Metabolismo óseo-mineral en 4620 pacientes prevalentes en hemodiálisis crónica en argentina / Bone-mineral metabolism in 4,620 prevalent patients in chronic hemodialysis in argentina

RESUMEN Introducción: Las anormalidades del metabolismo óseo-mineral comienzan desde las primeras etapas de la enfermedad renal crónica, produciendo el desarrollo de enfermedad ósea y el aumento de la morbimortalidad de los pacientes. Objetivos: Conocer en una muestra representativa de nuestra población en hemodiálisis, la prevalencia de pacientes en rango objetivo de valores de parathormona, hiperparatiroidismo secundario y enfermedad ósea adinámica, de acuerdo con las guías KDIGO, evaluando, además, el uso de diferentes medicamentos en el control de estas alteraciones. Material y métodos: Participaron 39 centros de hemodiálisis de nuestro país, quienes enviaron las últimas determinaciones de calcio, fósforo y parathormona, y la medicación recibida en el manejo del metabolismo mineral. Resultados: Se incluyeron 4620 pacientes prevalentes en hemodiálisis, > 18 años, edad media 57 años, hombres 57,4%. Las medias fueron: calcemia 8,6 y fosfatemia 4,9 mg/dl. De esta población, el 56,7% y el 50,3% estaban en rango de calcemia y fosfatemia, respectivamente. La parathormona promedio fue 601 y la mediana 437 pg/ml. El 50,5% tenía parathormona en rango, el 15% por debajo de 150 y el 34,5% por encima de 600 pg/ml. En relación a la medicación, el 47% de la población recibió quelantes cálcicos, con extremos en su uso, que van desde el 4,5% al 8% en algunos centros, y del 83% al 94% en otros. El 28,8% recibió Sevelamer, calcitriol el 38%, paricalcitol el 11% y cinacalcet el 20%, siendo su uso variable según los centros del 3% al 52%. Conclusiones: La presencia de hiperparatiroidismo secundario es más frecuente que la deseada, probablemente vinculado a la dificultad en el uso adecuado de medicamentos.

ABSTRACT Introduction : Abnormalities of bone mineral metabolism begin from the early stages of CKD, causing the development of bone disease and increased morbidity and mortality of patients. Objectives: To know, in a representative sample of our hemodialysis patients, the prevalence of patients in the target range of PTH values, secondary hyperparathyroidism and adynamic bone disease according to the KDIGO guidelines, also evaluating the use of different drugs in the control of these alterations. Methods: 39 hemodialysis centers from our country participated, who sent the latest determinations of calcium, phosphorus and PTH and the medication received in the management of mineral metabolism. Results: 4620 prevalent hemodialysis patients > 18 years were included, mean age 57 years, men 57.4%. The means were calcemia 8.6 and phosphatemia 4.9 mg/dl. 56.7% and 50.3% were in the calcemia and phosphatemia range, respectively. The average PTH was 601 and the median 437 pg/ml. 50.5% had PTH in range, 15% below 150 pg/ml and 34.5% above 600 pg/ml. In relation to medication, 47% of the patients received calcium chelators with extreme use ranging from 4.5-8% in some centers to 83-94%. 28.8% received Sevelamer, calcitriol 38%, paricalcitol 11% and cinacalcet 20%, its use being variable according to the centers from 3% to 52%. Conclusion: the presence of secondary hyperpartyroidism was more frequent than desired, probably linked to the difficulty in the adequate use of medications.

Calcifilaxis en terapia de sustitución renal / Calcifilaxis in renal substitution therapy

Resumen La calcifilaxis es una de las complicaciones menos comunes de la enfermedad renal crónica avanzada, sobretodo en terapia de sustitución renal, se desconoce la fisiopatología exacta de aparición, pero se cree, que es por una alteración en el metabolismo óseo-mineral. Se describe un caso clínico, de un paciente con enfermedad renal crónica, que presentó como complicación grave calcifilaxis, llegando a dicho diagnóstico gracias a las imágenes características de dicha patología tomadas del banco del servicio de imagenología del hospital. En conclusión, la calcifilaxis, a pesar de ser una patología difícil de encontrar en la actualidad, debido al mejor control del metabolismo óseo-mineral, se debe considerar en aquellos pacientes con progresión rápida de la enfermedad renal y con presencia de lesiones calcificadas supurativas en extremidades.

Abstract Calciphylaxis is one of the less common complications of Chronic Advanced Kidney Disease, especially in renal replacement therapy, the exact pathophysiology of its appearance is unknown, but it is believed that it is due to an alteration in bone-mineral metabolism. We describe a clinical case of a patient with chronic kidney disease, who presented as a serious complication calciphylaxis, reaching this diagnosis thanks to the characteristic images of this pathology taken from the bank of the Hospital's imaging service. In conclusion, calciphylaxis, despite being a pathology difficult to find nowadays due to better control of bone-mineral metabolism, should be considered especially in those patients with rapid progression of renal disease and presence of suppurative calcified lesions in extremities.

Evaluación del metabolismo óseo pre y postrasplante renal en niños y adolescentes / Pre and post-renal transplant bone mineral metabolism in children and adolescents

Introducción. La enfermedad renal crónica presenta efectos sobre el tejido óseo que se conocen como enfermedad renal crónica-trastorno mineral óseo. Los pacientes con trasplante renal también presentan trastornos óseos, aun con la función normal del injerto. Se han atribuido a los medicamentos inmunosupresores (esteroides e inhibidores de calcineurina). Por lo anterior, es necesario conocer la prevalencia y evolución de trastorno mineral óseo pre y postrasplante renal en los niños. El objetivo de este trabajo fue describir la prevalencia y el tipo de alteraciones de metabolismo mineral pretrasplante y su evolución postrasplante. Métodos. El estudio fue aprobado por el Comité de Ética e Investigación del hospital. Se obtuvo el consentimiento informado de todos los participantes. Participaron pacientes con enfermedad renal crónica menores de 18 años, estudiados para recibir un primer trasplante renal. Al momento del trasplante, así como a los 6 y a los 12 meses postrasplante, se realizó la antropometría completa y se colectó sangre para determinar creatinina, niveles en valle de tacrolimus, calcio, fósforo, magnesio y fosfatasa alcalina. Se midió la hormona paratiroidea intacta (PTH) al momento del trasplante. Resultados. Se incluyeron 31 pacientes con edad promedio de 14.6 ± 3.2 años y predominio del sexo femenino (52%). Todos recibieron inducción con basiliximab y triple esquema con prednisona, micofenolato de mofetilo y tacrolimus. En cuanto a los valores de PTH, 51.6% tuvieron cifras pretrasplante <150 pg/ml (sugestivo de lesiones óseas de bajo remodelamiento); 38.7%, >300 pg/ml (sugestivo de alto remodelamiento); y tan sólo 9.6% tuvieron PTH en los valores recomendados. Al comparar los valores pre y postrasplante, la creatinina sérica disminuyó en forma significativa, no hubo diferencia en el calcio sérico y fosfatasa alcalina, pero se encontró una disminución significativa en fósforo y magnesio. Doce pacientes (38.7%) presentaron hipofosfatemia postrasplante. Diez pacientes (32%) cursaron con hipomagnesemia. Todos incrementaron el valor z de peso en forma significativa. La función renal tuvo correlación positiva con el calcio sérico y negativa con el fósforo y el magnesio (p <0.05). Los niveles de tacrolimus tuvieron una correlación negativa con el magnesio sérico (r =-0.431, p <0.0001). Conclusiones. La velocidad de filtración glomerular al momento del trasplante tuvo una correlación negativa con el fósforo sérico basal y la concentración de tacrolimus, con el magnesio sérico. El crecimiento fue mejor en los pacientes que no presentaron hipofosfatemia durante el postrasplante. Es necesario vigilar y tratar oportunamente las alteraciones minerales en el postrasplante renal.

Background. Information regarding chronic kidney disease-mineral bone disorder (CKD-MBD) in children who undergo renal transplant is scarce. Despite successful renal transplantation, bone disorders have been described and attributed to immunosuppressive drugs (steroids and calcineurin inhibitors). Therefore, it is important to determine the prevalence and outcome of bone mineral disorders pre- and post-renal transplant. The aim was to describe the prevalence and type of bone mineral disorders in children pre-renal transplant and outcomes. Methods. The Institutional Review Board and Ethics Committee approved the study. Signed consent/assent was obtained from all participants. Patients <18 years of age and under investigation for a first renal transplant were invited to participate. At transplant and 6 and 12 months after transplantation, anthropometric data were collected and blood samples were collected for serum creatinine, slope levels of tacrolimus, serum calcium, phosphorus, magnesium and alkaline phosphatase. Intact parathyroid hormone (PTH) was measured before transplant. Results. Thirty-one patients were included with a mean age of 14.6 ± 3.2 years. Females represented 52%. All received induction with basiliximab and triple maintenance therapy with prednisone, mycophenolate mofetil and tacrolimus. Pre-transplant PTH values were <150 pg/ml in 51.6%, suggestive of low turnover bone lesions, 38.7% had PTH >300 pg/ml, suggestive of high turnover bone lesions and only 9.6% had PTH between 150 and 300 pg/ml. When pre- and post-transplant studied parameters were compared, serum creatinine was statistically lower during follow-up. No difference was found in serum calcium and alkaline phosphatase, but magnesium and phosphorus values were significantly lower after transplant. Twelve patients (38.7%) had post-transplant hypophosphatemia and required supplementation. Ten patients (32%) had hypomagnesemia, seven of them with concomitant hypophosphatemia. Z-score for weight increased significantly after renal transplant; nevertheless, only patients with no hypophosphatemia during follow-up improved their Z-score for height. Glomerular filtration rate had a positive correlation with serum calcium and a negative correlation with phosphorus and magnesium (p <0.05). Tacrolimus slope levels had a significantly negative correlation with serum magnesium (r =-0.431, p <0.0001). Conclusions. Glomerular filtration rate had a negative correlation with serum phosphorus at transplant. Tacrolimus slope levels had a negative correlation with magnesium serum values. Patients with no hypophosphatemia during the first year had better growth than those with hypophosphatemia. It is important to monitor and opportunely treat bone mineral disorders in children who undergo transplantation.

Efeitos endócrinos e metabólicos das drogas antiepilépticas / Endocrine and metabolic effects of antiepileptic drugs

As drogas antiepilépticas (DAE) são utilizadas por um enorme contingente de pessoas em todo o mundo - tanto no tratamento das epilepsias como para outros fins - frequentemente por um longo tempo. Por essas razões, torna-se fundamental o conhecimento sobre os potenciais efeitos adversos desses medicamentos, muitos deles envolvendo vários aspectos hormonais e metabólicos que devem ser do conhecimento do endocrinologista. Nesta revisão, foi abordada a relação das DAE com anormalidades no metabolismo mineral ósseo, balanço energético e peso corporal, eixo gonadal e função tireoideana, além de ter sido revisado o papel terapêutico dessas medicações no tratamento da neuropatia diabética.

The antiepileptic drugs (AED) have been widely used for a great deal of people - in the treatment of epilepsy and other diseases - throughout the world. Continuous and prolonged use of AED may be associated with adverse effects in different systems, including a variety of endocrine and metabolic abnormalities. In this review, the relationship of AED with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism was revised, as well as their clinical utility in the treatment of diabetic neuropathy.

Relationship between serum osteoprotegerin levels and bone mineral metabolism in women / 대한내과학회지

BACKGROUND: Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the RANK ligand. OPG has been shown to be an important inhibitor of osteoclastogenesis in animal models. The relationship between circulating OPG levels and female bone status in human populations is unclear. Thus, the aim of this study was to investigate the relationship between circulating OPG levels and bone mineral metabolism in Korean women. METHODS: ubjects were 287 women aged 37~73 (mean age, 51.5 yr). Serum concentrations of OPG were determined by ELISA. Biochemical markers of bone turnover and follicle stimulating hormone (FSH) were measured by standard methods. Bone mineral density at lumbar spine and femur neck were measured by dual energy X-ray absorptiometry. RESULTS: e observed a significant positive association between circulating OPG levels and urine calcium excretion (r=0.128; p<0.05). Although circulating OPG levels were not significantly correlated to urine deoxypyridinoline levels (r=0.105; p=0.076), but there was a weak trend in it. We found that mean OPG levels were about 11% greater in postmenopausal women (mean +/- SD, 1358.5 +/- 380.0 pg/mL) than in premenopausal women (1228.8 +/- 407.7 pg/mL; p<0.001). There was a significant positive relationship between circulating OPG levels and serum FSH levels (r=0.172; p<0.01). There was a non-significant relationship between circulating OPG levels and bone mineral density at lumbar spine and femur neck. CONCLUSION: In conclusion, our data shows that the circulating OPG levels are associated with urine calciumexcretion and serum FSH levels in Korean women. These data suggest that OPG may be an important paracrine mediator of female bone metabolism in human populations.

Relationship between Serum Osteoprotegerin-Receptor Activator of NF-kappaB Ligand Levels and Bone Mineral Metabolism in Men / 대한내분비학회지

BACKGROUND: Osteoporosis is a growing health problem, not only in women, but in men also. Sex hormones and insulin-like growth factor-I (IGF-I) have been shown to be the major determinant in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine, which acts as a decoy receptor for the receptor activator of the NF- B ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis in animal models. The relationship between the OPG-RANKL system and male bone status in human populations is unclear. The aim of this study was to investigate the relationship between circulating the OPG-RANKL system and bone mineral metabolism in 80 Korean men. METHODS: The subjects of this study were 80 men aged between 42 and 70 (mean age, 54.5 yr). The serum concentrations of OPG and RANKL were measured by ELISA. The serum concentrations of estradiol, total testosterone, IGF-I and biochemical markers of bone turnover were measured by standard methods. The bone mineral densites (BMD) at the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry. RESULTS: A significant correlation was observed between the serum OPG/RANKL ratios and osteocalcin levels (r=-0.229, p<0.05). The serum OPG levels were significantly correlated to the femoral neck BMD (r=-0.227, p<0.05). The mean value of the serum OPG was found to be greater in patients with osteoporosis at the femoral neck (mean SD, 4.72.1 pmol/L) than in subjects with a normal BMD (3.30.9 pmol/L, p<0.05). The serum RANKL/OPG ratios were significantly positively correlated to the serum estradiol level (r=0.401, p<0.001). Also, there was a significant negative correlation between the serum OPG and estradiol levels (r=-0.288, p<0.05). In a multiple regression analysis, the BMI, serum OPG and RANKL levels, and the serum IGF-I level were identified as significant predictors of the femoral neck BMD. In another multiple regression analysis, only the serum estradiol level was identified as a significant predictor of the serum OPG level. CONCLUSION: In conclusion, our data show that the serum OPG and RANKL levels are partly associated with bone mineral metabolism, and are related to the endogenous estrogen levels in human male populations. Therefore, the possibility exists that the OPG-RANKL system may be a mediator of the estradiol in male bone metabolism. However, there have been few study published on the relation between the serum OPG and estradiol levels in men. Further studies are needed to clarify this relationship

Relationship between Serum Osteoprotegerin-Receptor Activator of NF-kappaB Ligand Levels and Bone Mineral Metabolism in Men / 대한내분비학회지

BACKGROUND: Osteoporosis is a growing health problem, not only in women, but in men also. Sex hormones and insulin-like growth factor-I (IGF-I) have been shown to be the major determinant in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine, which acts as a decoy receptor for the receptor activator of the NF- B ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis in animal models. The relationship between the OPG-RANKL system and male bone status in human populations is unclear. The aim of this study was to investigate the relationship between circulating the OPG-RANKL system and bone mineral metabolism in 80 Korean men. METHODS: The subjects of this study were 80 men aged between 42 and 70 (mean age, 54.5 yr). The serum concentrations of OPG and RANKL were measured by ELISA. The serum concentrations of estradiol, total testosterone, IGF-I and biochemical markers of bone turnover were measured by standard methods. The bone mineral densites (BMD) at the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry. RESULTS: A significant correlation was observed between the serum OPG/RANKL ratios and osteocalcin levels (r=-0.229, p<0.05). The serum OPG levels were significantly correlated to the femoral neck BMD (r=-0.227, p<0.05). The mean value of the serum OPG was found to be greater in patients with osteoporosis at the femoral neck (mean SD, 4.72.1 pmol/L) than in subjects with a normal BMD (3.30.9 pmol/L, p<0.05). The serum RANKL/OPG ratios were significantly positively correlated to the serum estradiol level (r=0.401, p<0.001). Also, there was a significant negative correlation between the serum OPG and estradiol levels (r=-0.288, p<0.05). In a multiple regression analysis, the BMI, serum OPG and RANKL levels, and the serum IGF-I level were identified as significant predictors of the femoral neck BMD. In another multiple regression analysis, only the serum estradiol level was identified as a significant predictor of the serum OPG level. CONCLUSION: In conclusion, our data show that the serum OPG and RANKL levels are partly associated with bone mineral metabolism, and are related to the endogenous estrogen levels in human male populations. Therefore, the possibility exists that the OPG-RANKL system may be a mediator of the estradiol in male bone metabolism. However, there have been few study published on the relation between the serum OPG and estradiol levels in men. Further studies are needed to clarify this relationship

The relationship between urinary sodium excretion and bone mineral metabolism of climacteric women in Korea / 대한내과학회지

BACKGROUND: High oral intake of sodium is known to increase urinary calcium excretion in hypercalciuria and renal-stone formers, and there is well-documented correlation between urinary sodium and calcium excretion in 24-hour urine collections from normal subjects and postmenopausal women. The present study was aimed to investigate relationship between urinary sodium excretion and bone mineral metabolism of climacteric women in Korea. METHODS: We measured 24-hour urinary sodium, calcium, and creatinine level; serum osteocalcin level, serum alkaline phosphatase (ALP) level, serum follicular stimulating hormone (FSH) level; urine deoxypyridinoline (DPD) level; and bone mineral density (BMD) in 430 climacteric women in Korea (331 postmenopausal and 99 premenopausal women). RESULTS: The postmenopausal women had higher (p<0.05) value for mean urinary sodium to creatinine ratio of 0.225+/-0.078 mmol/mg vs. 0.209+/-0.061 mmol/mg and higher (p<0.001) value for mean urinary calcium to creatinine ratio of 0.261+/-0.125 mg/mg vs. 0.209+/-0.081 mg/mg than the premenopausal women. Significant positive correlation was noted between urinary sodium to creatinine ratio and urinary calcium to creatinine ratio (r=0.426, p<0.001). Negative correlation was found between urinary sodium to creatinine ratio and femur neck BMD (r=-0.099, p<0.05). Although urinary sodium to creatinine ratio was not significantly correlated to serum FSH level (r=0.066, p=0.088), serum ALP level (r=0.067, p=0.083), urine DPD level (r=0.077, p=0.056), and lumbar BMD (r=-0.067, p=0.083), but there is a weak trend in it. CONCLUSION: There is not only an increase in urinary sodium excretion at postmenopausal women, but also an increase in the urinary calcium excretion. It seems that subjects with a high urinary sodium excretion show a higher urinary calcium excretion that may have some effect on bone mineral metabolism. However, further studies are required to establish whether urinary sodium excretion have a direct effect on bone mineral metabolism of climacteric women in Korea.