Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.153
Filtrar
1.
G Ital Nefrol ; 36(4)2019 Jul 24.
Artigo em Italiano | MEDLINE | ID: mdl-31373465

RESUMO

Osteoporosis affects a segment of the population in which Chronic Kidney Disease is also greatly represented. Nephropathic patients may present peculiar biochemical abnormalities related to Chronic Kidney Disease, defining the Mineral and Bone Disorder. This kind of anomalies, in the worst scenarios, configure the typical histomorphology patterns of Renal Osteodystrophy. Scientific Societies of Endocrinology have established therapy guidelines for patients with osteoporosis only based on the glomerular filtration rate and recommend avoiding the use of some drugs for the more advanced classes of nephropathy. However, there is no clear therapeutic approach for patients with advanced nephropathy and bone abnormalities. In this paper we propose a systematic review of the literature and present our proposal for managing patients with advanced nephropathy, based on eGFR and on presence of Mineral and Bone Disorder.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Anticorpos Monoclonais/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/química , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Contraindicações , Denosumab/uso terapêutico , Difosfonatos/efeitos adversos , Difosfonatos/química , Feminino , Fraturas Espontâneas/tratamento farmacológico , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/prevenção & controle , Taxa de Filtração Glomerular , Humanos , Masculino , Osteoporose/complicações , Osteoporose/diagnóstico , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Guias de Prática Clínica como Assunto , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Teriparatida/uso terapêutico
2.
Clin Nephrol ; 91(4): 222-230, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30862350

RESUMO

INTRODUCTION: Renal osteodystrophy (ROD) develops early in chronic kidney disease (CKD) and progresses with loss of kidney function. While intact parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3 (1,25D), and fibroblast growth factor-23 (FGF-23) levels are usually considered the primary abnormalities in ROD development, the role of serum activin A elevations in CKD and its relationships to ROD have not been explored. The aims of this study were to evaluate serum activin A at different CKD stages, and to establish the relationships between activin A, bone biomarkers, and bone histomorphometric parameters. MATERIALS AND METHODS: 104 patients with CKD stages 2 - 5D underwent bone biopsies. We measured in the serum activin A, BSAP, DKK1, FGF-23, α-Klotho, intact PTH, sclerostin, TRAP-5b, and 1,25D. Biochemical results were compared across CKD stages and with 19 age-matched controls with normal kidney function. RESULTS: Median activin A levels were increased in all stages of CKD compared to controls from 544 pg/mL in CKD 2 (431 - 628) to 1,135 pg/mL in CKD 5D (816 - 1,456), compared to 369 pg/mL in controls (316 - 453, p < 0.01). The increase of activin A in CKD 2 (p = 0.016) occurred before changes in the other measured biomarkers. Activin A correlated with intact PTH and FGF-23 (r = 0.65 and 0.61; p < 0.01) and with histomorphometric parameters of bone turnover (BFR/BS, Acf, ObS/BS and OcS/BS; r = 0.47 - 0.52; p < 0.01). These correlations were comparable to those found with intact PTH and FGF-23. CONCLUSION: Serum activin A levels increase starting at CKD 2 before elevations in intact PTH and FGF-23. Activin A correlates with bone turnover similar to intact PTH and FGF-23. These findings suggest a role for activin A in early development of ROD.


Assuntos
Ativinas/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteínas Morfogenéticas Ósseas/sangue , Remodelação Óssea , Estudos de Casos e Controles , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Marcadores Genéticos , Taxa de Filtração Glomerular , Glucuronidase/sangue , Humanos , Subunidades beta de Inibinas , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Fator de Transcrição PAX5/sangue , Hormônio Paratireóideo/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Índice de Gravidade de Doença , Fosfatase Ácida Resistente a Tartarato/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
3.
Am J Physiol Renal Physiol ; 316(1): F90-F100, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30303711

RESUMO

Obesity, metabolic syndrome, and renal injury are considered risk factors for type 2 diabetes, as well as kidney disease. Functional and structural changes in the kidney as consequence of obesity and metabolic syndrome may lead to impaired mineral metabolism in what is known as chronic kidney disease-mineral and bone disorder. Lifestyle interventions such as physical activity are good strategies to manage these pathologies and therefore, prevent the loss of kidney functionality and related complications in mineral metabolism. In this study, we have used 40 male Zucker rats that were randomly allocated into four different experimental groups, two of them (an obese and a lean one) performed an aerobic interval training protocol, and the other two groups were sedentary. At the end of the experimental period (8 wk), urine, plasma, and femur were collected for biochemical and mineral composition analysis, whereas the kidney was processed for histological studies. The obese rats exhibited albuminuria, glomerulosclerosis, and hypertrophy in glomeruli and renal tubule in some areas, together with alterations in mineral content of plasma but not of femur. The training protocol prevented the generation of albuminuria and glomerulosclerosis, showing a significant action on plasma and bone mineral levels. Therefore, the specific training protocol used in this study was able to prevent the development of diabetic nephropathy and affected the metabolism of certain minerals.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Fêmur/metabolismo , Glomerulonefrite/prevenção & controle , Treinamento Intervalado de Alta Intensidade , Rim/fisiopatologia , Minerais/sangue , Obesidade/terapia , Albuminúria/etiologia , Albuminúria/metabolismo , Albuminúria/fisiopatologia , Albuminúria/prevenção & controle , Animais , Biomarcadores/sangue , Biomarcadores/urina , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Modelos Animais de Doenças , Glomerulonefrite/etiologia , Glomerulonefrite/metabolismo , Glomerulonefrite/fisiopatologia , Hipertrofia , Rim/patologia , Masculino , Obesidade/complicações , Obesidade/metabolismo , Obesidade/fisiopatologia , Ratos Zucker , Recuperação de Função Fisiológica , Fatores de Tempo
4.
Int Urol Nephrol ; 51(3): 519-526, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30584645

RESUMO

PURPOSE: Data concerning the relation between increased levels of circulating sclerostin (a physiological inhibitor of bone formation) and bone turnover in patients with chronic renal failure (CRF) are limited. Therefore, the aim of this study was to evaluate associations between plasma sclerostin levels and calcium-phosphate disturbances, markers of bone turnover as well as inflammation in haemodialysis (HD) patients. METHODS: In plasma samples obtained in 150 stable HD patients (92 men) aged 40-70 years, levels of sclerostin, fibroblast growth factor (cFGF23), osteocalcin, the N-terminal propeptide of type I procollagen, C-terminal telopeptide of the alpha chain of type I collagen (ß-CTx), and inflammatory markers (IL-6 and TNF-α) in addition to routine parameters (calcium, phosphorus, parathyroid hormone-iPTH, 25-OH-D, alkaline phosphatase) were measured. RESULTS: Plasma sclerostin concentrations were significantly higher in HD men than women (2.61 vs. 1.88 ng/mL, p < 0.01). Patients with sclerostin levels above median were characterized by lower iPTH and IL-6, but higher cFGF23 and TNF-α (significantly only in men) concentrations. Plasma sclerostin concentration positively correlated with serum 25-OH-D (τ = 0.204), phosphorus (τ = 0.1482), and TNF-α (τ = 0.183) and inversely with iPTH (τ = - 0.255), alkaline phosphatase (τ = - 0.203), IL-6 (τ =- 0.201), and ß-CTx (τ = - 0.099) levels. In multivariate regression analysis, variability of sclerostin levels was explained by sex and 25-OH-D and phosphorus levels. CONCLUSIONS: Increased circulating sclerostin levels seem to reflect slower bone turnover in HD patients. Low levels of sclerostin are associated with vitamin D deficiency and good phosphates alignment.


Assuntos
Proteínas Morfogenéticas Ósseas/sangue , Remodelação Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Adulto , Idoso , Fosfatase Alcalina/sangue , Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Colágeno Tipo I/sangue , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Marcadores Genéticos , Humanos , Inflamação/sangue , Interleucina-6/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Fosfatos/sangue , Fósforo/sangue , Diálise Renal , Fatores Sexuais , Fator de Necrose Tumoral alfa/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
5.
Saudi J Kidney Dis Transpl ; 29(6): 1506-1510, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588988

RESUMO

Periarticular calcification is a frequent radiographic manifestation in chronic kidney disease (CKD). However, clinical presentation as inflammatory periarthritis, tenosynovitis, and bursitis is unusual. A 34-year-old man with CKD on dialysis for three years presented with painful swollen joints. His adherence to regular dialysis, phosphate binders, Vitamin D supplements, and antihypertension therapy was poor. He had swelling of the right thumb, index, and little fingers; periarticular swelling of the left middle finger and right little toe; and extensor tenosynovitis of the wrists and right olecranon bursitis. Laboratory investigations showed the following: urea 36 mmol/L; creatinine 1764 umol/L; serum urate 0.37 mmol/L; corrected calcium 1.76 mmol/L; phosphate 4.32 mmol/L; 25-dihydroxycholecalciferol 30 ng/mL; and parathyroid hormone 104 pmol/L. Radiographs showed periarticular calcification corresponding to the sites of inflammation. The inflammation resolved with oral steroids. In our patient, deranged mineral and bone metabolism contributed to periarticular calcification at multiple sites, mimicking inflammatory polyarthritis.


Assuntos
Artrite/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Articulações dos Dedos/diagnóstico por imagem , Insuficiência Renal Crônica/complicações , Articulação do Dedo do Pé/diagnóstico por imagem , Adulto , Calcinose/etiologia , Calcinose/terapia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Diagnóstico Diferencial , Humanos , Masculino , Valor Preditivo dos Testes , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia
6.
Curr Osteoporos Rep ; 16(6): 693-702, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30291515

RESUMO

PURPOSE OF REVIEW: Although we have seen tremendous advances in the comprehension of CKD-MBD pathophysiology during the last few years, this was not accompanied by a significant change in mortality rate and quality of life. This review will address the traditional and updated pathophysiology of CKD-MBD along with the therapeutic limitations that affect CKD-MBD and proposed alternative treatment targets. RECENT FINDINGS: An innovative concept brings the osteocyte to the center of CKD-MBD pathophysiology, in contrast to the traditional view of the skeleton as a target organ for disturbances in calcium, phosphate, parathyroid hormone, and vitamin D. Osteocytes, through the synthesis of FGF-23, sclerostin, among others, are able to interact with other organs, making bone an endocrine organ. Thus, osteocyte dysregulation might be an early event during the course of CKD. This review will revisit general concepts on the pathophysiology of CKD-MBD and discuss new perspectives for its treatment.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Gerenciamento Clínico , Hiperparatireoidismo Secundário/complicações , Animais , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Suplementos Nutricionais , Humanos
7.
Kidney Int ; 94(5): 1002-1012, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30348285

RESUMO

Pediatric renal osteodystrophy is characterized by skeletal mineralization defects, but the role of osteoblast and osteocyte maturation in the pathogenesis of these defects is unknown. We evaluated markers of osteocyte maturation and programmed cell death in iliac crest biopsy samples from pediatric dialysis patients and healthy controls. We evaluated the relationship between numbers of fibroblast growth factor 23 (FGF23)-expressing osteocytes and histomorphometric parameters of skeletal mineralization. We confirmed that chronic kidney disease (CKD) causes intrinsic changes in bone cell maturation using an in vitro model of primary osteoblasts from patients with CKD and healthy controls. FGF23 co-localized with the early osteocyte marker E11/gp38, suggesting that FGF23 is a marker of early osteocyte maturation. Increased numbers of early osteocytes and decreased osteocyte apoptosis characterized CKD bone. Numbers of FGF23-expressing osteocytes were highest in patients with preserved skeletal mineralization indices, and packets of matrix surrounding FGF23-expressing osteocytes appeared to have entered secondary mineralization. Primary osteoblasts from patients with CKD retained impaired maturation and mineralization characteristics in vitro. Addition of FGF23 did not affect primary osteoblast mineralization. Thus, CKD is associated with intrinsic changes in osteoblast and osteocyte maturation, and FGF23 appears to mark a relatively early stage in osteocyte maturation. Improved control of renal osteodystrophy and FGF23 excess will require further investigation into the pathogenesis of CKD-mediated osteoblast and osteocyte maturation failure.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Osteócitos/fisiologia , Adolescente , Adulto , Apoptose , Criança , Pré-Escolar , Feminino , Fatores de Crescimento de Fibroblastos/análise , Humanos , Masculino , Osteoblastos/fisiologia , Insuficiência Renal Crônica/complicações , Adulto Jovem
8.
Pediatr Nephrol ; 33(9): 1565-1575, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29872964

RESUMO

OBJECTIVE: Mineral and bone disorders associated to chronic kidney disease (CKD-MBD) are a daily challenge for pediatric nephrologists, with a significant risk of long-term bone and vascular comorbidities. METHODS: This single-center study is a prospective transversal evaluation of pediatric CKD patients of our center, part of the European 4C study. In addition to clinical and biochemical data, vascular and bone evaluation was performed: 24-h blood pressure assessment, carotid intima-media thickness (cIMT), pulse wave velocity (PWV), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the ultra-distal tibia. Results are presented as median (range). RESULTS: At a median age of 12.9 years (10.2-17.9), SDS height of - 1.0 (- 3.3-1.2) and estimated glomerular filtration rate (eGFR) of 33 mL/min/1.73m2 (11-72), 32 patients (8 girls) were evaluated. Median calcium, phosphate, parathyroid hormone (PTH), and 25 OHD3 levels were 2.44 mmol/L (2.24-2.78), 1.43 mmol/L (1.0-2.7), 80 pg/mL (9-359), and 70 nmol/L (32-116), respectively. Bivariate Spearman and backward multivariable analyses showed that calcium and bone trabecular thickness (Tb.Th), were positively associated with diastolic and mean arterial blood pressure (both for the 24 h, day and night assessment), whereas PTH and vitamin D did not predict blood pressure. CONCLUSIONS: We show that the greater the serum levels of calcium, the greater the (diastolic and mean) blood pressure; moreover, the greater the Tb. Th, the greater the (diastolic and mean) blood pressure. The role of calcium supplements to explain such findings in early pediatric CKD can be discussed.


Assuntos
Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Calcificação Vascular/fisiopatologia , Adolescente , Pressão Sanguínea/fisiologia , Densidade Óssea/fisiologia , Cálcio/fisiologia , Cálcio na Dieta/administração & dosagem , Cálcio na Dieta/efeitos adversos , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/fisiopatologia , Espessura Intima-Media Carotídea , Criança , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Estudos Prospectivos , Análise de Onda de Pulso , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Tomografia Computadorizada por Raios X , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico , Calcificação Vascular/etiologia
9.
Clin J Am Soc Nephrol ; 13(11): 1738-1746, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-29915131

RESUMO

Ensuring patient safety is a priority of medical care because iatrogenic injury has been a primary concern. Medications are an important source of medical errors, and kidney disease is a thoroughfare of factors threatening safe administration of medicines. Principal among these is reduced kidney function because almost half of all medications used are eliminated via the kidney. Additionally, kidney patients often suffer from multimorbidity, including diabetes, hypertension, and heart failure, with a range of prescribers who often do not coordinate treatments. Patients with kidney disease are also susceptible to further kidney injury and metabolic derangements from medications, which can worsen the disease. In this review, we will present the key issues and threats to safe medication use in kidney disease, with a focus on predialysis CKD, as the scope of medication safety in ESKD and transplantation are unique and deserve their own consideration. We discuss drugs that need to be avoided or dose modified, and review the complications of a range of medications routinely administered in CKD, as these also call for cautious use.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Transplante de Rim , Segurança do Paciente , Insuficiência Renal Crônica/fisiopatologia , Anemia/tratamento farmacológico , Anemia/etiologia , Anemia/terapia , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Diuréticos/efeitos adversos , Humanos , Hiperpotassemia/tratamento farmacológico , Hiperpotassemia/etiologia , Hipopotassemia/tratamento farmacológico , Hipopotassemia/etiologia , Falência Renal Crônica/fisiopatologia , Reconciliação de Medicamentos , Insuficiência Renal Crônica/complicações
10.
Oral Maxillofac Surg ; 22(3): 323-327, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29725779

RESUMO

Hyperparathyroidism (HPT) is an endocrine metabolic disorder characterized by increased secretion of parathyroid hormone. Untreated secondary HPT leads to renal osteodystrophy (ROD). Facial skeletal abnormalities in patients with ROD are rare. The purpose of this paper is to report a conservative surgical approach of exuberant osteitis fibrosa lesions in patient with chronic kidney disease. A 24-year-old female was referred to maxillofacial surgery department with giants ROD affecting palate, maxilla, and mandible, resulting in esthetic and functional impairment. The pathogeneses and multidisciplinary management of ROD are discussed with a brief literature review. Eight years after the conservative treatment of exuberant jaw lesions, no noticeable bone changes were observed in the patient. A multidisciplinary therapy is essential for correct diagnosis of ROD and optimal multimodality treatment. The conservative management was an efficient alternative for the success of the case reported.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Hiperparatireoidismo Secundário/complicações , Falência Renal Crônica/complicações , Doenças Mandibulares/etiologia , Doenças Mandibulares/cirurgia , Doenças Maxilares/etiologia , Doenças Maxilares/cirurgia , Procedimentos Cirúrgicos Bucais/métodos , Osteíte Fibrosa Cística/etiologia , Osteíte Fibrosa Cística/cirurgia , Palato/patologia , Palato/cirurgia , Diagnóstico Diferencial , Estética Dentária , Feminino , Humanos , Imagem Tridimensional , Falência Renal Crônica/cirurgia , Transplante de Rim , Doenças Mandibulares/diagnóstico por imagem , Doenças Maxilares/diagnóstico por imagem , Palato/diagnóstico por imagem , Retalhos Cirúrgicos , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
Kidney Int ; 94(1): 102-113, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29716795

RESUMO

Chronic kidney disease (CKD) causes dysregulation of mineral metabolism, vascular calcification and renal osteodystrophy, an entity called 'CKD-Mineral and Bone Disorder' (CKD-MBD). Here we determine whether metformin, an anti-diabetic drug, exerts favorable effects on progressive, severe CKD and concomitant mineral metabolism disturbances. Rats with CKD-MBD, induced by a 0.25% adenine diet for eight weeks, were treated with 200 mg/kg/day metformin or vehicle from one week after CKD induction onward. Severe, stable CKD along with marked hyperphosphatemia and hypocalcemia developed in these rats which led to arterial calcification and high bone turnover disease. Metformin protected from development toward severe CKD. Metformin-treated rats did not develop hyperphosphatemia or hypocalcemia and this prevented the development of vascular calcification and inhibited the progression toward high bone turnover disease. Kidneys of the metformin group showed significantly less cellular infiltration, fibrosis and inflammation. To study a possible direct effect of metformin on the development of vascular calcification, independent of its effect on renal function, metformin (200 mg/kg/day) or vehicle was dosed for ten weeks to rats with warfarin-induced vascular calcification. The drug did not reduce aorta or small vessel calcification in this animal model. Thus, metformin protected against the development of severe CKD and preserved calcium phosphorus homeostasis. As a result of its beneficial impact on renal function, associated comorbidities such as vascular calcification and high bone turnover disease were also prevented.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Calcificação Vascular/prevenção & controle , Adenina/toxicidade , Animais , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Wistar , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/metabolismo , Índice de Gravidade de Doença , Resultado do Tratamento , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Varfarina/toxicidade
12.
Nephrol Dial Transplant ; 33(12): 2092-2100, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29733407

RESUMO

Recent improvements in our understanding of physiology have altered the way in which bone is perceived: no longer is it considered as simply the repository of divalent ions, but rather as a sophisticated endocrine organ with potential extraskeletal effects. Indeed, a number of pathologic conditions involving bone in different ways can now be reconsidered from a bone-centred perspective. For example, in metabolic bone diseases like osteoporosis (OP) and renal osteodystrophy (ROD), the association with a worse cardiovascular outcome can be tentatively explained by the possible derangements of three recently discovered bone hormones (osteocalcin, fibroblast growth factor 23 and sclerostin) and a bone-specific enzyme (alkaline phosphatase). Further, in recent years the close link between bone and inflammation has been better appreciated and a wide range of chronic inflammatory states (from rheumatoid arthritis to ageing) are being explored to discover the biochemical changes that ultimately lead to bone loss and OP. Also, it has been acknowledged that the concept of the bone-vascular axis may explain, for example, the relationship between bone metabolism and vessel wall diseases like atherosclerosis and arteriosclerosis, with potential involvement of a number of cytokines and metabolic pathways. A very important discovery in bone physiology is the bone marrow (BM) niche, the functional unit where stem cells interact, exchanging signals that impact on their fate as bone-forming cells or immune-competent haematopoietic elements. This new element of bone physiology has been recognized to be dysfunctional in diabetes (so-called diabetic mobilopathy), with possible clinical implications. In our opinion, ROD, the metabolic bone disease of renal patients, will in the future probably be identified as a cause of BM niche dysfunction. An integrated view of bone, which includes the BM niche, now seems necessary in order to understand the complex clinical entity of chronic kidney disease-mineral and bone disorders and its cardiovascular burden. Bone is thus becoming a recurrently considered paradigm for different inter-organ communications that needs to be considered in patients with complex diseases.


Assuntos
Doenças Ósseas Metabólicas/complicações , Medula Óssea/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Inflamação/complicações , Osteoporose/complicações , Insuficiência Renal Crônica/fisiopatologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Humanos
13.
Int Urol Nephrol ; 50(6): 1181-1188, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29644525

RESUMO

PURPOSE: Chronic kidney disease (CKD) is a progressive condition characterized by irreversible loss of functional nephron mass due to variety of causes; an inevitable complication of CKD is metabolic bone disease, and this pathology is called as renal osteodystrophy (ROD). In this study, we aimed to determine the levels of serum sRANKL and intracellular NF-κB levels in peripheral blood osteoclast precursor cells in patients with stage 3 CKD. MATERIALS AND METHODS: Forty-one male patients aged 35-60 with CKD identified as stage 3 according to GFR calculated on the basis of creatinine values and 27 healthy male subjects with age ranging from 40 to 60 as control group were included in this study. Levels of biochemical parameters, vitamin D3, parathyroid hormone, bone mineral density, sRANKL and NF-κB were determined by using photometric, electrochemiluminescence, HPLC, ELISA and flow cytometric methods in control and patient groups, respectively. RESULTS: When stage 3 CKD patients were compared with controls, patients with stage 3 CKD had statistically significantly higher iPTH levels, but they had statistically significantly lower vitamin D3 levels. However, the other biochemical parameters, bone mineral density, sRANKL and NF-κB levels did not reveal any significance. CONCLUSION: In conclusion, vitamin D3 and iPTH levels seem to be important parameters for evaluating the early stages of ROD. The lack of statistically significant differences in the levels of sRANKL and NF-κB suggests that these parameters are not sufficient in the evaluation of bone metabolism in the early stages of renal failure.


Assuntos
Colecalciferol/sangue , NF-kappa B/sangue , Hormônio Paratireóideo/sangue , Ligante RANK/sangue , Insuficiência Renal Crônica/sangue , Células-Tronco/metabolismo , Adulto , Densidade Óssea , Estudos de Casos e Controles , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoclastos , Insuficiência Renal Crônica/complicações
14.
G Ital Nefrol ; 35(2)2018 Mar.
Artigo em Italiano | MEDLINE | ID: mdl-29582958

RESUMO

CKD-MBD is a systemic disorder of the mineral and bone metabolism as a result of CKD. The clinical relevance of this syndrome has led to the identification of the biochemical targets to be achieved in order to improve the outcome of the patient. However, in hemodialysis (HD) and peritoneal dialysis (DP) patients, these targets are not reached. Hyperphosphatemia is a predictor of cardiovascular and all-cause mortality. In DP the removal of phosphorus (P) occurs by diffusion and convection, with a contribution of ultrafiltration of about 11%. P clearance is time dependent, with differences between CAPD and APD and depending on membrane transport characteristics. Residual renal function plays a key role in the P balance. Calcium (Ca) clearance in PD depends on the calcium levels, calcium concentration in dialysate and ultrafiltration. Positive Ca balance brings to Adynamic Bone Disease. Several bone-derived substances, some of them with hormonal action, have shed new light on the bone- cardiac axis. The hormonal functions of bone are likely to be related to histological lesions that develop during chronic renal failure. Compared to the past, recent data show less obvious differences in bone histomorphometry parameters between HD patients and PD patients. However, in PD patients fewer fractures are reported, probably due to different bone quality.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Diálise Peritoneal/efeitos adversos , Osso e Ossos/metabolismo , Cálcio/metabolismo , Sistema Cardiovascular/fisiopatologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/prevenção & controle , Hormônios/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Membranas Artificiais , Fósforo/metabolismo , Ultrafiltração , Vitamina D/metabolismo
15.
J Am Soc Nephrol ; 29(5): 1557-1565, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29555831

RESUMO

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry.Methods We obtained fasting blood samples from 69 patients with CKD stages 4-5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD.Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.


Assuntos
Remodelação Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Fosfatase Alcalina/sangue , Área Sob a Curva , Biomarcadores/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Curva ROC , Rádio (Anatomia)/diagnóstico por imagem , Fosfatase Ácida Resistente a Tartarato/sangue , Tíbia/diagnóstico por imagem
16.
Nefrologia ; 38(1): 27-33, 2018.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29137893

RESUMO

Bone disease related to chronic kidney disease and, particularly, to kidney transplant patients is a common cause or morbidity and mortality, especially due to a higher risk of osteoporotic fractures. Despite the fact that this has been known for decades, to date, an appropriate diagnostic strategy has yet to be established. Apart from bone biopsy, which is invasive and scarcely used, no other technique is available to accurately establish the risk of fracture in kidney patients. Techniques applied to the general population, such as bone densitometry, have not been subjected to sufficient external validation and their use is not systematic. This means that the identification of patients at risk of fracture and therefore those who are candidates for preventive strategies is an unmet need. Bone strength, defined as the ability of the bone to resist fracture, is determined by bone mineral density (measured by bone densitometry), trabecular architecture and bone tissue quality. The trabecular bone score estimates bone microarchitecture, and low values have been described as an independent predictor of increased fracture risk. Bone microindentation is a minimally invasive technique that measures resistance of the bone to micro-cracks (microscopic separation of mineralised collagen fibres), and therefore bone tissue biomechanical properties. The superiority over bone densitometry of the correlation between the parameters measured by trabecular bone score and microindentation with the risk of fracture in diverse populations led us to test its feasibility in chronic kidney disease and kidney transplant patients.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Transplante de Rim , Absorciometria de Fóton , Densidade Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Estudos de Coortes , Fraturas Espontâneas/epidemiologia , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/prevenção & controle , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/etiologia , Fraturas de Estresse/prevenção & controle , Necessidades e Demandas de Serviços de Saúde , Humanos , Complicações Pós-Operatórias/diagnóstico , Risco , Transplantados
17.
J Atheroscler Thromb ; 25(2): 170-177, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28674323

RESUMO

AIM: Chronic kidney disease-mineral bone disorder (CKD-MBD) is associated with all-cause and cardiovascular morbidity and mortality in patients with CKD. Thus, elucidating its pathophysiological mechanisms is essential for improving the prognosis. We evaluated characteristics of CKD-MBD in a newly developed CKD rat model. METHODS: We used male Sprague-Dawley (SD) rats and spontaneously diabetic Torii (SDT) rats, which are used as models for nonobese type 2 diabetes. CKD was induced by 5/6 nephrectomy (Nx). At 10 weeks, the rats were classified into six groups and administered with a vehicle or a low- or high-dose paricalcitol thrice a week. At 20 weeks, the rats were sacrificed; blood and urinary biochemical analyses and histological analysis of the aorta were performed. RESULTS: At 20 weeks, hemoglobin A1c (HbA1c) levels, blood pressure, and renal function were not significantly different among the six groups. Serum calcium and phosphate levels tended to be higher in SDT-Nx rats than in SD-Nx rats. The urinary excretion of calcium and phosphate was significantly greater in SDT-Nx rats than in SD-Nx rats. After administering paricalcitol, serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels were significantly higher in SDT-Nx rats than in SD-Nx rats. The degree of aortic calcification was significantly more severe and the aortic calcium content was significantly greater in SDT-Nx rats than in SD-Nx rats. CONCLUSIONS: We suggest that our new CKD rat model using SDT rats represents a useful CKD-MBD model, and this model was greatly influenced by paricalcitol administration. Further studies are needed to clarify the detailed mechanisms underlying this model.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Diabetes Mellitus Tipo 2/complicações , Modelos Animais de Doenças , Calcificação Vascular , Animais , Pressão Sanguínea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
18.
Nefrologia ; 38(2): 179-189, 2018.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28676189

RESUMO

BACKGROUND: In routine clinical practice, the prescription of vitamin D analogues (VDA) in patients with chronic kidney disease (CKD) is often associated with a decline of the estimated renal function. The reason for this is not fully understood. AIMS: To analyse the effects of VDA discontinuation in advanced CKD and to determine the factors associated with changes in renal function. MATERIAL AND METHODS: Retrospective cohort study of adult patients with advanced CKD. The case subgroup was treated with VDA and this medication was discontinued at baseline (the first visit). The control subgroup was not treated with VDA and they were selected according to comparability principles for CKD progression by propensity score matching. The primary outcome measure was a change to both the estimated glomerular filtration rate (MDRD-GFR) and the measured glomerular filtration rate (mGFR by combined creatinine and urea clearances). Baseline parameters related to mineral metabolism and creatinine generation were analysed as potential determinants of renal function changes. RESULTS: The study sample consisted of 67 cases and 67 controls. Renal function improved in 67% of cases and worsened in 72% of controls (p<0.0001). Changes in MDRD-GFR for the case subgroup and the control subgroup were +0.455±0.997 vs. -0.436±1.103ml/min/1.73 m2/month (p<0.0001), respectively. Total creatinine excretion was slightly higher in cases than in controls but the difference was not significant. According to multivariate logistic and linear regression analyses, baseline total serum calcium was one of the best determinants of both renal function recovery (Odds ratio=3.49; p=0.001), and of the extent of renal function recovery (beta=0.276; p=0.001). CONCLUSIONS: Discontinuation of VDA treatment in CKD patients is associated with significant recovery of estimated renal function. The extent of these changes is mainly associated with baseline total serum calcium.


Assuntos
Insuficiência Renal Crônica/fisiopatologia , Vitamina D/efeitos adversos , Idoso , Cálcio/sangue , Estudos de Casos e Controles , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Proteinúria/etiologia , Recuperação de Função Fisiológica , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico
19.
Afr Health Sci ; 18(2): 446-457, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30602972

RESUMO

Backround: Secondary hyperparathyroidism (SHPT) is a manifestation of chronic kidney disease mineral bone disorder (CKD-MBD). SHPT is common in patients with chronic kidney disease (CKD) and is associated with significant morbidity and mortality. Methods: A cross- sectional descriptive study involving 230 patients with CKD. Results: The mean age of the study population was 44.17±15.24 years. The median intact parathyroid hormone and alkaline phosphatase levels were 96pg/ml (range 4-953pg/ml) and 88 iu/l (range 10-800 iu/l) respectively. The mean (with standard deviation) calcium, serum phosphate, calcium phosphate product and haemoglobin levels were 2.22±0.29mmol/l, 1.8±0.62mmol/l, 3.94±1.42mmol2/l2 and 9.90±1.87g/dl respectively. Majority of patients had advanced CKD with 70.3% of patients in stage G5. The prevalence rates of SHPT, hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase and elevated calcium phosphate product were 55.2%, 34.8%, 66.1%, 42.2% and 25.2% respectively.Univariate analysis revealed that SHPT was associated with hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase, proteinuria, anaemia, hypertension, left ventricular hypertrophy and stage of kidney disease; being worse with advancing kidney disease. Independently associated with SHPT were hypocalcaemia (OR=4.84), hyperphosphataemia (OR=3.06), and elevated alkaline phosphatase (OR=2.04). Conclusion: The prevalence of SHPT in CKD is high, occurs early and is independently associated with hypocalcaemia, hyperphosphataemia and elevated alkaline phosphatase. The prevalence of SHPT also increases with worsening renal function.


Assuntos
Fosfatase Alcalina/sangue , Hiperparatireoidismo Secundário/etiologia , Hormônio Paratireóideo/sangue , Diálise Renal/efeitos adversos , Adulto , Idoso , Cálcio/sangue , Fosfatos de Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/epidemiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Estudos Transversais , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/epidemiologia , Hiperfosfatemia/epidemiologia , Hipocalcemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia
20.
G Ital Nefrol ; 34(Nov-Dec)2017 Dec 05.
Artigo em Italiano | MEDLINE | ID: mdl-29207223

RESUMO

Fragility fractures (FF) are common in patients with chronic kidney disease (CKD), and they occur at a younger age and with a higher frequency than in the general population, producing significant morbidity, mortality and healthcare costs. The pathogenic mechanisms underlying FF in CKD patients have not been completely understood. Behind CKD-MBD, the uremic toxicity should play a role in their pathogenesis, by affecting bone quality (uremic osteoporosis). There are very few prospective studies investigating risk factors for fragility fractures in CKD patients, and available algorithms for fracture risk prediction (FRAX and DeFRA) have never considered CKD. The diagnosis of vertebral fractures (FV), under-diagnosed in CKD patients as well as in general population, should be performed by Quantitative Vertebral Morphometry (QVM) both with DXA or Spine (D4-L5) x-Ray. A recent KDIGO review has qualified the measurement of the Bone Mineral Density by DXA as a predictive tool for fracture risk assessment in patients with stage G3a-G5D. Furthermore, the Trabecular Bone Score (TBS, software applied to DXA) allows the bone quality evaluation as well as the fracture risk prediction. Other techniques, such as Quantitative Computerized Tomography (QCT), especially High Resolution-peripheral QCT (HR-pQCT), have been shown to be useful, although expensive. Finally, some bone biomarkers (PTH and BAP) demonstrated to be informative for the definition of fracture risk in patients with CKD-MBD. In conclusion, there are several different tools and approaches that demonstrated to be useful for the identification of CKD patients at high risk of fracture, when these are appropriately performed and interpreted by expertise clinicians.


Assuntos
Fraturas Espontâneas/etiologia , Insuficiência Renal Crônica/complicações , Densidade Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Feminino , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/epidemiologia , Fraturas Espontâneas/prevenção & controle , Humanos , Incidência , Masculino , Modelos Biológicos , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Prevalência , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/terapia , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia , Tomografia Computadorizada por Raios X/métodos , Uremia/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA