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Introduction and Aims: KAI-4169 is a novel peptide agonist of the calcium-sensing receptor (CaSR). Previous studies have demonstrated that KAI-4169 inhibits parathyroid hormone (PTH) secretion in normal animals and in models of chronic kidney disease. The present studies extend these observations by examining the efficacy of KAI-4169 over several weeks on plasma PTH, soft tissue calcification and expression of parathyroid gland vitamin D receptor (VDR) protein in 5/6 nephrectomized rats (5/6 Nx). A comparison between KAI-4169 and cinacalcet was also conducted. Methods: In study #1, rats subjected to 5/6 Nx were treated with KAI-4169 as a thrice weekly subcutaneous bolus at doses of 0.3, 1, 3 mg/kg or vehicle for 6 weeks. In study #2, cinacalcet (10 mg/kg po), saline or KAI-4169 (1 mg/kg iv) was administered daily for 4 weeks post 5/6 Nx. Plasma PTH and serum creatinine were determined at various time points. Assessment of kidney calcification (von Kossa staining) and parathyroid gland VDR protein levels (immunohistochemistry) was performed after sacrifice. Results: 5/6 Nx surgery resulted in increased plasma PTH, increased serum creatinine, decreased parathyroid gland VDR expression and increased soft tissue calcification. Six weeks of treatment with KAI-4169 resulted in a dose-dependent effect on all of these parameters. At six weeks, rats treated with KAI-4169 (3 mg/kg) had reduced PTH (636 vs 1800 pg/mL for KAI-4169 and control, respectively), normalized VDR protein, reduced serum creatinine (1.0 vs 1.6 mg/dL) and reduced kidney calcification (59% reduction vs vehicle). KAI-4169 was tested in a 4-week head-to-head study with cinacalcet to compare effects on PTH. Average baseline PTH values from 5/6 Nx animals prior to dosing was 451 pg/mL. Treatment with KAI-4169 resulted in a significant decrease in PTH compared with the other treatment groups, when measured 16 hours after dosing at the end of each week. PTH in KAI-4169-treated animals ranged from 56 to155 pg/mL (group mean) over the four weeks while vehicle-or cinacalcet-treated animals at the same time points had plasma PTH values ranging from 236-472 and 213-700 pg/mL respectively. Conclusions: KAI-4169 is a novel peptide agonist of the CaSR that reduces PTH levels and improves markers of chronic kidney disease-mineral and bone disorder (CKD-MBD) such as serum creatinine, vascular calcification and expression of VDR in the parathyroid gland. KAI-4169 had a more prolonged pharmacodynamic effect on PTH than cinacalcet. SAO015 EFFECTS OF PHOSPHATE ON VASCULATURE CAN University of GlasgowIntroduction and Aims: Elevated serum phosphate is an independent risk factor for cardiovascular disease although the mechanism of action is unclear. This study looks at the effect of altered phosphate concentration in rat resistance vessels and rat smooth muscle cells (SMCs). Methods: 12 week old male WKY rats were sacrificed. 3rd order resistance vessels were dissected from the mesentery and incubated at 4°C for 16 hours in physiological saline solution (PSS) with normal (...

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Resumo: O estudo investiga os aspectos epidemiológicos da hepatite B em crianças e adolescentes, discutindo os resultados encontrados à luz dos princípios da bioética. Trata-se de um estudo transversal, retrospectivo, com base em uma série temporal

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