Fibroblast growth factor 23 (FGF23) exerts its effect by binding to its cognate FGF receptor 1 (FGFR1) in the presence of its co-receptor Klotho. Parathyroid glands express both FGFR1 and Klotho, and FGF23 decreases parathyroid hormone gene expression and hormone secretion directly. In uremic patients with secondary hyperparathyroidism (SHPT), however, parathyroid hormone secretion remains elevated despite extremely high FGF23 levels. To determine the mechanism of this resistance, we measured the expression of Klotho, FGFR1, and the proliferative marker Ki67 in 7 normal and 80 hyperplastic parathyroid glands from uremic patients by immunohistochemistry. All uremic patients had severe SHPT along with markedly high FGF23 levels. Quantitative real-time reverse transcription PCR showed that the mRNA levels for Klotho and FGFR1correlated significantly with their semi-quantitative immunohistochemical intensity. Compared with normal tissue, the immunohistochemical expression of Klotho and FGFR1 decreased, but Ki67 expression increased significantly in hyperplastic parathyroid glands, particularly in glands with nodular hyperplasia. These results suggest that the depressed expression of the Klotho-FGFR1 complex in hyperplastic glands underlies the pathogenesis of SHPT and its resistance to extremely high FGF23 levels in uremic patients.
Background and objectives: Cinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not been proven whether parathyroid gland size predicts response to therapy and whether cinacalcet is capable of inducing a reduction in parathyroid volume.Design, setting, participants, & measurements: This 52-week, multicenter, open-label study enrolled hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted between 25 and 100 mg to achieve intact PTH <180 pg/ml. Ultrasonography was performed to measure the parathyroid gland size at baseline, week 26, and week 52. Findings were also compared with those of historical controls.Results: Of the 81 subjects enrolled, 56 had parathyroid glands smaller than 500 mm 3 (group S) and 25 had at least one enlarged gland larger than 500 mm 3 (group L). Treatment with cinacalcet effectively decreased intact PTH by 55% from baseline in group S and by 58% in group L. A slightly greater proportion of patients in group S versus group L achieved an intact PTH <180 pg/ml (46 versus 32%) and a >30% reduction from baseline (88 versus 78%), but this was not statistically significant. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size, which was in sharp contrast to historical controls (n ؍ 87) where parathyroid gland volume progressively increased with traditional therapy alone.Conclusions: Cinacalcet effectively decreases serum PTH levels and concomitantly reduces parathyroid gland volume, even in patients with marked parathyroid hyperplasia.
SummaryBackground and objectives Lanthanum carbonate (LC) is a nonaluminum, noncalcium phosphate binder that is effective for hyperphosphatemia in dialysis patients. However, its efficacy and cost-effectiveness as second-line therapy have not been fully examined.
This study was conducted to examine whether oral-health promotion programs provided as an occupational health service for employees were cost-beneficial for employers. The subjects were composed of 357 male workers (20-59 yr of age) who participated in oral-health promotion programs conducted at their workplaces between 1992 and 1997. The design of this study was a quasi-experimental study design in which the three programs (light: 1 visit; medium: 2-4 visits; and heavy: 5-6 visits) were compared through cost-benefit analysis conducted from the viewpoint of the employers. The programs consisted of oral-health checkups by dentists and oral-health education, including that on the proper brushing method, by dental hygienists. The costs of the program included direct costs for the payment of oral-health-care staff and for teaching materials, and indirect costs for the time for employee participation in the program (20 min/employee per visit). The accumulated dental expenses for the seven years were used to calculate benefits, which were determined, based on the differences between 0 visits and each program. The benefit/cost ratios of the three programs were -2.45, 1.46, and 0.73, respectively. These results suggest that a worksite oral-health promotion program of medium frequency is cost-beneficial for employers.
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