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Antecedentes: El efecto de cinacalcet en pacientes con hiperparatiroidismo secundario persistente (HPTS) tras el trasplante renal (TR) ha sido descrito principalmente en pacientes con hipercalcemia secundaria. Objetivos: Nuestro objetivo fue evaluar el efecto a largo plazo de cinacalcet en pacientes con TR y HPTS normocalcémico. Métodos: Estudio multicéntrico, observacional, retrospectivo, de un año, que incluyó receptores renales con HPTS (hormona paratiroidea intacta [PTHi] > 120 pg/ml) y niveles de calcio dentro de la normalidad (8,4-10,2 mg/dl) que iniciaron cinacalcet en la práctica clínica. Resultados: Se incluyeron 32 pacientes con una edad media (desviación estándar [DE]) de 54 (11) años, 56 % varones. El tratamiento con cinacalcet se inició una mediana de 16 meses después del TR (dosis mediana de 30 mg/día). Los niveles de PTHi disminuyeron desde una mediana (P25, P75) de 364 (220, 531) pg/ml al inicio del estudio a 187 (98, 320) a los 6 meses (reducción del 48,6 %, p = 0,001) y a 145 (91, 195) a los 12 meses (reducción del 60,2 %, p = 0,001), sin cambios en los niveles de calcio y fósforo (p = 0,214 y p = 0,216, respectivamente). No se observaron cambios en la función renal ni en los niveles de fármacos anticalcineurínicos. El 3,1 % de los pacientes interrumpió cinacalcet debido a intolerancia, y el 6,2 %, debido a falta de eficacia. Conclusiones: En pacientes con HPTS normocalcémico tras el TR, cinacalcet mejora el control de los valores séricos de PTH sin provocar cambios en la calcemia o fosfatemia ni en la función renal. Cinacalcet mostró una buena tolerabilidad (AU)

Background: The effect of cinacalcet in patients with persistent secondary hyperparathyroidism (SHPT) after kidney transplantation (RT) has mainly been reported in patients with secondary hypercalcaemia. Objectives: Our objective was to assess the long-term effect of cinacalcet on patients with a RT and normocalcaemic SHPT. Methods: A one-year multicentre, observational, retrospective study that included kidney recipients with SHPT (intact parathyroid hormone [iPTH] >120pg/ml) and calcium levels within the normal range (8.4-10.2mg/dl). Patients began treatment with cinacalcet in clinical practice. Results: 32 patients with a mean age (standard deviation [SD]) of 54 (11) years, 56% male, were included in the study. Treatment with cinacalcet began a median of 16 months after RT (median dose of 30mg/day). Levels of iPTH decreased from a median (P25, P75) of 364 (220, 531) pg/ml at the start of the study to 187 (98, 320) after 6 months (48.6% reduction, P=.001) and to 145 (91, 195) after 12 months (60.2% reduction, P=.001), without there being changes in calcium and phosphorus levels (P=.214 and P=.216, respectively). No changes were observed in kidney function or anti-calcineuric drug levels. 3.1% of patients discontinued cinacalcet due to intolerance and 6.2% due to a lack of efficacy. Conclusions: In patients with normocalcaemic SHPT after RT, cinacalcet improves the control of serum PTH values without causing changes to calcaemia, phosphataemia or kidney function. Cinacalcet showed good tolerability (AU)

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Dietary short-chain fructooligosaccharides (Sc-FOS) increase mucosal calbindin-D9k (CaBP) levels in the large intestine whereas levels in the small intestine are decreased in rats. In the present study, we investigated the mechanism by which Sc-FOS induce this increase in CaBP in the large intestine by measuring intestinal CaBP levels in rats fed normal and calcium-deficient diets. Dietary groups included a calcium-containing (0.5%) diet with or without Sc-FOS (100 g/kg diet) and a calcium-deficient (abt. 0.01%) diet with or without Sc-FOS (100 g/kg diet). The rats were fed these diets for 10 days following which they were killed and the intestine removed for collection of the entire mucosa which was divided into four segments, i.e., proximal and distal segments of the small intestine, the cecum and the colorectum. Mucosal CaBP and plasma calcium (Ca), 1,25-dihydroxycholecalciferol (1,25(OH)2D3), 25-hydroxycholecalciferol (25(OH)D3), parathyroid hormone (PTH) and calcitonin levels were measured. Feeding of calcium deficient diet resulted in an increase in CaBP levels in the small intestine, but did not influence levels in the large intestine. Moreover, a significant positive correlation between plasma 1,25(OH)2D3 and CaBP levels in the case of both small intestinal segments (proximal, r = 0.77012, p < 0.00007; distal, r = 0.75056, p < 0.00014) was observed, but not in the case of the large intestinal segments. Sc-FOS increased CaBP levels in the large intestine. These results suggest that the large intestinal CaBP levels do not change in response to dietary calcium conditions and are not regulated by circulating 1,25(OH)2D3 indicating that the effect of Sc-FOS on CaBP levels in the large intestine is independent of the action of 1,25(OH)2D3.

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The steroid hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] induces expression of the gene encoding calbindin-D28K, a protein involved in intestinal Ca2+ transport. Glucocorticoids stimulate intestinal development and function, and presumed interaction with 1,25-(OH)2D3 has been intensively studied. Most studies involved administration of high doses of glucocorticoids in vivo, which inhibits intestinal Ca2+ transport by an unknown mechanism. However, it is now known from studies of the duodenal organ culture model that low concentrations of glucocorticoids enhance 1,25-(OH)2D3-dependent calbindin-D28K biosynthesis and Ca2+ transport. High concentrations mimic the action of administered glucocorticoids in vivo, suggesting that a distinct pharmacological or toxic mechanism causes inhibition of Ca2+ absorption. This report further shows that dexamethasone (DEX) rapidly enhanced calbindin-D28K gene expression, that is de novo calbindin-D28K mRNA biosynthesis. DEX also markedly reduced the actions of RNA and protein synthesis inhibitors on calbindin-D28K gene expression, although no evidence for an action of DEX or 1,25-(OH)2D3 at the translational level was obtained. Ca2+ transport activity was highly correlated with calbindin-D28K concentration regardless of treatment. Washout permitted complete reversal of inhibition, verifying the specificity of inhibitor activity. These results appear to show positive contranscriptional regulation of calbindin-D28K gene expression by 1,25-(OH)2D3 and glucocorticoids. The use of this model should continue to clarify the interactive roles of nuclear-acting hormones on the Ca2+ absorptive mechanism and on complex physiological and pathological processes in general.

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The vitamin D-dependent calcium binding proteins (calbindins) are members of the troponin-C superfamily of proteins that occur in a number of calcium-transporting tissues such as the intestine, the distal tubule of the kidney, and the placenta. They are also present in other tissues such as the brain, peripheral nervous system, pancreas, parathyroid gland, and bone. In some tissues, such as the adult brain, the proteins occur in the absence of the vitamin. The proteins bind calcium in "EF" hand structures and are "calcium-sensitive" in that they undergo a conformational change on binding calcium. They appear to enhance transcellular calcium transport and are frequently present in tissues that contain the plasma membrane calcium pump.

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