Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration ...decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH‐clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of β‐catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.
In vivo studies used 5/6 nephrectomy with parathyroidectomy and replacement of exogenous PTH to eliminate the osteogenic effect of PTH comparing the bone effects of calcitriol vs calcimimetic. The osteogenesis of mesenchymal stem cells in presence of calcitriol was also evaluated. Results show calcimimetic increases bone formation, while calcitriol reduces it. In vitro, calcitriol presence reduces mineralization and osteogenesis of stem cells into osteoblasts. In this experimental study and independently of PTH, we demonstrate that calcitriol administration reduces bone formation.
Cognitive impairment (CI) is a complication of chronic kidney disease (CKD) that is frequently observed among patients. The aim of this study was to evaluate the potential crosstalk between changes ...in cognitive function and the levels of Klotho in the brain cortex in an experimental model of CKD. To induce renal damage, Wistar rats received a diet containing 0.25% adenine for six weeks, while the control group was fed a standard diet. The animals underwent different tests for the assessment of cognitive function. At sacrifice, changes in the parameters of mineral metabolism and the expression of Klotho in the kidney and frontal cortex were evaluated. The animals with CKD exhibited impaired behavior in the cognitive tests in comparison with the rats with normal renal function. At sacrifice, CKD-associated mineral disorder was confirmed by the presence of the expected disturbances in the plasma phosphorus, PTH, and both intact and c-terminal FGF23, along with a reduced abundance of renal Klotho. Interestingly, a marked and significant decrease in Klotho was observed in the cerebral cortex of the animals with renal dysfunction. In sum, the loss in cerebral Klotho observed in experimental CKD may contribute to the cognitive dysfunction frequently observed among patients. Although further studies are required, Klotho might have a relevant role in the development of CKD-associated CI and represent a potential target in the management of this complication.
The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is ...associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3–4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC).
Patients with CKD stages 3–4 were randomized into controls (n=12) or intervention (n=7) group receiving 360mg of Mg carbonate daily during a 15-month period. Parameters related to mineral metabolism, BMD, VC, and pulse wave velocity (PWV) were evaluated.
Supplementation with Mg produced an increase in the urinary excretion of Mg while serum Mg levels remained stable and no episodes of hypermagnesemia were reported. In addition, no significant changes were found in the degree of VC assessed by Adragao index, however, both serum and urine Mg were significantly associated with a decrease in PWV, suggesting an increase in vascular compliance. Likewise, BMD did not change following treatment, but serum Mg significantly correlated with the levels of N-terminal propeptide of collagen alpha-1(I) chain (PINP), a marker of bone synthesis.
In sum, these results suggest a possible beneficial effect of Mg on vascular compliance with no detrimental effects on bone status. In addition, our results highlight the need to consider monitorization of urinary Mg status in CKD patients.
La progresión de la enfermedad renal crónica (ERC) supone el desarrollo de alteraciones del metabolismo mineral que están estrechamente relacionadas con eventos cardiovasculares y enfermedad ósea. La hipomagnesemia se asocia con una progresión más rápida de la ERC, así como con otras comorbilidades. Nuestro objetivo fue analizar en pacientes con ERC estadios 3-4 el impacto de la administración de carbonato de magnesio (Mg) sobre la densidad mineral ósea (DMO) y los cambios hemodinámicos asociados a la calcificación vascular (CV).
Los pacientes con enfermedad renal crónica estadios 3-4 se distribuyeron aleatoriamente en los grupos control (n=12) o intervención (n=7), que recibió 360 mg de carbonato de Mg diariamente durante un periodo de 15 meses. Se evaluaron parámetros relacionados con el metabolismo mineral además de la DMO, CV, y velocidad de onda de pulso (VOP).
La suplementación con Mg produjo un aumento en la excreción urinaria de Mg, mientras que los niveles séricos de Mg permanecieron estables y no se reportaron episodios de hipermagnesemia. Además, no se observaron cambios significativos en cuanto al grado de CV valorado en base al índice de Adragao. No obstante, tanto los niveles séricos como urinarios de Mg se asociaron significativamente con un descenso en la VOP, lo que sugiere un aumento en la distensibilidad vascular. De manera similar, la DMO no se modificó con la administración del tratamiento, pero los niveles séricos de Mg correlacionaron significativamente con los del propétido N-terminal del colágeno tipo I (PINP), un marcador de la síntesis ósea.
En conjunto, estos resultados sugieren un posible efecto beneficioso del Mg sobre la distensibilidad vascular sin efectos negativos a nivel óseo. Además, nuestros resultados subrayan la necesidad de considerar la monitorización del nivel de Mg urinario en pacientes con ERC.
