These results suggest that lower dose levels of cinacalcet, as compared to those in US/EU studies, may be sufficient effectively suppress the serum iPTH levels and allow favourable management of the serum calcium and phosphorus levels in Japanese patients, having a longer average dialysis vintage.

107 hemodialysis patients at high risk for intradialytic bleeding due to previous surgery or active bleeding from other sites were treated with nafamostat mesilate (FUT-175; FUT) as hemodialysis anticoagulant for 2 weeks. In contrast to heparin. FUT prolonged clotting times only in the extracorporeal circuit. Clotting times were not prolonged even at the conclusion of the treatment, and bleeding from the puncture site after removal of the needle was shorter than with heparin. The exacerbation of bleeding by hemodialysis was noted in only 21 out of 573 hemodialysis procedures (3.7%), and 134 of 145 hemodialysis procedures (92.4%) with active bleeding were successfully completed without increasing the bleeding. Adverse effects of FUT were noted in only 6 cases (5.6%) or 1.2% of HD procedures. These results indicate that FUT is a very useful anticoagulant for HD, especially in patients with high risk of bleeding.

Abstract.The reduced expression level of the calcium-sensing receptor (CaR) is attributed to the hyposensitivity of parathyroid cells to extracellular calcium concentration [Ca 2ϩ ]o, which plays a crucial role in the pathogenesis of secondary hyperparathyroidism (SHPT) in patients and rats with chronic renal insufficiency (CRI). Calcimimetic compounds have been demonstrated to improve the decreased sensitivity of CaR to extracellular calcium concentration and to suppress both parathyroid hormone (PTH) oversecretion and parathyroid cell proliferation. However, the effect of calcimimetics on the reduced CaR expression level in parathyroid cells in CRI remains unclarified. The aim of this investigation was to examine the effect of the calcimimetic compound NSP R-568 (R-568) on the CaR expression in the parathyroid cells of rats with experimental CRI. Subtotally nephrectomized rats were fed a high-phosphorus diet for 8 (n ϭ 12; Nx-8 group) or 9 wk (n ϭ 11; Nx-9 group) to induce severe SHPT. Another group of uremic rats were fed a high-phosphorus diet for 8 wk and then orally administered R-568 (100 mol/kg body wt) once a day for 7 d (n ϭ 11; NxϩR-568 group). Sham-operated rats that were fed a standard diet for 9 wk were used as controls (n ϭ 8). R-568 treatment induced a significant reduction in plasma PTH level with significant decrease in serum calcium and without change in serum phosphorus concentration. Serum 1,25(OH)2D3 level was not affected by R-568 administration. CaR mRNA and protein levels in the Nx-8 and Nx-9 groups significantly decreased compared with those in the controls; however, no significant difference in these parameters was observed between the Nx-8 and Nx-9 groups. In the NxϩR-568 group, CaR mRNA and protein levels significantly increased compared with those in either the Nx-8 or Nx-9 group. R-568 was effective in reducing the number of proliferating cell nuclear antigen-positive cells along with parathyroid gland growth suppression in the NxϩR-568 group compared with that in the Nx-9 group. The results suggest that the calcimimetic compound R-568 upregulates decreased CaR expression, and the upregulation possibly has an enhancement effect on PTH secretion and parathyroid cell hyperplasia through the improved sensitivity of CaR to [Ca 2ϩ ]o.The parathyroid hormone (PTH) plays a critical role in calcium (Ca) homeostasis and bone mineral metabolism. PTH secretion from parathyroid gland cells is closely regulated by several factors, including serum Ca and phosphorus (P) levels. The calcium-sensing receptor (CaR) on the parathyroid cell surface senses extracellular Ca concentration ([Ca 2ϩ ]o) accurately and mediates PTH synthesis and PTH secretion with other factors, including P and vitamin D (1). It has been reported that the expression levels of the CaR gene and CaR protein are reduced in the parathyroid glands of patients with primary or secondary hyperparathyroidism (SHPT), in which PTH is oversecreted despite normal or high [Ca 2ϩ ]o (2-5). The mechanism underlying the regulation ...

These results suggest that medial layer vascular calcification in uraemic rats with severe hyperphosphataemia and SHPT may be caused in part by Cbfa1 and Pit-1.

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