Manejo de la osteoporosis en el paciente con enfermedad renal crónica (Estudio ERCOS): un desafío en la asistencia nefrológica / Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care

La valoración del riesgo de fractura del paciente con enfermedad renal crónica (ERC) ha sido incluida en el complejo Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) en guías nefrológicas internacionales y nacionales, sugiriéndose por primera vez la evaluación de la densidad mineral ósea (DMO) si los resultados pueden condicionar la toma de decisiones terapéuticas. Sin embargo, existe muy poca información en práctica clínica real en esta población. El objetivo principal del estudio ERC-Osteoporosis (ERCOS) es describir el perfil de los pacientes con ERC G3-5D con osteoporosis (OP) y/o fracturas por fragilidad atendidos en consultas especializadas de nefrología, reumatología y medicina interna en España. Participaron 15 centros y se incluyeron 162 pacientes (siendo en su mayoría mujeres [71,2%] posmenopáusicas [98,3%]) con una mediana de edad de 77 años. La mediana del filtrado glomerular estimado (FGe) fue de 36ml/min/1,73m2 y el 38% de pacientes incluidos estaban en diálisis. Destacamos la elevada frecuencia de fracturas por fragilidad prevalentes ([37,7%), principalmente vertebrales [52,5%] y de cadera 24,6%]), el antecedente desproporcionado de pacientes con enfermedad glomerular en comparación con series puramente nefrológicas (corticoides) y el infratratamiento para la prevención de fracturas, fundamentalmente en consultas nefrológicas. Este estudio supone una inmediata llamada a la acción con la difusión de las nuevas guías clínicas, más proactivas, y subraya la necesidad de homogeneizar el enfoque asistencial/terapéutico multidisciplinar coordinado de estos pacientes de un modo eficiente para evitar las actuales discrepancias y el nihilismo terapéutico. (AU)

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results will impact treatment decisions. However, there is very little information on actual clinical practice in this population. The main objective of the ERC-Osteoporosis (ERCOS) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36ml/min/1.73m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures ([37.7%], mainly vertebral [52.5%] and hip [24.6%]), the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and efficient multidisciplinary care/therapeutic approach to these patients to avoid current discrepancies and therapeutic nihilism. (AU)

Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism.

Impacto de la función renal en el valor pronóstico del metabolismo mineral en pacientes con cardiopatía isquémica crónica / Impact of renal function on the prognostic value of mineral metabolism in patients with chronic ischaemic heart disease patients with chronic ischaemic heart disease

INTRODUCCION: La parathormona (PTH) es un componente del metabolismo mineral (MM) que ha demostrado aportar valor pronóstico en los pacientes con cardiopatía isquémica crónica (CIC) y función renal preservada. Sin embargo, la influencia de la función renal en el papel pronóstico de la PTH en los pacientes con CIC aún no se ha demostrado.ObjetivoEvaluar la influencia del filtrado glomerular renal estimado (FGRe) sobre el papel pronóstico de la PTH y otros marcadores del MM en los pacientes con CIC. MÉTODOS: Analizamos el valor pronóstico de distintos componentes del MM (PTH, klotho, fósforo, calcidiol y factor de crecimiento de fibroblastos-23 [FGF23]) en 964 pacientes con CIC incluidos en 5 hospitales de Madrid en función de si presentaban FGRe <60ml/min/1,73m2 (LFGR) o FGRe≥60ml/min/1,73m2 (HFGR). El objetivo primario fue la combinación de muerte con eventos isquémicos (cualquier síndrome coronario agudo, accidente cerebrovascular isquémico o accidente isquémico transitorio). El FGR se calculó mediante el método Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTADOS: La edad era de 60,0 (52,0-72,0) años y el 76,2% de los casos eran varones, con una mediana del FGRe de 80,4 (65,3-93,1)ml/min/1,73m2. El seguimiento fue de 5,39 (2,81-6,92) años. Setecientos noventa pacientes presentaron HGFR y 174 LGFR. En pacientes con HFGR, los predictores del endpoint combinado fueron los niveles plasmáticos de calcidiol (HR=0,023 [0,94-0,99], p=0,023); FGF23 (HR=1,00 [1,00-1,003], p=0,036); colesterol no-HDL (HR=1,01 [1,00-1,01], p=0,026) y troponina de alta sensibilidad (HR=5,12 [1,67-15,59], p=0,004), junto con la edad (HR=1,03 [1,01-1,05], p=0,01), el tratamiento con estatinas (HR=0,36 [0,19-0,68], p=0,002); nitratos (HR=1,13 [1,07-2,79], p=0,027); dihidropiridinas (HR=1,71 [1,05-2,77], p=0,032); verapamilo (HR=5,71 [1,35-24,1], p=0,018) e inhibidores de la bomba de protones (HR=2,23 [1,36-3,68], p=0,002). [...]

BACKGROUND: Parathormone (PTH) is a component of the Mineral Metabolism (MM) system that has been shown recently to add prognostic value in pts. with stable coronary artery disease (SCAD) and average renal function. However, the influence of renal function on the prognostic role of PTH in pts. with SCAD has not been shown yet.PurposeTo assess the influence of estimated glomerular filtration rate (eGFR) on the prognostic role of PTH and other MM markers in pts. with SCAD. METHODS: We analyzed the prognostic value of MM markers (PTH, klotho, phosphate, calcidiol [25-hydroxyvitamin D], and fibroblast growth factor-23 [FGF23]) in 964 pts. with SCAD and eGFR<60ml/min/1.73 m2 (LGFR) vs pts. with eGFR≥60ml/min/1.73 m2 (HGFR) included in five hospitals of Madrid. The main outcome was the combination of death with ischemic events (any acute coronary syndrome, ischemic stroke or transient ischemic attack). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTS: Age was 60.0 (52.0-72.0) years, 76.2% of patients were men, and eGFR was 80.4 (65.3-93.1) ml/min/1,73 m2. Median follow-up was 5.39 (2.81-6.92) years. There were 790 pts. with HGFR and 174 with LGFR. In HGFR pts., predictors of ischemic events or death were plasma levels of calcidiol [HR=0.023 (0.94-0.99) p=0.023], FGF23 [HR=1.00 (1.00-1.003) p=0.036], non-HDL cholesterol [HR=1.01 (1.00-1.01) p=0.026] and high sensitivity troponin I [HR=5.12 (1.67-15.59) p=0.004], along with age [HR=1.03 (1.01-1.05) p=0.01], treatment with statins [HR=0.36 (0.19-0.68) p=0.002], nitrates [HR=1.13 (1.07-2.79) p=0.027], dihydropyridines [HR=1.71 (1.05-2.77) p=0.032], verapamil [HR=5.71 (1.35-24.1) p=0.018], and proton-pump inhibitors [HR=2.23 (1.36-3.68) p= 0.002]. [...]

Impact of renal function on the prognostic value of mineral metabolism in patients with chronic ischaemic heart disease patients with chronic ischaemic heart disease. / Impacto de la función renal en el valor pronóstico del metabolismo mineral en pacientes con cardiopatía isquémica crónica.

BACKGROUND: Parathormone (PTH) is a component of the Mineral Metabolism (MM) system that has been shown recently to add prognostic value in pts. with stable coronary artery disease (SCAD) and average renal function. However, the influence of renal function on the prognostic role of PTH in pts. with SCAD has not been shown yet. PURPOSE: To assess the influence of estimated glomerular filtration rate (eGFR) on the prognostic role of PTH and other MM markers in pts. with SCAD. METHODS: We analyzed the prognostic value of MM markers (PTH, klotho, phosphate, calcidiol [25-hydroxyvitamin D], and fibroblast growth factor-23 [FGF23]) in 964 pts. with SCAD and eGFR<60ml/min/1.73 m2 (LGFR) vs pts. with eGFR≥60ml/min/1.73 m2 (HGFR) included in five hospitals of Madrid. The main outcome was the combination of death with ischemic events (any acute coronary syndrome, ischemic stroke or transient ischemic attack). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTS: Age was 60.0 (52.0-72.0) years, 76.2% of patients were men, and eGFR was 80.4 (65.3-93.1) ml/min/1,73 m2. Median follow-up was 5.39 (2.81-6.92) years. There were 790 pts. with HGFR and 174 with LGFR. In HGFR pts., predictors of ischemic events or death were plasma levels of calcidiol [HR=0.023 (0.94-0.99) p=0.023], FGF23 [HR=1.00 (1.00-1.003) p=0.036], non-HDL cholesterol [HR=1.01 (1.00-1.01) p=0.026] and high sensitivity troponin I [HR=5.12 (1.67-15.59) p=0.004], along with age [HR=1.03 (1.01-1.05) p=0.01], treatment with statins [HR=0.36 (0.19-0.68) p=0.002], nitrates [HR=1.13 (1.07-2.79) p=0.027], dihydropyridines [HR=1.71 (1.05-2.77) p=0.032], verapamil [HR=5.71 (1.35-24.1) p=0.018], and proton-pump inhibitors [HR=2.23 (1.36-3.68) p= 0.002]. In the LGFR subgroup, predictors of death or ischemic events were PTH plasma levels, [HR=1.01 (1.00-1.01) p=0.005], eGFR [HR=0.96 (0.94-0.99) p=0.004], age [HR=1.06 (1.02-1.10) p=0.003], caucasian race [HR=0.04 (0.004-0.380) p=0.005], and treatment with insulin [HR=2.6 (1.20-5.63) p=0.015]. CONCLUSIONS: In pts. with SCAD, PTH is an independent predictor of poor outcomes only in those with eGFR<60ml/min/1.73 m2, while in pts. with eGFR≥60ml/min/1.73 m2 calcidiol and FGF23 become the only components of MM that may predict prognosis. Then, renal function influences the predictive power of MM markers in pts. with SCAD.

Hiporrespuesta o resistencia a la acción de la hormona paratiroidea en la enfermedad renal crónica / Hyporesponsiveness or resistance to the action of parathyroid hormone in chronic kidney disease

El hiperparatiroidismo secundario es uno de los componentes integrales de las alteraciones del metabolismo óseo-mineral en la enfermedad renal crónica (ERC) o complejo chronic kidney disease-mineral bone disorder. Se ha demostrado que en el desarrollo y progresión del hiperparatiroidismo secundario intervienen muchos factores, estrechamente interrelacionados, pero la presencia e importancia de la hiporrespuesta (o resistencia) a la acción de la hormona paratiroidea (PTH) es poco comprendida. En esta revisión analizaremos sus antecedentes, factores que intervienen, así como alguno de los mecanismos moleculares que podrían explicarla. La presencia de resistencia a la acción biológica de la PTH no es única en la ERC, ya que también se presenta para otras hormonas, habiéndose incluso usado el término de «uremia como una enfermedad de receptores». Esta hiporrespuesta a la PTH tiene importantes implicaciones clínicas, dado que no solo permite explicar parte de la patogenia progresiva de la hipersecreción de PTH e hiperplasia paratiroidea, sino también la creciente prevalencia de enfermedad ósea adinámica en la población con ERC. De este modo, subrayamos la importancia de controlar, sin normalizar completamente, los niveles de PTH en los distintos estadios de ERC, dado que un cierto incremento de sus niveles supone inicialmente una adaptación clínica. Futuros estudios a nivel molecular sobre la uremia, o la reciente descripción del efecto directo del fosfato sobre la actividad del receptor sensor de calcio como sensor de fosfato, podrían resultar valiosos incluso más allá de explicar la hiporrespuesta a la PTH en la ERC. (AU)

Secondary hyperparathyroidism (SHPT) is an integral component of the chronic kidney disease–mineral and bone disorder (CKD–MBD). Many factors have been associated with the development and progression of SHPT but the presence of skeletal or calcemic resistance to the action of PTH in CKD has often gone unnoticed. The term hyporesponsiveness to PTH is currently preferred and, in this chapter, we will not only review the scientific timeline but also some of the molecular mechanisms behind. Moreover, the presence of resistance to the biological action of PTH is not unique in CKD since resistance to other hormones has also been described (“uremia as a receptor disease”). This hyporesponsiveness carries out important clinical implications since it explains, at least partially, not only the progressive nature of the pathogenesis of CKD-related PTH hypersecretion and parathyroid hyperplasia but also the increasing prevalence of adynamic bone disease in the CKD population. Therefore, we underline the importance of PTH control in all CKD stages, but not aiming to completely normalize PTH levels since a certain degree of SHPT may represent an adaptive clinical response. Future studies at the molecular level, i.e. on uremia, or the recent description of the calcium-sensing receptor as a phosphate sensor, may become of great value beyond their significance to explain just the hyporesponsiveness to PTH in CKD. (AU)

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.

Composición corporal, metabolismo mineral y función endocrina del tejido adiposo: influencia de un suplemento nutricional de propóleo / Body composition, mineral metabolism, and endocrine function of adipose tissue: influence of a nutritional supplement of propolis

Introducción: el propóleo y sus componentes influyen en el metabolismo lipídico; sin embargo, se desconoce su efecto sobre la composición corporal y el metabolismo mineral. Objetivos: determinar el efecto de la suplementación de la dieta con propóleo natural sobre la composición corporal, el metabolismo basal y mineral, y la función endocrina del tejido adiposo. Material y métodos: veinte ratas albinas Wistar macho (8 semanas) se dividieron en dos grupos de 10 animales cada uno. Las ratas fueron alimentadas con dos tipos diferentes de dietas durante 90 días: una dieta estándar para el grupo de control (grupo C) y la misma dieta estándar + un 2 % de propóleo (grupo P). Se determinaron las hormonas tiroideas, la grelina, la leptina, la adiponectina y la insulina, los ácidos grasos no esterificados (AGNE) en el plasma, la composición corporal (masa magra, masa grasa y agua corporal) y el depósito de minerales en órganos diana (bazo, cerebro, corazón, pulmones, testículos, riñones y fémur). Resultados: los niveles plasmáticos de hormona estimulante del tiroides (TSH), triyodotironina (T3) y tiroxina (T4) no mostraron diferencias tras la ingesta del suplemento de propóleo, mientras que los de grelina y adiponectina disminuyeron (p < 0,01 y p < 0,05, respectivamente) y los de insulina (p < 0,01), leptina (p < 0,05) y AGNE (p < 0,05) aumentaron cuando la dieta se suplementó con propóleo al 2 %. Se redujeron el peso y la grasa corporal (p < 0,05), incrementándose la masa magra. Por último, el suplemento de propóleo mejoró el depósito de calcio en el bazo, los pulmones, los testículos y el fémur (p < 0,05). (AU)

Introduction: propolis and its components influence lipid metabolism; however, its effect on body composition and mineral metabolism remains unknown. Objectives: to determine the effect of natural propolis supplementation on body composition, mineral metabolism, and the endocrine function of adipose tissue. Material and methods: twenty albino male Wistar rats (8 weeks old) were divided into two groups of 10 animals each. The rats were fed two different types of diet for 90 days: a standard diet for the control group (group C) and the same standard diet + 2 % propolis (group P). Thyroid hormones, ghrelin, leptin, adiponectin and insulin, non-esterified fatty acids (NEFA) in plasma, body composition (lean mass, fat mass and body water), and mineral deposition in target organs (spleen, brain, heart, lungs, testicles, kidneys and femur) were assessed. Results: thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) did not show any differences after supplementation with propolis, while ghrelin and adiponectin decreased (p < 0.01 and p < 0.05, respectively) and insulin (p < 0.01), leptin (p < 0.05) and NEFA (p < 0.05) increased when 2 % propolis was supplied, while weight and body fat were reduced (p < 0.05) and lean mass increased. Lastly, the propolis supplement improves calcium deposition in the spleen, lungs, testes, and femur (p < 0.05). (AU)

[Body composition, mineral metabolism, and endocrine function of adipose tissue: influence of a nutritional supplement of propolis]. / Composición corporal, metabolismo mineral y función endocrina del tejido adiposo: influencia de un suplemento nutricional de propóleo.

INTRODUCTION: Introduction: propolis and its components influence lipid metabolism; however, its effect on body composition and mineral metabolism remains unknown. Objectives: to determine the effect of natural propolis supplementation on body composition, mineral metabolism, and the endocrine function of adipose tissue. Material and methods: twenty albino male Wistar rats (8 weeks old) were divided into two groups of 10 animals each. The rats were fed two different types of diet for 90 days: a standard diet for the control group (group C) and the same standard diet + 2 % propolis (group P). Thyroid hormones, ghrelin, leptin, adiponectin and insulin, non-esterified fatty acids (NEFA) in plasma, body composition (lean mass, fat mass and body water), and mineral deposition in target organs (spleen, brain, heart, lungs, testicles, kidneys and femur) were assessed. Results: thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) did not show any differences after supplementation with propolis, while ghrelin and adiponectin decreased (p < 0.01 and p < 0.05, respectively) and insulin (p < 0.01), leptin (p < 0.05) and NEFA (p < 0.05) increased when 2 % propolis was supplied, while weight and body fat were reduced (p < 0.05) and lean mass increased. Lastly, the propolis supplement improves calcium deposition in the spleen, lungs, testes, and femur (p < 0.05). Conclusion: propolis supplementation of the diet (2 %) causes a decrease in the secretion of ghrelin and adiponectin, increasing the release of non-esterified fatty acids and the rate of insulin secretion. In addition, propolis supplementation induces an improvement in calcium deposition in target organs without affecting the rest of minerals, which improves body composition by inducing a reduction in weight and visceral adipose tissue, and improvement in lean mass.

INTRODUCCIÓN: Introducción: el propóleo y sus componentes influyen en el metabolismo lipídico; sin embargo, se desconoce su efecto sobre la composición corporal y el metabolismo mineral. Objetivos: determinar el efecto de la suplementación de la dieta con propóleo natural sobre la composición corporal, el metabolismo basal y mineral, y la función endocrina del tejido adiposo. Material y métodos: veinte ratas albinas Wistar macho (8 semanas) se dividieron en dos grupos de 10 animales cada uno. Las ratas fueron alimentadas con dos tipos diferentes de dietas durante 90 días: una dieta estándar para el grupo de control (grupo C) y la misma dieta estándar + un 2 % de propóleo (grupo P). Se determinaron las hormonas tiroideas, la grelina, la leptina, la adiponectina y la insulina, los ácidos grasos no esterificados (AGNE) en el plasma, la composición corporal (masa magra, masa grasa y agua corporal) y el depósito de minerales en órganos diana (bazo, cerebro, corazón, pulmones, testículos, riñones y fémur). Resultados: los niveles plasmáticos de hormona estimulante del tiroides (TSH), triyodotironina (T3) y tiroxina (T4) no mostraron diferencias tras la ingesta del suplemento de propóleo, mientras que los de grelina y adiponectina disminuyeron (p < 0,01 y p < 0,05, respectivamente) y los de insulina (p < 0,01), leptina (p < 0,05) y AGNE (p < 0,05) aumentaron cuando la dieta se suplementó con propóleo al 2 %. Se redujeron el peso y la grasa corporal (p < 0,05), incrementándose la masa magra. Por último, el suplemento de propóleo mejoró el depósito de calcio en el bazo, los pulmones, los testículos y el fémur (p < 0,05). Conclusión: el suplemento de propóleo al 2 % de la dieta produjo una disminución de la secreción de grelina y adiponectina, incrementando la concentración de AGNE y aumentando la tasa de secreción de insulina. Además, el suplemento de propóleo indujo una mejora del depósito de calcio en los órganos diana sin afectar al resto de minerales, lo que en conjunto mejora la composición corporal al inducir una reducción del peso y del tejido adiposo visceral, mejorando la masa magra.

Hyporesponsiveness or resistance to the action of parathyroid hormone in chronic kidney disease.

Secondary hyperparathyroidism (SHPT) is an integral component of the chronic kidney disease-mineral and bone disorder (CKD-MBD). Many factors have been associated with the development and progression of SHPT but the presence of skeletal or calcemic resistance to the action of PTH in CKD has often gone unnoticed. The term hyporesponsiveness to PTH is currently preferred and, in this chapter, we will not only review the scientific timeline but also some of the molecular mechanisms behind. Moreover, the presence of resistance to the biological action of PTH is not unique in CKD since resistance to other hormones has also been described ("uremia as a receptor disease"). This hyporesponsiveness carries out important clinical implications since it explains, at least partially, not only the progressive nature of the pathogenesis of CKD-related PTH hypersecretion and parathyroid hyperplasia but also the increasing prevalence of adynamic bone disease in the CKD population. Therefore, we underline the importance of PTH control in all CKD stages, but not aiming to completely normalize PTH levels since a certain degree of SHPT may represent an adaptive clinical response. Future studies at the molecular level, i.e. on uremia or the recent description of the calcium-sensing receptor as a phosphate sensor, may become of great value beyond their significance to explain just the hyporesponsiveness to PTH in CKD.

Detection of cardiovascular calcifications: Is it a useful tool for nephrologists? / Detección de las calcificaciones cardiovasculares: ¿una herramienta útil para el nefrólogo?

Chronic kidney disease (CKD) has been used as a model and source of knowledge concerning the mechanisms, clinical relevance and accelerated progression of cardiovascular (CV) calcification, as well as its consequences in clinical practice, despite we know that it is a late secondary ossification phenomenon and only circumstantial evidence is available. In this comprehensive review, we firstly describe the types of CV calcification which affect CKD patients, and we analyse how its presence is directly associated with CV events and increased mortality in these patients. We also justify the use of CV calcification assessment in regular nephrology clinical practice, because CV calcification is an important predictor of clinical outcome in these patients. Consequently, we believe that CV calcification assessment is a tool that could and should be used by nephrologists when making a decision concerning individual patients, consistent with the current trend of an ever-more-personalised therapeutic approach.

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.

Hipomagnesemia subclínica em vacas leiteiras durante o período de transição: ocorrências hormonais e metabólicas

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.

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.

Vitamina D: una hormona poderosa: [Editorial] / Vitamin D: a powerful hormone: [Editorial]

La vitamina D representa uno de los principales factores determinantes para el desarrollo de la vida en la tierra y para la evolución humana. Aproximadamente el 10% al 20% de los requerimiento de vitamina D de un organismo humano se puede obtener a través de la dieta y aproximadamente el 90% del total de la vitamina D necesaria tiene que ser fotosintetizada en la piel a través de la acción del sol (luz ultravioleta B (UV-B)) [1].El raquitismo por deficiencia de vitamina D fue la enfermedad de los jóvenes entre 1800 y principiosdel siglo XX, con proporciones epidémicas en el norte de Europa, Norteamérica y Asia del Norte [2]. Sir Edward Mellanby (1919) demostró que esta enfermedad era debida a una deficiencia nutricional y se podía mejorar con suplementos de aceite de hígado de bacalao. McCollum (1922) demostró que el factor terapéutico en este aceite era una nueva vitamina, la vitamina D [3,4]. Por su parte, Huldshinsky y sus compañeros de trabajo (1919) también demostraron que el raquitismo podía ser tratado con la luz ultravioleta (UV). Así mismo, Steenbock (1923) demostró que la luz UV inducía la formación de vitamina D en las porciones grasas de los alimentos y en la piel, y mediante la irradiación de alimentos, logró proporcionar los medios por los cuales el raquitismo podría dejar de ser un problema médico importante...

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...

Avaliação do metabolismo mineral do doador de rim em vida / Evaluation of mineral metabolism in living kidney donor

Introdução: Doador de rim em vida é uma importante fonte de órgão para os pacientes portadores de doença renal crônica (DRC). Os doadores experimentam uma redução abrupta da taxa de filtração glomerular (TFG) e adaptações ao metabolismo mineral demandam estudos nesta população. Nós avaliamos prospectivamente esta adaptação em doadores de rim em vida. Métodos: Entre janeiro de 2010 a agosto de 2011, no hospital das Clínicas de São Paulo e na Universidade de Miami, realizamos a avaliação prospectiva do metabolismo mineral e da função renal por 1 ano em 74 doadores de rim em vida. Medimos a taxa de filtração glomerular (TFG), fósforo (Pi), cálcio (Ca), paratohormônio (PTH), fibroblast Growth Factor 23 (FGF23) e a fração de excreção do fósforo (FePO4) no pré-operatório e nos dias 1, 2, 14, 180 e 360 do pós-operatório. Resultados: Observamos uma redução, aproximadamente, de 40% da TFG nos dois primeiros dias após a cirurgia. No décimo quarto dia após a nefrectomia, observamos o início da recuperação da TFG, chegando ao máximo da recuperação com 1 ano, quando se atingiu 68,6% da função renal se comparado com o dia anterior a doação (75,3 ml/min/1,73m2, p < 0,001). O cálcio sérico apresentou seu nadir no dia 1 (7,99 mg/dL; p < 0,01) e o Pi sérico atingiu seu nadir no dia 2 (2,61 mg/dL; p < 0,01). Já no dia 14, os valores de Ca e Pi retornaram aos valores basais tendo o fósforo evoluído novamente com valores inferiores ao basal no último dia de seguimento (3,36mg/dL; p < 0,001). FGF23 e PTH apresentaram elevação no D1 (111,0144,6 percentil 25-75: 16-63 RU/ml 64,9 30,3pg/mL; p < 0,01). Os valores de FGF23 se mantiveram elevados até o final do estudo enquanto que o PTH retornou aos valores de base no segundo dia e, a partir de então, manteve sem diferença do valores basais até o último dia de estudo. FePO4 elevou de 11,45,2% para 15,28,1% entre o pré-operatório e D365 (p < 0,01). Conclusão: A nefrectomia para doação de rim em 74 pacientes saudáveis elevou os valores...

Introduction: Living kidney donors (LKDs) experience an abrupt decline in glomerular filtration rate (GFR). Mineral metabolism adaptations in early CKD are still debated and not well studied in LKDs. We prospectively studied acute and long term mineral metabolism adaptation of LKDs. Materials and Methods: We measured renal function and mineral metabolites longitudinally for 1 year (days (D) 1, 2, 14, 180, & 365 post-operatively) in 74 healthy individuals who underwent kidney live donation. Results: eGFR (MDRD) decreased to 59% of its baseline on day 2 and started to increase at day 3, to its maximum at day 360 (75.3±15.6 ml/min/1.73m2, p < 0.01) wile FGF23 increased from 60.6 (25th-75th percentile 19-81 RU/mL) at baseline to 111.0±144.6 (p < 0.01) on day 1 and keep higher than baseline throwout the study. PTH rose maximally on day 1 (64.9 ± 30.3pg/ml) and returned to its base line on D2 and did not change after that. Total serum Calcium levels decreased from 9,40±0,48 mg/dL to a nadir of 7.99±0,51 mg/dL on day 1 (p < 0.001). Serum Phosphate levels reached their nadir on day 2 (2.61±0,52 mg/dL; p < 0.01). At D14 total calcium and phosphate levels had returned to baseline, but phosphate levels returned down on D360 (3.36±0,52 mg/dL; p < 0.001). Phosphate excretion fraction (FePO4) increased from base line (11.4±5.2%) up to 15.2±8.1% until D360 (p < 0.001). Conclusions: Abrupt reduction in eGFR induces physiological increases in FGF23 and PTH, and decreases in serum Ca and Pi in the first week. The changes in FGF23 and Pi urinary fractional excretion of Pi remain modestly yet significantly different from baseline throughout the first year after nephrectomy. Wile Ca, PTH and Pi serum levels are not significantly different from the baseline...

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.

Avaliação da relação entre metabolismo mineral e doença arterial coronariana em pacientes com função renal preservada / Evaluation of the relationship between mineral metabolism and coronary artery disease in patients with preserved renal function

INTRODUÇÃO: Os níveis séricos de fósforo (P) têm sido associados a doenças cardiovasculares e mortalidade em pacientes com doença renal crônica e na população geral. Estudos in vitro demonstram que altas concentrações de fósforo extracellular são capazes de induzir calcificação vascular e disfunção endotelial. O Fibroblast Growth Factor 23 (FGF-23) é um hormônio fosfatúrico e foi relacionado à presença de aterosclerose em pacientes idosos. OBJETIVO: O objetivo deste estudo foi investigar as relações entre P, FGF-23 e outros atores do metabolismo mineral e a ocorrência de doença arterial coronariana em pacientes com função renal preservada. MÉTODOS: Duzentos e noventa pacientes clinicamente estáveis com indicação de cineangiocoronariografia eletiva e clearance de creatinina superior a 60 ml/min/1.73 m2 foram submetidos à Tomografia Computadorizada Multislice para avaliação da calcificação coronariana e coleta de sangue para dosagens bioquímicas. A calcificação coronariana foi quantificada através do Escore de Agatston (EA) e os Escores de Friesinger e Gensini foram calculados para quantificar a obstrução coronariana. RESULTADOS: A média de idade dos pacientes foi 58,1± 9,3 anos, 81% eram hipertensos e 35,5% diabéticos. Os pacientes foram divididos em grupos de acordo com o EA utilizando-se como ponto de corte o valor de 10 Unidades Hounsfield (HU). O P sérico foi maior no grupo de pacientes com EA > 10 HU (3,63 0,55 vs 3,49 0,52mg/dL; p=0,019). Cada 1 mg/dL de elevação no P sérico associou-se a um aumento de 92% no risco de apresentar o EA > 10HU [Odds Ratio (OR) =1,92, CI 1,56-3,19; p=0,01]. Quando os pacientes foram divididos de acordo com a mediana do Escore de Friesinger (4 pontos), o grupo com valores superiores à mediana apresentou P sérico maior (3,6 0,5 vs. 3,5 0,6 mg/dl; p=0,04) e FGF-23 menor (mediana 40,3 pg/mL intervalo interquartil 24,1-62,2 vs. 45,7 pg/mL intervalo interquartil 31,7-76,1; p=0,01) quando comparado àquele com valores...

INTRODUCTION: Serum phosphorus (P) has been associated with cardiovascular diseases and mortality in chronic kidney disease patients and in the general population. In vitro studies suggest that excessive phosphorus induces vascular calcification and endothelial dysfunction. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone and has been correlated to atherosclerosis in the community. AIM: This study intended to investigate the associations between P, FGF-23 and other mineral metabolism players and coronary artery disease in patients with preserved renal function. METHODS: Two-hundred ninety patients with a creatinine clearance higher than 60ml/min/1,73m2 undergoing elective coronary angiography were submitted to Multislice Computed Tomography in order to evaluate coronary calcification and blood was collected for biochemical analyses. Coronary artery calcification was quantified using the Agatston Score (AS). Friesinger (FS) and Gensini Scores (GS) were calcutalet to quantify coronary obstruction. RESULTS: Considering the whole population, mean age was 58.1±9.3 anos, 81% were hypertensive and 35.5% were diabetics. Patients were divided according to AS using the value of 10 Hounsfield Units (HU) as the cutoff.point. Serum phosphorus was higher in patients with an AS > 10HU when compared to the group with an AS 10 HU (3.63 0.55 vs 3.49 0.52mg/dL, p=0.019). Each 1 mg/dL of elevation in the serum phosphorus implied a 92% additional risk of presenting an AS > 10 HU [Odds Ratio (OR) =1.92, CI 1.56-3.19; p=0.01]. Patients were also divided using the median Friesinger score (4 points) as the cutoff value. Serum phosphorus was higher (3.6 0.5 vs. 3.5 0.6 mg/dl, p=0.04) and intact FGF-23 was lower (median 40.3 interquartile range 24.1-62.2 pg/mL vs. 45.7 interquartile range 31.7- 76.1 pg/mL, p=0.01) in the FS > 4 group. Patientis in the higher Gensini Score tertile presented elevated serum phosphorus when compared to the other groups (p<0,05). In the...