Bone, fat, and muscle interactions in health and disease

Abstract Energy metabolism is a point of integration among the various organs and tissues of the human body, not only in terms of consumption of energy substrates but also because it concentrates a wide interconnected network controlled by endocrine factors. Thus, not only do tissues consume substrates, but they also participate in modulating energy metabolism. Soft mesenchymal tissues, in particular, play a key role in this process. The recognition that high energy consumption is involved in bone remodeling has been accompanied by evidence showing that osteoblasts and osteocytes produce factors that influence, for example, insulin sensitivity and appetite. Additionally, there are significant interactions between muscle, adipose, and bone tissues to control mutual tissue trophism. Not by chance, trophic and functional changes in these tissues go hand in hand from the beginning of an individual's development until aging. Likewise, metabolic and nutritional diseases deeply affect the musculoskeletal system and adipose tissue. The present narrative review highlights the importance of the interaction of the mesenchymal tissues for bone development and maintenance and the impact on bone from diseases marked by functional and trophic disorders of adipose and muscle tissues. Arch Endocrinol Metab. 2022;66(5):611-20

El déficit de vitamina D en pacientes con espondiloartritis en un hospital de Castilla-La Mancha / Vitamin D deficiency in patients with spondylarthritis in a Spanish (Castilla-La Mancha) hospital

RESUMEN Introducción: Las espondiloartritis son un grupo de enfermedades inflamatorias crónicas con afectación principalmente del esqueleto axial y también de articulaciones periféricas. En cuanto al metabolismo óseo de estos pacientes, se ha observado en algunos estudios que existen niveles más bajos de vitamina D en pacientes con espondiloartritis. Objetivo: Estimar la prevalencia de déficit/insuficiencia de vitamina D, el metabolismo fosfocálcico y sus implicaciones en una cohorte de pacientes con espondiloartritis. Metodología: Estudio observacional, descriptivo y transversal. Se llevó a cabo una revisión retrospectiva de la base de datos de pacientes con espondiloartritis que fueron atendidos en las consultas externas del Servicio de Reumatología del Hospital General Universitario de Ciudad Real entre junio del 2018 y junio del 2019. Las variables se describieron usando medidas de frecuencia o medidas de tendencia central/dispersión según correspondiera. Resultados: Se analizaron 115 pacientes, de los cuales 64 fueron hombres y 51 mujeres, con una edad media de 45,97 años (± 13,41 DE). Del total de los pacientes, 59 presentaron espon dilitis anquilosante, 24 artropatía psoriásica, 9 artritis asociada a enfermedad inflamatoria intestinal, 12 espondiloartritis axial no radiográfica y 11 artritis reactiva. Los niveles de vitamina D fueron de 23,81 ng/ml (±10,5 DE), con un 77,4% de los pacientes con cifras de déficit/insuficiencia de vitamina D. Agrupados por el subtipo de espondiloartritis y según las cifras de déficit/insuficiencia de vitamina D, 45 pacientes tenían espondilitis anquilo sante, 19 artropatía psoriásica, 9 artritis asociada a enfermedad inflamatoria intestinal, 7 espondiloartritis axiales no radiográficas y 9 artritis reactivas. Además, el déficit de vita mina D (< 20 ng/ml) se presentaba la mayoría de las veces en las estaciones de primavera e invierno, con 31 y 26 pacientes respectivamente. Conclusiones: Una optimización de los niveles de vitamina D puede implicar una mejoría en la situación clínica del paciente, medida tanto por BASDAI y DAPSA como por PCR y VSG. En consecuencia, se recomienda la monitorización y suplementación de vitamina D en pacientes con hipovitaminosis D.

ABSTRACT Introduction: Spondyloarthritis is a group of chronic inflammatory diseases that mainly affect the axial skeleton, and also the peripheral joints. In bone metabolism studies on these patients, it has been observed that there are lower levels of vitamin D in patients with spondyloarthritis. Objective: To estimate the prevalence of vitamin D deficiency / insufficiency, as well as calcium/ phosphate metabolism and their implications in a cohort of patients with spondyloarthritis. Methodology: Observational, descriptive, and cross-sectional study. A retrospective review of the databases was carried out on patients with spondyloarthritis who were treated in the outpatient clinics of the Rheumatology Department of the General University Hospital of Ciudad Real between June 2018 and June 2019. Variables are described using frequency and central tendency / dispersion measurements as appropriate. Results: The study included 115 patients, of whom 64 were men and 51 women, with a mean age of 45.97 years (± 13.41 SD). They included 59 patients with ankylosing spondylitis, 24 with psoriatic arthropathy, 9 arthritis associated with inflammatory bowel disease, 12 non-radiographic axial spondylarthritis, and 11 reactive arthritis. Vitamin D levels were 23.81 ng/ml (± 10.5 SD), with 77.4% of patients with vitamin D deficiency / insufficiency levels. Grouped by the spondylarthritis subtype, and according to vitamin D deficiency / insufficiency, 45 patients had ankylosing spondylitis, 19 psoriatic arthropathy, 9 arthritis associated with inflammatory bowel disease, 7 non-radiographic axial spondyloarthritis, and 9 reactive arthritis. Furthermore, vitamin D deficiency (< 20 ng/ml) mainly occurred in the spring and winter seasons, with 31 and 26 patients, respectively. Conclusions: An optimization of vitamin D levels may lead to an improvement in the clinical situation of the patients, as measured by both BASDAI and DAPSA, as well as by PCR and ESR. Therefore, vitamin D monitoring and supplementation is recommended in patients with vitamin D deficiency.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up / Biomarcadores del metabolismo mineral óseo (FGF-23, fetuína-A) y calcificaciones vasculares como herramientas predictivas de muerte cardiovascular de pacientes en diálisis, a 10 años de seguimiento

Abstract Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary stud ies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Resumen Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad car diovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p<0.001). El mejor punto de corte fue de 5 (sensibili dad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Excess Calcium, Magnesium and Phosphorus Deposition in the Epigastric Artery of Dialysis Patients Undergoing Renal Transplantation

ABSTRACT Objective: Vascular calcification contributes to cardiovascular disease on dialysis patients. Arterial mineral content is modified but not well defined. We aim to define what is the concentration of calcium, magnesium and phosphorus in the epigastric artery of adult dialysis patients undergoing renal transplantation. Methods: All renal allograft recipients who underwent surgery at our centre between May 2003 and December 2005 and consented to be taken small samples of epigastric artery were included in our cross-sectional study. Histological, radiological and spectrometric methods were used to measure vascular calcification, deposits and concentrations of calcium, phosphorus and magnesium in epigastric artery, which were correlated with clinical and biochemical characteristics. Mineral vascular content was compared with corresponding samples from cadaveric renal donors free from renal disease (control group). Results: Calcium and magnesium concentrations in epigastric artery were much higher in recipients (n = 100) than in donors (n = 30). Histologically confirmed calcifications were more frequent in recipients. Calcium and magnesium content in epigastric artery were correlated directly with recipient age, pre-transplant serum P and Ca × P product. A high content of calcium and magnesium in this artery was observed in recipients with media and intimal calcification. Multivariate logistic regression showed that dialysis vintage > 3.5 years and calcium concentration in epigastric artery ≥ 4500 mg/kg wet weight were independent predictors of histological calcification. Conclusion: Excess mineral deposition is observed in the epigastric artery of dialysis patients, where the recipient's age, serum P, Ca × P product and time on dialysis play a decisive role.

In vitro anti-inflammatory effects of vitamin D supplementation may be blurred in hemodialysis patients

OBJECTIVES: This study aimed to evaluate the potential anti-inflammatory effects of vitamin D supplementation under uremic conditions, both in vivo and in vitro, and its effects on the parameters of mineral metabolism. METHODS: Thirty-two hemodialysis patients were randomly assigned to receive placebo (N=14) or cholecalciferol (N=18) for six months. Serum levels of calcium, phosphate, total alkaline phosphatase, intact parathyroid hormone (iPTH), and vitamin D were measured at baseline and after three and six months. The levels of fibroblast growth factor-23 (FGF-23), interleukin-1β (IL-1β), and high-sensitivity C-reactive protein (hs-CRP) were also measured at baseline and at six months. Human monocytes were used for in vitro experiments and treated with cholecalciferol (150 nM) and uremic serum. Cell viability, reactive oxygen species (ROS) production, and cathelicidin (CAMP) expression were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, dichloro-dihydro-fluorescein diacetate assay, and real time-quantitative polymerase chain reaction, respectively. RESULTS: Both patient groups were clinically and biochemically similar at baseline. After six months, the levels of vitamin D and iPTH were higher and lower, respectively, in the cholecalciferol group than in the placebo group (p<0.05). There was no significant difference between the parameters of mineral metabolism, such as IL-1β and hs-CRP levels, in both groups. Treatment with uremic serum lowered the monocyte viability (p<0.0001) and increased ROS production (p<0.01) and CAMP expression (p<0.05); these effects were counterbalanced by cholecalciferol treatment (p<0.05). CONCLUSIONS: Thus, cholecalciferol supplementation is an efficient strategy to ameliorate hypovitaminosis D in hemodialysis patients, but its beneficial effects on the control of secondary hyperparathyroidism are relatively unclear. Even though cholecalciferol exhibited anti-inflammatory effects in vitro, its short-term supplementation was not effective in improving the inflammatory profile of patients on hemodialysis, as indicated by the IL-1β and hs-CRP levels.

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.

Digital pressure in haemodialysis patients with brachial arteriovenous fistula

Background & objectives: The pathophysiological mechanisms involved in distal pressure changes following arteriovenous fistula (AVF) creation in patients with end-stage renal disease (ESRD) are not completely understood. This study was aimed to assess digital pressure changes post-AVF creation and to identify the factors that might influence these changes in ESRD patients. Methods: In this prospective study, 41 patients with ESRD underwent AVF creation. Basal digital pressure (BDP), digital brachial index (DBI), calcium, phosphorus and blood urea levels were assessed preoperatively. BDP, DBI, vein and artery diameters, and AVF blood flow were also evaluated at one and two month(s) post-AVF creation. Results: Mean BDP significantly decreased from 131.64±25.86 mmHg (baseline) to 93.15±32.14 and 94.53±32.90 mmHg at one and two months post-AVF creation, respectively (P <0.001). Mean DBI significantly decreased one month post-AVF creation versus baseline (0.70±0.18 vs. 0.89±0.17 mm, P <0.001) and remained similar at two versus one month(s) postoperatively (0.70±0.23 vs. 0.70±0.18 mm). At both postoperative timepoints, no correlation between DBI decrease and increased artery and vein diameters or fistula blood flow was observed. Mean DBI difference between patients with previous ipsilateral access versus those without was not significant from pre to one month postoperatively. No correlation was observed between baseline phosphorus, calcium and blood urea nitrogen and DBI changes. Interpretation & conclusions: Our findings suggest that decrease in distal pressure following AVF creation may not be influenced by the arterial remodelling degree, vein diameter or fistula flow. In uraemic patients, those with low calcium and/or increased phosphorus, no association between these parameters and DBI changes could be observed.

Research progress on serum magnesium disorder and its effects in patients with chronic kidney disease / 医学研究生学报

The effect of blood magnesium disorder on chronic kidney disease (CKD) has been gradually confirmed in recent years. At present, magnesium homeostasis depends on dietary intake, gastrointestinal absorption and kidney metabolism. In recent years, it has been proposed that the magnesium concentration of dialysate and the influence of drugs (especially proton pump inhibitors) on magnesium homeostasis cannot be ignored in the treatment of CKD patients. Although the mechanism of the effect of magnesium on CKD has not been fully elucidated, recent studies suggest that magnesium deficiency may aggravate hypertension and vascular calcification in CKD patients, affecting mineral metabolism, leading to increased mortality. The application of different magnesium-based binders, such as magnesium citrate, calcium acetate/magnesium carbonate, and magnesium oxide, can help to alleviate the effect of low magnesium levels on CKD, which needs further research.

¿podemos hablar hoy de un valor de fósforo como indicador de la calidad del tratamiento dialítico? / Can we speak today of a phosphorus value as an indicator of dialysis treatment quality?

Introducción: El trastorno del metabolismo óseo y mineral constituye una grave complicación de la insuficiencia renal crónica. Respecto al fósforo, las nuevas Guías KDIGO sugieren disminuir la hiperfosfatemia, sin recomendar un valor determinado. Sin embargo, en Argentina se utiliza como indicador de calidad dialítica (IndCalDial) un valor de fósforo igual o inferior a 5 mg/dL. Nuestro objetivo fue evaluar si dicho objetivo es actualmente válido como IndCalDial. Material y métodos: Estudio multicéntrico, de corte transversal. Se incluyeron pacientes mayores de 18 años, con más de 90 días en hemodiálisis. Se tabularon datos demográficos y de laboratorio, comparándose normofosfatémicos contra hiperfosfatémicos. Según el método, en 3 centros el límite superior de referencia fue 4.5 mg/dL y en cuatro 5.6 mg/dL, éstos últimos se analizaron como grupo separado F 5.6. Resultados: Se incluyeron 333 pacientes. Edad, sexo, porcentaje FAV, diabéticos, tiempo en diálisis, Kt/V, Hemoglobina y Albumina, fueron semejantes a los datos del registro. La mediana de fosfatemia fue 5.2 mg/dL, (rango: 2.3 a 10.6). Los pacientes hiperfosfatémicos presentaron menor edad, menos tiempo en diálisis y cifras mayores de hemoglobina y Albumina. En el grupo F 5.6 (n = 203), según KDIGO sólo el 33.7 % necesitaría tratamiento. De aplicarse el IndCalDial (fósforo menor a 5 mg/dL), el porcentaje sería de 55%, es decir, un 21.3% de pacientes normofosfatémicos deberían ser tratados. Conclusiones: Debería estandarizarse la determinación de fosfatemia, previo a utilizar un valor fijo como IndCalDial.

Introduction: Bone and mineral metabolism disorder is a serious complication of Chronic Kidney Disease. Concerning phosphorus, the new KDIGO Guidelines suggest a reduction of hyperphosphatemia, but they do not recommend a specific value. However, in Argentina, a phosphorus value of 5 mg/dL or less is used as a dialysis quality indicator (DiaQualInd). Our objective was to evaluate whether this goal is currently valid as a DiaQualInd. Methods: A multicentric, cross-sectional study was conducted. Patients older than 18 were included, with more than 90 days undergoing hemodialysis. Demographic and laboratory data were tabulated, comparing normophosphatemic with hyperphosphatemic values. According to this method, in 3 centers the upper reference limit was 4.5 mg/dL and in 4 centers it was 5.6 mg/dL. The latter were analyzed as a separate group (F 5.6). Results: There were 333 patients included in this study. Age, sex, AVF percentage, diabetes, time on dialysis, Kt/V, hemoglobin and albumin were similar to the registry data. The median phosphatemia was 5.2 mg/dL, (range: 2.3 to 10.6). The hyperphosphatemic patients were the youngest, spent less time on dialysis and showed higher hemoglobin and albumin values. In group F 5.6 (n = 203), according to KDIGO only 33.7% would need treatment. If this DiaQualInd were to be applied (phosphorus lower than 5 mg/dL), the percentage would be 55%, that is, 21.3% of normophosphatemic patients should be treated. Conclusions: Phosphatemia determination should be standardized before using a fixed value such as DiaQualInd

¿Puede establecerse hoy un valor de fosfatemia como indicador de calidad del tratamiento dialítico? / Can a phosphatemia value be established today as an indicator of the quality of the dialysis treatment?

INTRODUCCIÓN: El trastorno del metabolismo óseo y mineral constituye una grave complicación de la IRC. Respecto al fósforo, las nuevas Guías KDIGO sugieren disminuirla hiperfosfatemia, sin recomendar un valor determinado. Sin embargo, en Argentina se continúa utilizando como indicador de calidad dialítica (IndCalDial) un valor de fósforo igual o inferior a 5 mg.dl. Nuestro objetivo fue evaluar si un valor fijo de fosfatemia es válido como IndCalDial. MATERIAL Y MÉTODOS: Se realizó un estudio multicéntrico, de corte transversal. Se incluyeron pacientes mayores de 18 años, con más de 90 días en hemodiálisis crónica. Se tabularon datos demográficos y de laboratorio. Según el reactivo empleado en la determinación de fósforo, en 4 centros el límite superior de referencia fue 4.5 mg.dl (Grupo F4.5) y en tres 5.6 mg.dl (Grupo F5.6). RESULTADOS: Se incluyeron 334 pacientes. Edad, sexo, porcentaje con FAV, diabéticos, tiempo en diálisis, Kt/V, Hemoglobina y Albúmina, resultaron semejantes a los del Registro Nacional de Diálisis. La mediana de fosfatemia fue 5.2 mg.dl, (rango: 2.3 a 10.6). Los pacientes hiperfosfatémicos fueron más jóvenes y presentaron mejores niveles de Albúmina. De considerarse como IndCalDial: Fósforo menor a 5 mg.dl, 21 pacientes del Grupo F4.5 (n=154) con fosfatemia entre 4.5 y 5.0 mg.dl no recibirían tratamiento, mientras que en el Grupo F5.6 (n=180), 32 pacientes con fosfatemia entre 5.1 y 5.6 mg.dl deberían recibir tratamiento, a pesar de presentar normofosfatemia. CONCLUSIONES: Debería estandarizarse la determinación de fosfatemia, previo a utilizar un valor fijo como IndCalDial

Correlation of fibroblast growth factor 23 with adverse prognosis of chronic kidney disease and therapy strategy / 中南大学学报(医学版)

Fibroblast growth factor 23 (FGF23) is a hormone secreted by the bone.It is not only involved in the pathophysiological process of chronic kidney disease (CKD),but also associated with the poor prognosis.In patients with CKD,serum FGF23 levels are elevated in early phase.The increased FGF23 levels gradually lead to myocardial hypertrophy,inflammatory,vascular calcification,and low level of vitamin D,which contribute to the progress of CKD,cardiovascular complications and even death.Presently,there are several ways to reduce FGF23 levels,including decrease of intake and block of phosphorus absorption,supplement of FGF23 antibody and pseudo calcium or renal transplantation

Hipomagnesemia subclínica em vacas leiteiras durante o período de transição: ocorrências hormonais e metabólicas / Subclinic hypomagnesemia in dairy cows during transiton period: hormonal and metabolic events

O objetivo, com este estudo, foi investigar as conseqüências da hipomagnesemia subclínica sobre parâmetros metabólicos de vacas leiteiras. Amostras de sangue foram coletadas de 12 animais, a cada dois dias, entre os dias 22 pré e 22 pós-parto, para a realização de análises sanguíneas e determinação do perfil metabólico. Os animais foram categorizados de acordo com os níveis séricos de magnésio: Grupo Hipomagnesêmicas (n=5), com níveis abaixo de 1,8 mg/dL em ao menos dois dias consecutivos, e o Grupo Controle (n=7), com níveis acima de 1,8 mg/dL em todo o período. O grupo hipomagnesêmicas apresentou níveis de glucagon maiores nos dias 10, 18 e 20, e a taxa Glucagon/Insulina foi maior nos dias 6, 8, 10, 12 e 16 após o parto. As concentrações de aspartato amino transferase foram maiores no grupo hipomagnesêmicas nos dias 0, 6, 8, 10, 12 e 14 pós-parto. Os resultados indicaram que níveis reduzidos de magnésio no periparto podem estar relacionados com níveis elevados de aspartato amino transferase e de glucagon. Em geral, a hipomagnesemia subclínica não altera os níveis dos indicadores do metabolismo energético, mas os resultados demonstraram que as vacas com hipomagnesemia apresentaram maior taxa de glucagon/insulina, demonstrando um maior desafio para manter os níveis glicêmicos.

The objetctive, with this study, was to investigate the consequences of subclinical hypomagnesemia on the metabolic parameters of dairy cows. Blood samples were collected from 12 animals every two days, between -22 pre and 22 days postpartum, for blood analysis and determining the metabolic profile. The animals were grouped according to magnesium blood concentrations: Hypomagnesemia group (n=5), with blood levels below 1.8 mg/dL in at least two consecutive days, and Control group (n=7), with blood levels above 1.8 mg/dL during the period. The hypomagnesemia group had higher levels of glucagon on days 10, 18 and 20 as well as glucagon/insulin ratio was higher on 6, 8, 10, 12 and 16 days after calving. The blood concentrations of aspartate aminotransferase in the hypomagnesemia group were higher during days 0, 6, 8, 10, 12 and 14 after calving. The results indicate that the low blood levels of magnesium during peripartum may be associated with elevated levels of aspartate amino transferase and glucagon in the blood. In general, subclinical hypomagnesemia does not alter the levels of indicators of energy metabolism, but the results show that cows with hypomagnesemia have a higher rate of glucagon/insulin, demonstrating a greater challenge to maintain glucose blood concentration.

Clinical research on changes of mineral and bone metabolism before and after renal transplantation / 中华器官移植杂志

Objective To explore the changes of mineral and bone metabolism before and after renal transplantation as well as the effect of preoperative parathyroid hormone (PTH) level on postoperative mineral and bone metabolism.Methods In this retrospective analysis,we recruited 82 cases of renal transplant recipients with normal renal function and receiving kidney transplantation in our hospital from January 2011 to January 2015.All of these patients had intact PTH (iPTH) level ＞300 pg/mL.We chose 26 cases of recipients whose preoperative iPTH was more than or equal to 800 pg/mL as very high PTH group,and 56 cases of recipients whose preoperative iPTH was between 301-799 pg/mL as high PTH group.We monitored and performed analysis of the total serum calcium (Ca),serum inorganic phosphorus (P),25-(hydroxyl) vitamin D3 (25 OHD),serum alkaline phosphatase (ALP),Beta C-terminal telopeptide (β-CTX),N-terminal/midregion (N-MID) pre-and 1 month,4 months,1 year,2 years,3 years post-kidney transplantation.Results Serum total calcium in the two groups was gradually increased,returned to normal range 1 month post-transplantation and reached the plateau 4 months post-transplantation.The incidence of hypercalcemia in very high PTH group was statistically significantly higher than in high PTH group.Serum phosphorus in the two groups showed a trend of gradual decline after renal transplantation,and returned to the normal range 1 month post-transplantation.The serum phosphorus level in very high PTH group reached the plateau 4 months post-transplantation,and that in high PTH group 1 month post-transplantation.Compared with high PTH group,very high PTH group has greater The incidence of long-term hypophosphatemia after renal transplantation was significantly higher in very high PTH group then in high PTH group.iPTH,ALP,β-CTX and N-MID in the two groups showed a downward trend after renal transplantation.At first month post-transplantation,iPTH,ALP,β-CTX and N-MID levels were reduced most significantly.The average levels of the three mentioned indicators in very high PTH group were higher than in high PTH group at every time point after surgery with the difference being significant during the early post-transplantation period.The anomalies of iPTH and β-CTX levels persisted to long term after transplantation in very high PTH group.25-OHD levels in these two groups showed rising trend after renal transplantation,reached the plateau 4 months posttransplantation,but failed to achieve the ideal reference level,and no significant difference was found between two groups at any time point monitored.Conclusion The anomalies of mineral and bone metabolism after renal transplantation could persist a long time.Conclusion hyperparathyroidism in the renal transplantation plays an important role in mineral and bone metabolism.Preoperative severe HPT could continue to post-transplantation period and increase the incidence of hyperphosphatemia and hypocalcemia long term after transplantation,which may aggravate bone turnover and this effect can last a long time after transplantation.

Correlation between quality of life and mineral metabolism in maintenance hemodialysis patients / 中华肾脏病杂志

Objective With multi?center investigation, to assess the life quality of patients with maintained hemodialysis (MHD) in Liaoning Province and to explore the relationship among the mineral metabolism, the life quality of the patients with MHD, and the repeated hospitalization within the latest three years. Methods 1192 patients with hemodialysis (at least 3 months) from January to March in 2015 at ten blood purification centers in Liaoning Province were selected for the cross?————————sectional survey. The Kidney Health?related Quality of Life (HRQOL) version 1.3 was used to evaluate the MHD patients' life quality. The total length of hospitalization was divided into four groups: 0 days, 3 to 15 days, 16 to 30 days and above 30 days. Results When serum calcium value ranged from 2.1 to 2.5 mmol/L, kidney?disease component summary (KDCS), mental component summary (MCS), physical component summary (PCS) and SF?36+KDCS corresponded to a higher value (P<0.05). When serum phosphorus value ranged from 1.13 to 1.78 mmol/L, KDCS and SF?36+KDCS corresponded to a higher value (P<0.05). When the calcium phosphorus product value ranged from 40.68 to 49.94, MCS corresponded to a higher value (P<0.05). KDCS showed a linear correlation with age (P<0.001), dialysis age, serum calcium (less than or equal to 2.5 mmol/L) (P<0.05); PCS showed a linear correlation with age (P<0.001) and dialysis age (P<0.05); SF?36+KDCS showed a linear correlation with age (P<0.001), and serum calcium (less than or equal to 2.5 mmol/L) (P<0.05), while age and dialysis age were negatively correlated. The hospitalization days showed a linear correlation with age, dialysis age (P<0.001) and serum phosphorus, calcium phosphorus product value (P<0.05), while dialysis age and calcium phosphorus product value were negatively correlated. Among different groups of total hospitalization days in three years, age, hemodialysis age, serum calcium, serum phosphorus, calcium?phosphorus product value and quality of life values were all statistically significant (P<0.05). Conclusions The life quality of patients with MHD were correlated with serum calcium, phosphorus, calcium and phosphorus product value, iPTH, dialysis age and age, while age and dialysis age were of negative correlation. The total number of hospitalization days in 3 years was closely linearly correlated with age and dialysis age, significantly correlated with serum phosphorus, calcium and phosphorus product value, while dialysis age, calcium and phosphorus product value were in a negative correlation. The total number of hospitalization in 3 years was correlated with the patients' age, dialysis age, serum calcium, serum phosphorus, calcium and phosphorus product value and quality of life.

Protective effect of dietary chitosan on cadmium accumulation in rats

BACKGROUND/OBJECTIVES: Cadmium is a toxic metal that is an occupational and environmental concern especially because of its human carcinogenicity; it induces serious adverse effects in various organs and tissues. Even low levels of exposure to cadmium could be harmful owing to its extremely long half-life in the body. Cadmium intoxication may be prevented by the consumption of dietary components that potentially reduce its accumulation in the body. Dietary chitosan is a polysaccharide derived from animal sources; it has been known for its ability to bind to divalent cations including cadmium, in addition to other beneficial effects including hypocholesterolemic and anticancer effects. Therefore, we aimed to investigate the role of dietary chitosan in reducing cadmium accumulation using an in vivo system. MATERIALS/METHODS: Cadmium was administered orally at 2 mg (three times per week) to three groups of Sprague-Dawley rats: control, low-dose, and high-dose (0, 3, and 5%, respectively) chitosan diet groups for eight weeks. Cadmium accumulation, as well as tissue functional and histological changes, was determined. RESULTS: Compared to the control group, rats fed the chitosan diet showed significantly lower levels of cadmium in blood and tissues including the kidneys, liver, and femur. Biochemical analysis of liver function including the determination of aspartate aminotransferase and total bilirubin levels showed that dietary chitosan reduced hepatic tissue damage caused by cadmium intoxication and prevented the associated bone disorder. CONCLUSIONS: These results suggest that dietary chitosan has the potential to reduce cadmium accumulation in the body as well as protect liver function and bone health against cadmium intoxication.

Asociaciones entre nefrolitiasis, citrato y otros metabolitos presentes en orina y suero de pacientes / Associations between nephrolithiasis, citrate and other metabolites in urine and serum of patients

Objetivo: determinar las asociaciones entre nefrolitiasis citrato y otros metabolitos presentes en orina y suero de pacientes con el objeto de adecuar el diagnóstico en los protocolos de atención de la nefrolitiasis. Materiales y métodos: investigación descriptiva, transversal y de campo que incluyo sujetos con nefrolitiasis sin tratamiento con tiazidas, la muestra quedó conformada por 100 pacientes a quienes se realizó evaluación metabólica en orina de 24 horas y en muestras de suero sanguíneo. A los datos se les aplico estadísticos descriptivos y de dispersión y se compararon las frecuencias de las variables con Chi-cuadrado. Resultados: 93% de los pacientes con litiasis tenían hipocitraturia. La hipernatresiuria se presentó en 71,0%, la hipercloremia en 59,1%, las asociaciones más frecuentes fueron la hipercloremia mas hipernatruremia (50,5%) y la hiperuricosuria + hipernatruria (30,1%). Conclusiones: existe alta prevalencia de hipocitraturia en individuos con nefrolitiasis; la patología se puede presentar sola o asociada con hasta tres anormalidades bioquímicas de orina y suero; la hipercloremia mas la hipermagnesemia es el único dúo de factores sanguíneos que caracteriza al paciente con nefrolitiasis e hipocitraturia; y es frecuente la combinación de alteraciones de parámetros urinarios y de suero en hipocitraturia con nefrolitiasis.

Objective: to determine the associations between nephrolithiasis, citrate and others metabolites present in urine and serum ofpatients with the objective of adapting the diagnosis in care protocols nephrolithiasis. Materials and Methods: descriptive, transversal investigation that included subjects with nephrolithiasis without thiazide therapy, the sample was composed of 100 patients who metabolic evaluation was performed in 24-hour urine and blood serum samples. The dates were applied descriptive statistics and frequency dispersion and it's compared the frequency of variables with Chi-square. Results: 93% of patients with lithiasis had hypocitraturia. The hypernatresiuria occurred in 71.0%, 59.1% had hyperchloremia, the most frequent associations were the hypernatruremia hyperchloremia (50.5%) and hyperuricosuria + hypernatruria (30.1%). Conclusions: exist a high prevalence of hypocitraturia in patients with nephrolithiasis; the condition can occur alone or associated with urine biochemical abnormalities blood serum; hyperchloremia more hypermagnesemia is the only duo blood factors that characterize the patient with nephrolithiasis and hypocitraturia; and often a combination of alteration urine parameter and blood serum in patients with nephrolithiasis.

Evaluación del metabolismo fosfo-cálcico en el síndrome nefrófico córtico-sensible primario en pediatría / Evaluation of bone and mineral metabolism in primary corticosteroid-sensitive pediatric nephrotic syndrome

Introducción: el tratamiento esteroide del síndrome nefrótico cortico sensible (SNCS) puede causar alteraciones del metabolismo mineral, prevenibles con calcio y vitamina D. Se llevó a cabo un estudio de cohortes de tipo retrospectivo longitudinal a lo largo de 36 meses. Objetivos: 1) evaluar la relación entre la Dosis Acumulativa de corticoides (DAC) con la concentración sérica de 25-OH Vitamina D y con el Contenido Mineral Ëseo (CMO); 2) evaluar la relación entre la DAC y el CMO en la Densitometría Mineral Ësea (DMO). Material y métodos: Incluimos a pacientes entre 2 años y 12 años con síndrome nefrótico primario cortico-sensible (SNCS) (primer episodio o síndrome nefrótico recaedor o síndrome nefrótico cortico-dependiente), normotensos, eutróficos y con FG>90ml/min/1.73m2, los cuales se separaron en 3 grupos: GRUPO A: 3 o 6 años (puntaje Z y CMO), edad ósea, PTHi. Resultados: Evaluamos a 29 pacientes, con una edad media de 4,4 años. La DMO se realizó en 11 pacientes y no hubo diferencias significativas entre los grupos (p=0,08). Tampoco hubo diferencias significativas entre la media de la edad cronológica y la edad ósea media media (p 0,3). La prueba T para evaluar la dosis de 25-OH colecalciferol al aumentar la dosis de Ergocalciferol fue significativa (T:32.4 Q: <0.001). Hubo una correlación significativa entre los tres grupos: entre la dosis de Vitamina D y el dosaje sérico de Vitamina D de 0,9; entre el DAC y la dosis de 25 OH colecalciferol de 0,62 y entre el DAC y el CMO de 0.44. Por último, el aumento promedio en los tres grupos de dosis de vitamina D fue de 1833UI. Conclusiones: Observamos una relación entre la DAC e hipovitaminosis D, corregible al aumentar la dosis de Vitamina D.

Introduction: steroid treatment for corticosteroid-sensitive nephrotic syndrome (CSNS) could cause bone and mineral metabolism alterations, preventable with calcium and Vitamin D. Objectives: We carried out a preliminary retrospective study along 36 months with the following objectives. 1) To evaluate the relationship between Cumulative Corticosteroid Doses (CCD) and 25-0 Vitamin D serum concentration and with Bone Mineral Content (BMC); 2) To evaluate the relationship between CCD and Bone Mineral Densitomety (BMD). Methods: We included patients between 2 and 12 years of age with corticosteroid sensitive primary nephrotic syndrome (CSNS) (first episode, relapsing nephrotic syndrome, corticosteroid dependent nephrotic syndrome) normotensive, eutrophic and FG>:90ml/min/1.73 m2, who were divided into three groups: GROUP A: =3 or 4 relapses/year, GROUP C: CSNS, we measured: a) Quarterly: calcemia, phosphatemia, alkaline phosphatase; b) half-yearly: 25-OH cholecalcipherol levels, CCD; c) annually BMD in children >6 years (score Z and BMC), bone age, PTHi. Results: We evaluated 29 patients, average age: 4.4 years. The BMD was performed on 11 patients and there were no significant differences among the groups (p=0.08). No significant differences were seen between chronologic age and average bone age (p=0.3). Change in 25-OH cholecalcipherol levels due to the increase of ergocalcipherol dose was significant (T:32.4 Q:<0.001). There were significant correlation in the three groups, between Vitamin D dose and Vitamin D serum levels (Pearson correlation R=0.9), between CCD and 25 OH cholecalcipherol dose: (Pearson correlation R=0.62) and between CCD and BMC (Pearson correlation R=0.44). Finally, in these three groups the average increase of vitamin D was: 1833IU. Conclusions: We found a relationship between CCD and hypovitaminosis D, which could be corrected increasing Vitamin D dose.

Evaluation of parathyroid function and mineral metabolism in psychiatric patients using lithium salts / Avaliação da função paratireoidiana e metabolismo mineral em pacientes psiquiátricos usuários de sais de lítio

Objective: To evaluate parathyroid function and mineral metabolism in psychiatric patients users of lithium salts. Materials and methods: We measured the serum levels of calcium, ionized calcium, inorganic phosphorus, alkaline phosphatase, albumin, parathyroid hormone (PTH), urea, creatinine, 25-hydroxy-vitamin D and lithium of 35 patients diagnosed with bipolar disorder in use of lithium carbonate (LC) for at least one year (Lithium Group – LG) and 35 healthy subjects (Control Group – CG). Results: The LG and CG were matched by sex and age. There was only statistic difference in relation to the levels of PTH and ionized calcium, with p < 0.004 and p < 0.03, respectively. Secondary form of hyperparathyroidism (HPT) was found in eight (22.8%) LG patients and in none of the CG. There was no correlation between lithemia, usage time and dosage of LC. Conclusion: Our data demonstrate that lithium may create an imbalance in the parathyroid axis, characterized by elevated levels of PTH. .

Objetivo: Avaliar a função paratireoidiana e o metabolismo mineral em pacientes psiquiátricos usuários de sais de lítio. Materiais e métodos: Foram avaliados os níveis séricos de cálcio total, cálcio iônico, fósforo inorgânico, fosfatase alcalina, albumina, paratormônio (PTH), ureia, creatinina, 25-hidroxivitamina D e lítio de 35 pacientes diagnosticados com transtorno afetivo bipolar usuários de carbonato de lítio (CL) há pelo menos um ano (Grupo Lítio – GL) e 35 indivíduos saudáveis (Grupo Controle – GC). Resultados: O GL e o GC foram pareados por sexo e idade. Somente se observou diferença estatística em relação aos níveis de PTH e cálcio iônico, com p < 0,004 e p < 0,03, respectivamente. Hiperparatireoidismo secundário foi encontrado em oito (22.8%) pacientes do GL e em nenhum do GC. No GL, não houve correlação entre litemia, tempo de uso e posologia do CL. Conclusão: Nossos dados demonstram que o lítio pode suscitar um desequilíbrio no eixo paratireoideano, caracterizado por níveis elevados de PTH. .

Metabolismo mineral en niños en diálisis peritoneal crónica / Mineral metabolism in patients on chronic peritoneal dialysis

Introduction: Children with chronic kidney disease (CKD) and receiving peritoneal dialysis (PD) have disorders of mineral metabolism that impact their growth, survival and cardiovascular functions. New molecular markers offer a better understanding of the pathophysiology of this disease. Objective: To characterize some components of mineral metabolism, with emphasis on FGF23/Klotho and cardiovascular functions (CV) of these patients. Patients and Method: Prospective observational cohort study. Exclusion criteria: serum 25 (OH) vitamin D < 20 ng/ml, peritonitis within the last two months and active nephrotic syndrome. Calcemia, phosphemia, parathyroid hormone (PTH), 25 (OH) vitD3, 1.25 (OH) vitD3, FGF23 and Klotho in plasma were measured. FGF23 and Klotho were quantified in healthy children as a control group. Echocardiography was performed calculating the left ventricular mass index (LVMI). Descriptive statistics analysis, Pearson correlation coefficient for association among variables and multivariate analysis were conducted. Results: 33 patients, 16 males, aged between 1.2 and 13.4 years were included. Age of onset for PD: 7.3 +/- 5.0 years, time receiving PD: 13.5 +/- 14.5 months. The plasma concentration of 25 (OH) vitD3 was 34.2 +/- 6.3 pg/ml. Calcemia and phosphemia values were 9.8 ± 0.71 and 5.4 +/- 1.0 mg/dl respectively. PTH was 333 +/- 287 pg/ml. FGF23 in plasma was 225.7 +/- 354.3 pg/ml and Klotho 131.6 +/- 72 pg/ml, and in the controls ( n = 16 ), it was 11.9 +/- 7.2 pg/ml and 320 +/- 119 pg/ml, respectively. The residual and total dose of dialysis (KtV) was 1.6 +/- 1.3 and 2.9 +/- 1.6, respectively. FGF23 levels significantly correlated with calcium (p < 0.001, r = 0.85), and inversely with residual KtV, showing no relationship with phosphemia. Klotho level correlated negatively with residual KtV and also, it showed a negative association with chronological age and age at onset of PD. LVMI > 38 g/m² was confirmed in 20/28 patients...

Introducción: Los niños portadores de Enfermedad renal crónica (ERC) en diálisis peritoneal (DP) presentan alteraciones del metabolismo mineral que afectan su crecimiento, estado cardiovascular y sobrevida. Nuevos marcadores moleculares representan una mejor comprensión de la fisiopatología de esta enfermedad. Objetivo: Caracterizar componentes del metabolismo mineral, con énfasis en FGF23/Klotho, y estado cardiovascular (CV) en este grupo de pacientes. Pacientes y Método: Estudio prospectivo observacional. Criterios de exclusión: niveles de 25 (OH) vitamina D < 20 ng/ml, peritonitis hasta 2 meses previos y síndrome nefrótico activo. Se midió calcemia, fosfemia, paratohormona (PTH), 25 (OH) vitD3, 1,25 (OH) vitD3, FGF23 y Klotho en plasma. Se cuantificó FGF23 y Klotho en niños sanos como grupo control. Se efectuó ecocardiografía, calculándose el índice de masa ventricular izquierda (IMVI). Se realizó análisis estadístico descriptivo, coeficiente de correlación de Pearson para asociación entre variables y análisis multivariado. Resultados: Se incluyeron 33 pacientes, 16 varones, edad 1,2 a 13,4 años. Edad de inicio de DP: 7,3 +/- 5,0 años, tiempo en DP: 13,5 +/- 14,5 meses. El nivel plasmático de 25 (OH) vitD3 fue 34,2 +/- 6,3 pg/ml. Los valores de calcemia y fosfemia fueron 9,8 +/- 0,71 y 5,4 +/- 1,0 mg/dl respectivamente. La PTH fue de 333 +/- 287 pg/ml. El FGF23 en plasma fue de 225,7 +/- 354,3 pg/ml y Klotho 131,6 +/- 72 pg/ml, y en los controles (n = 16) fue de 11,9 +/- 7,2 pg/ ml y 320 +/- 119 pg/ml, respectivamente. La dosis de diálisis (KtV) residual y total fue de 1,6 +/- 1,3 y 2,9 +/- 1.6, respectivamente. El nivel de FGF23 se correlacionó significativamente con la calcemia (p < 0,001, r = 0,85), e inversamente con el KtV residual, sin mostrar relación con la fosfemia. El nivel de Klotho...