem Óptica , Projetos Piloto , Pele/diagnóstico por imagemRESUMO
Abstract Introduction: Chronic kidney disease (CKD) is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD) and bone mineral disorder (CKD-BMD). Uremic toxins, as advanced glycation end products (AGEs), are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF) is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. Objective: The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF) and its relations with CVD and BMD parameters in HD patients. Methods: Twenty prevalent HD patients (HD group) and healthy subjects (Control group, n = 24), performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH), transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. Results: AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. Conclusion: Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.
Resumo Introdução: A doença renal crônica (DRC) apresenta elevadas taxas de morbidade e mortalidade, sendo a doença cardiovascular (DCV) e o distúrbio mineral e ósseo da DRC (DMO-DRC) complicações frequentes. As toxinas urêmicas, dentre elas os produtos finais da glicação avançada (AGEs), são fatores de risco cardiovascular não tradicionais e se encontram envolvidas no desenvolvimento do DMO-DRC na DRC. A medida da autofluorescência da pele (sAF) é método não invasivo para quantificação do acúmulo tecidual de AGEs validado em pacientes portadores de DRC. Objetivos: O objetivo deste estudo é avaliar as relações entre os AGEs medidos por sAF (AGEs-AF) e parâmetros de DCV e DMO-DRC em pacientes em hemodiálise (HD). Métodos: 20 pacientes em HD (grupo HD) e 24 indivíduos hígidos (grupo controle) foram submetidos à análise bioquímica sérica, medidas antropométricas e de sAF. O grupo HD realizou medida de hormônio intacto da paratireoide (PTHi), ecocardiograma transtorácico e radiografias de pelve e mãos para pesquisa de calcificação vascular. Resultados: Os níveis de AGEs-sAF foram elevados para a idade nos grupos HD e controle, porém mais elevados no grupo HD. Sessão única de HD de alto-fluxo não afetou os níveis de AGEs-sAF. Os níveis teciduais de AGEs não se correlacionaram com massa ventricular, espessura de septo interventricular ou calcificação vascular no grupo HD. Os níveis de AGEs-sAF se correlacionaram negativamente com os níveis séricos de PTHi. Conclusão: Nosso estudo detectou correlação negativa entre os níveis de AGEs-sAF e os níveis séricos de PTHi, sugerindo que os AGEs estejam envolvidos na fiosiopatologia da doença óssea em pacientes em HD. A natureza desta relação e a aplicação clínica deste método não invasivo de avaliação do acúmulo tecidual de AGEs deve ser confirmada e elucidada por estudos futuros.
Assuntos
Humanos , Masculino , Feminino , Adulto , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Pele/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Pele/diagnóstico por imagem , Projetos Piloto , Estudos Transversais , Produtos Finais de Glicação Avançada/análise , Imagem ÓpticaRESUMO
Abstract. Chronic kidney disease is a public health problem worldwide, with disorders of bone mineralisation and metabolism being common problems associated with this disease, causing significant morbidity and impaired quality of life. The expression of the findings in the chronic kidney disease can be categorised based on the classification proposed by the international conference Kidney Disease: Improving Global Outcomes, that divides them into metabolic disorders of calcium and phosphorus (without findings in radiology), bone structure and composition disorders, and extra-skeletal calcifications. These conditions give characteristic radiographic patterns, such as bone resorption and sclerosis, brown tumours, osteomalacia-rickets, osteopenia, and extra-skeletal calcifications, in addition to treatment related disorders of chronic kidney failure. In this article, concepts related to metabolism disorders and bone mineralisation associated with chronic renal disease and renal osteodystrophy will be categorised and updated, showing their various manifestations in radiology.
La enfermedad renal crónica es un problema de salud pública a nivel mundial, siendo los trastornos de la mineralización y el metabolismo óseo problemas comunes asociados a esta enfermedad, que causan una importante morbilidad y un deterioro de la calidad de vida. La expresión de los hallazgos en la enfermedad renal crónica puede sistematizarse con base en la clasificación propuesta por la conferencia internacional Kidney Disease: Improving Global Outcomes, que las divide en trastornos del metabolismo del calcio y el fósforo (sin hallazgos en imágenes), alteración de la estructura y la composición del hueso, y calcificaciones extraesqueléticas. Estos trastornos otorgan patrones radiológicos característicos, como son la resorción y esclerosis ósea, tumores pardos, osteomalacia-raquitismo, osteopenia y calcificaciones extraesqueléticas, además de los trastornos asociados al tratamiento de la falla renal crónica. En el presente artículo se sistematizarán y actualizarán los conceptos relacionados con los trastornos del metabolismo y la mineralización ósea, asociados a la enfermedad renal crónica y la osteodistrofia renal, mostrando sus diversas manifestaciones en radiología.
Assuntos
Humanos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Esclerose/diagnóstico por imagem , Doenças Ósseas Metabólicas , Reabsorção Óssea/diagnóstico por imagem , Calcinose , Insuficiência Renal Crônica/complicaçõesRESUMO
BACKGROUND: In this study we evaluated bone abnormalities of patients with chronic renal failure (CRF) by cortical quantitative bone ultrasound (QUS) measurements at different bone sites because these abnormalities may be of variable etiology and may start before symptoms or radiological changes are manifested. METHODS: Of fifteen patients with chronic renal failure, seven had moderate-severe disease and eight had been on chronic hemodialysis from 5 to 17 years, with renal osteodystrophy (ROD) confirmed by bone biopsies. Twelve normal subjects of similar age and gender volunteered for the control group. RESULTS: Patients and controls differed in creatinine clearance, in serum phosphate levels and in serum total alkaline phosphatase. Mean intact-PTH levels differed significantly amongst the three groups of subjects. All patients with ROD had intact-PTH higher than 200 pg/mL. The cortical ultrasound parameter, speed of sound (SOS), was slower in patients with more severe renal failure at all bone sites measured. The group with ROD had significantly lower cortical ultrasound values than the other patients and the control group at all sites. SOS values at the proximal phalanx, distal radius and midtibial sites were positively and significantly correlated. Cortical ultrasound measurements at the radial site correlated with midtibial and phalangeal sites but the correlation between midtibial and phalangeal sites did not reach significance. IPTH levels correlated negatively and significantly with cortical QUS values at all sites being the correlations higher at phalangeal and radial sites than at the midtibial region. CONCLUSIONS: The differences in cortical ultrasound observed indicate the potential clinical application of this methodology to evaluate bone abnormalities in chronic renal failure, especially in patients on chronic hemodialysis.
Assuntos
Osso e Ossos/diagnóstico por imagem , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/complicações , Adulto , Fosfatase Alcalina/sangue , Densidade Óssea , Estudos de Casos e Controles , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Creatinina/sangue , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Diálise Renal , Fatores de Tempo , UltrassonografiaAssuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica , Fosfatos/sangue , Absorção , Adolescente , Transporte Biológico Ativo , Calcitriol/metabolismo , Cálcio/sangue , Cálcio/metabolismo , Criança , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/genética , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Absorção Intestinal , Hormônio Paratireóideo/metabolismo , Fosfatos/metabolismo , Fosfatos/uso terapêutico , RadiografiaRESUMO
Fifteen children undergoing continuous ambulatory peritoneal dialysis for 0.3 to 2.4 years were evaluated longitudinally for renal osteodystrophy. Immunoreactive parathyroid hormone, 25-OHD, total and ionized calcium, inorganic phosphate, and alkaline phosphatase levels were measured regularly. Skeletal radiographic studies were performed at the onset and conclusion of CAPD and at six-month intervals during therapy. All children received 1,25(OH)2D3 and aluminum hydroxide, and nine received supplemental calcium. Plasma 25-OHD concentrations were normal to elevated, and calcium increased steadily to high normal levels despite a trend to persistent hyperphosphatemia. The increased calcium levels suppressed parathyroid hormone overactivity in only one patient. At the onset of CAPD, nine patients had hyperparathyroid bone disease seen radiographically, three of whom also had rachitic lesions. At the end of CAPD, the hyperparathyroid lesions had improved in four patients, completely resolved in three, and deteriorated in two. Rachitic lesions had completely healed in two patients and improved in the third. However, among the six children without radiographically evident lesions at onset of CAPD, hyperparathyroid bone lesions developed in two and rachitic lesions in two others during CAPD. Although CAPD and appropriate therapy benefited most patients with renal osteodystrophy, the benefits were not uniform, and bone lesions deteriorated in some.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua , Diálise Peritoneal , Adolescente , Fosfatase Alcalina/sangue , Osso e Ossos/diagnóstico por imagem , Calcifediol/sangue , Cálcio/sangue , Criança , Pré-Escolar , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Feminino , Transtornos do Crescimento/etiologia , Humanos , Lactente , Falência Renal Crônica/complicações , Masculino , Hormônio Paratireóideo/sangue , Fosfatos/sangue , RadiografiaRESUMO
Two siblings, female 10 years old, and male 15 years old, with the diagnosis of vitamin D-dependent rickets were studied. Another sibling, also with the same diagnosis, died of bronchopnemonia at about 7 months of age. Both patients developed rachitic manifestations since the first year of life, which persisted despite the administration of massive doses of vitamin D intermitently. Severe hypocalcemia, moderate hypophosphatemia and elevated serum alkaline phosphatase were the most characteristic biochemical findings. Both patients showed diminished renal tubular reabsorption of amino acids and phosphates. These alterations were reversible during I.V. calcium gluconate administration. The clinical biochemical and X-ray manifestations disappeared completely after one year of treatment with dihydrotaquisterol. Vitamin D-dependent rickets is an autosomal recessive disease, characterized by a hydroxylation defect of 25 hydroxycholecalciferol at the carbon 1 level, due to abscence of 25 hydroxy-D1-hydroxylase. Thus 1-25 Dihydroxycholecalciferol, the active form of vitamin D3 is not formed, resulting in depression of intestinal calcium absorption and reabsorption from the bones.