Nagano N, Miyata S, Obana S, Ozai M, Kobayashi N, Fukushima N, Burke S K, Wada M
Pharmaceutical Development Laboratories, Kirin Brewery Co., Ltd, 3 Miyahara-cho, Takasaki-shi, Gunma 370-1295, Japan.
Nephrol Dial Transplant. 2001 Sep;16(9):1870-8. doi: 10.1093/ndt/16.9.1870.
It has been demonstrated that dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI) independently of serum calcium and 1,25(OH)(2)D3 levels. This study was conducted to examine whether sevelamer hydrochloride (Renagel); hereafter referred to as sevelamer), a non-calcaemic phosphate binder could inhibit the parathyroid gland (PTG) hyperplasia in rats with progressive CRI.
Male Sprague-Dawley rats were injected twice with low doses of adriamycin (ADR). Two weeks after the last injection of ADR, rats were fed a diet containing 1 or 3% sevelamer for 84 days. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of study, serum 1,25(OH)(2)D3 levels were measured and the maximal two-dimension area of the PTG in paraffin section was calculated using an imaging analyser.
Dietary sevelamer treatment inhibited the elevations of serum phosphorus, calciumxphosphorus product, and PTH levels that occurred as the study progressed. Sevelamer also suppressed maximal PTG area and there existed positive strong correlation between maximal PTG area and serum PTH levels at the end of the study. Serum phosphorus levels positively correlated well with serum PTH levels and maximal PTG area. In contrast, serum calcium or 1,25(OH)(2)D3 levels did not show any correlation with serum PTH levels and maximal PTG area.
Sevelamer treatment arrested hyperphosphataemia and PTG hyperplasia accompanied by the elevation of serum PTH levels. The correlation analysis suggests that reduced serum phosphorus levels contributed to the suppression of PTG hyperplasia and resulted in the reduction of PTH levels in this animal model after the sevelamer treatment. The management of phosphorus control started from early stage of CRI could prevent PTG hyperplasia and facilitate later management of secondary hyperparathyroidism.
业已证明，饮食中限制磷可抑制慢性肾功能不全（CRI）实验动物的甲状旁腺激素（PTH）分泌及甲状旁腺细胞增殖，且与血清钙和1,25(OH)₂D₃水平无关。本研究旨在探讨非含钙磷结合剂碳酸司维拉姆（Renagel，以下简称司维拉姆）是否能抑制进行性CRI大鼠的甲状旁腺（PTG）增生。
对雄性Sprague-Dawley大鼠两次注射低剂量阿霉素（ADR）。最后一次注射ADR两周后，给大鼠喂食含1%或3%司维拉姆的饲料，持续84天。测定血清钙、磷和PTH水平的时间进程变化。研究结束时，测定血清1,25(OH)₂D₃水平，并使用图像分析仪计算石蜡切片中PTG的最大二维面积。
饮食中司维拉姆治疗可抑制随着研究进展出现的血清磷、钙磷乘积和PTH水平升高。司维拉姆还可抑制PTG最大面积，且研究结束时PTG最大面积与血清PTH水平之间存在强正相关。血清磷水平与血清PTH水平及PTG最大面积呈良好正相关。相比之下，血清钙或1,25(OH)₂D₃水平与血清PTH水平及PTG最大面积无任何相关性。
司维拉姆治疗可阻止高磷血症及PTG增生，并伴有血清PTH水平升高。相关性分析表明，血清磷水平降低有助于抑制PTG增生，并导致司维拉姆治疗后该动物模型中PTH水平降低。从CRI早期开始控制磷可预防PTG增生，并有助于后期继发性甲状旁腺功能亢进的管理。
