Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with ...normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia.
Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid ...hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats.
The interest on magnesium (Mg) has grown since clinical studies have shown the efficacy of Mg-containing phosphate binders. However, some concern has arisen for the potential effect of increased ...serum Mg on parathyroid hormone (PTH) secretion. Our objective was to evaluate the direct effect of Mg in the regulation of the parathyroid function; specifically, PTH secretion and the expression of parathyroid cell receptors: CaR, the vitamin D receptor (VDR) and FGFR1/Klotho.
The work was performed in vitro by incubating intact rat parathyroid glands in different calcium (Ca) and Mg concentrations.
Increasing Mg concentrations from 0.5 to 2 mM produced a left shift of PTH-Ca curves. With Mg 5 mM, the secretory response was practically abolished. Mg was able to reduce PTH only if parathyroid glands were exposed to moderately low Ca concentrations; with normal-high Ca concentrations, the effect of Mg on PTH inhibition was minor or absent. After 6-h incubation at a Ca concentration of 1.0 mM, the expression of parathyroid CaR, VDR, FGFR1 and Klotho (at mRNA and protein levels) was increased with a Mg concentration of 2.0 when compared with 0.5 mM.
Mg reduces PTH secretion mainly when a moderate low calcium concentration is present; Mg also modulates parathyroid glands function through upregulation of the key cellular receptors CaR, VDR and FGF23/Klotho system.
Background. Acanthosis nigricans (AN) is a clinical sign that commonly occurs in obesity; however, its specificity and sensitivity have been controversial. It is unknown if AN severity degree can be ...a useful marker for cardiometabolic disorders screening. We suggest that the stratified analysis of AN severity degree in neck by Burke’s scale could be a useful tool in the screening of cardiometabolic alterations in obese children. Objective. The aim of this study was the association of AN severity degree in neck by Burke’s scale with anthropometric, biochemical, and inflammatory parameters in obese school-age children from Mexico City. Methods. A cross-sectional study was conducted, including 95 obese school-age children stratified by AN severity degree in neck by Burke’s scale. Anthropometric and fasting biochemical measurements were determined. Variables were compared by x2 test for frequencies and one-way ANOVA with Bonferroni posttest for continuous variables. Linear regression analysis adjusted by gender, BMI, and age was performed to evaluate the association between AN severity degree and cardiometabolic alterations. Statistical significance was set at p<0.05. Results. As AN severity degree in neck by Burke’s scale increased, diastolic blood pressure (p=0.001) and triglycerides (p=0.02) significantly increased and adiponectin significantly decreased (p=0.02). Positive associations between grade 3 AN and waist circumference, HOMA-IR, triglycerides, total cholesterol, and LDL cholesterol were observed. Conclusion. Our findings could be used to identify an easier clinical tool to prevent obesity progression and its complications in pediatrics. There are no similar studies.
Although magnesium has been shown to prevent vascular calcification in vitro, controlled in vivo studies in uremic animal models are limited. To determine whether dietary magnesium supplementation ...protects against the development of vascular calcification, 5/6 nephrectomized Wistar rats were fed diets with different magnesium content increasing from 0.1 to 1.1%. In one study we analyzed bone specimens from rats fed 0.1%, 0.3%, and 0.6% magnesium diets, and in another study we evaluated the effect of intraperitoneal magnesium on vascular calcification in 5/6 nephrectomized rats. The effects of magnesium on established vascular calcification were also evaluated in uremic rats fed on diets with either normal (0.1%) or moderately increased magnesium (0.6%) content. The increase in dietary magnesium resulted in a marked reduction in vascular calcification, together with improved mineral metabolism and renal function. Moderately elevated dietary magnesium (0.3%), but not high dietary magnesium (0.6%), improved bone homeostasis as compared to basal dietary magnesium (0.1%). Results of our study also suggested that the protective effect of magnesium on vascular calcification was not limited to its action as an intestinal phosphate binder since magnesium administered intraperitoneally also decreased vascular calcification. Oral magnesium supplementation also reduced blood pressure in uremic rats, and in vitro medium magnesium decreased BMP-2 and p65–NF-κB in TNF-α–treated human umbilical vein endothelial cells. Finally, in uremic rats with established vascular calcification, increasing dietary magnesium from 0.1% magnesium to 0.6% reduced the mortality rate from 52% to 28%, which was associated with reduced vascular calcification. Thus, increasing dietary magnesium reduced both vascular calcification and mortality in uremic rats.
Background/Aims: Vascular calcification (VC), a major complication in humans and animals with chronic kidney disease (CKD), is influenced by changes in acid-base balance. The purpose of this study ...was to describe the acid-base balance in uremic rats with VC and to correlate the parameters that define acid-base equilibrium with VC. Methods: Twenty-two rats with CKD induced by 5/6 nephrectomy (5/6 Nx) and 10 nonuremic control rats were studied. Results: The 5/6 Nx rats showed extensive VC as evidenced by a high aortic calcium (9.2 ± 1.7 mg/g of tissue) and phosphorus (20.6 ± 4.9 mg/g of tissue) content. Uremic rats had an increased pH level (7.57 ± 0.03) as a consequence of both respiratory (PaCO2 = 28.4 ± 2.1 mm Hg) and, to a lesser degree, metabolic (base excess = 4.1 ± 1 mmol/l) derangements. A high positive correlation between both anion gap (AG) and strong ion difference (SID) with aortic calcium (AG: r = 0.604, p = 0.02; SID: r = 0.647, p = 0.01) and with aortic phosphorus (AG: r = 0.684, p = 0.007; SID: r = 0.785, p = 0.01) was detected. Conclusions: In an experimental model of uremic rats, VC showed high positive correlation with AG and SID.
This study describes fiber-type adaptations in hindlimb muscles, the interaction of sex, and the role of hypoxia on this response in 12-wk ⅚ nephrectomized rats (Nx). Contractile, metabolic, and ...morphological features of muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of Nx rats, and compared with sham-operated controls. Rats of both sexes were considered in both groups. A slow-to-fast fiber-type transformation occurred in the tibialis cranialis of Nx rats, particularly in males. This adaptation was accomplished by impaired oxidative capacity and capillarity, increased glycolytic capacity, and no changes in size and nuclear density of muscle fiber types. An oxidative-to-glycolytic metabolic transformation was also found in the soleus muscle of Nx rats. However, a modest fast-to-slow fiber-type transformation, fiber hypertrophy, and nuclear proliferation were observed in soleus muscle fibers of male, but not of female, Nx rats. Serum testosterone levels decreased by 50% in male but not in female Nx rats. Hypoxia-inducible factor-1α protein level decreased by 42% in the tibialis cranialis muscle of male Nx rats. These data demonstrate that 12 wk of Nx induces a muscle-specific adaptive response in which myofibers do not change (or enlarge minimally) in size and nuclear density, but acquire markedly different contractile and metabolic characteristics, which are accompanied by capillary rarefaction. Muscle function and sex play relevant roles in these adaptations.
RESUMEN Introducción: la comorbilidad es la presencia de enfermedades coexistentes o adicionales en relación al diagnóstico inicial o enfermedad guía. Es más frecuente en ancianos y contribuye a la ...aparición de eventos adversos de salud como mayor duración de la internación y mortalidad hospitalaria. Objetivo: determinar el efecto de las comorbilidades en la duración de la internación y en la mortalidad intrahospitalaria de los pacientes ingresados en el Servicio de Clínica Médica del Hospital Nacional (Itauguá, Paraguay) y del Hospital Militar Central (Asunción, Paraguay) entre marzo y julio del 2019. Materiales y métodos: se aplicó diseño de cohortes prospectivas en base al índice de comorbilidad de Charlson con punto de corte en 3 puntos. Ingresaron al estudio todos los varones y mujeres, mayores de 16 años, ingresados al Servicio de Clínica Médica del Hospital Nacional (Itauguá, Paraguay) y del Hospital Militar Central (Asunción, Paraguay) entre marzo y julio 2019. Se aplicó muestreo no probabilístico de casos consecutivos. Se midieron dos variables dependientes: duración de la hospitalización y mortalidad intrahospitalaria. Se calculó RR (IC 95%) y se consideró significativa toda p<0,05. El estudio respetó las normas éticas. Resultados: se incluyeron 543 sujetos, con predominio del sexo masculino (56%). La edad media fue 52±20 años. La mediana del índice de Charlson fue 2 puntos. No se detectó asociación estadísticamente significativa entre la severidad de este índice y la duración de la internación pero la mortalidad intrahospitalaria fue mayor con índice de Charlson ≥4: 6,5% vs 14,5% (p 0,005). Conclusiones: la mediana del índice de Charlson en dos Servicios de Clínica Médica fue 2. Se halló asociación estadísticamente significativa entre este índice y la mortalidad hospitalaria.
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