Pörsti Ilkka, Fan Meng, Kööbi Peeter, Jolma Pasi, Kalliovalkama Jarkko, Vehmas Tuija I, Helin Heikki, Holthöfer Harry, Mervaala Eero, Nyman Tuulikki, Tikkanen Ilkka
Department of Internal Medicine, University of Tampere, Tampere, Finland.
Kidney Int. 2004 Dec;66(6):2155-66. doi: 10.1111/j.1523-1755.2004.66006.x.
Calcium salts are used as phosphate binders in renal failure, while high calcium diet also improves vasorelaxation and enhances natriuresis. The influences of calcium intake on renal renin-angiotensin system (RAS) are largely unknown.
Four weeks after NTX, rats were put on 3.0% or 0.3% calcium diet for 8 weeks (12-week study). In additional experiments, 15 weeks after NTX, rats were put on similar diets for 12 weeks (27-week study). Appropriate blood, urine, and kidney samples were taken. Renal angiotensin-converting enzyme (ACE) and angiotensin II receptors (AT1, AT2) were examined using autoradiography, ACE also using Western blotting, and connective tissue growth factor (CTGF) using immunohistochemistry.
In the 12-week study, albuminuria increased 5-fold in NTX rats, but only 2-fold in calcium NTX rats on 3.0% calcium. In the 27-week study, high calcium intake decreased blood pressure, retarded progression of renal failure, reduced glomerulosclerosis, interstitial damage, and aortic calcifications, and improved survival from 50% to 92% in NTX rats. In both experiments plasma parathyroid hormone and phosphate were elevated after NTX, and suppressed by high calcium diet, while kidney ACE was down-regulated by 40% or more after increased calcium intake. In the 27-week study renal CTGF was decreased and cortical AT1 receptor density reduced after high calcium diet.
High calcium diet down-regulated kidney ACE, reduced albuminuria and blood pressure, and favorably influenced kidney morphology in experimental renal failure. These findings suggest a link between calcium metabolism and kidney ACE expression, which may play a role in the progression of renal damage.
钙盐在肾衰竭中用作磷结合剂，而高钙饮食也可改善血管舒张并增强利钠作用。钙摄入对肾脏肾素-血管紧张素系统（RAS）的影响在很大程度上尚不清楚。
去甲睾酮（NTX）处理四周后，将大鼠置于含3.0%或0.3%钙的饮食中8周（为期12周的研究）。在额外的实验中，NTX处理15周后，将大鼠置于类似饮食中12周（为期27周的研究）。采集适当的血液、尿液和肾脏样本。使用放射自显影法检测肾脏血管紧张素转换酶（ACE）和血管紧张素II受体（AT1、AT2），使用蛋白质免疫印迹法检测ACE，使用免疫组织化学法检测结缔组织生长因子（CTGF）。
在为期12周的研究中，NTX大鼠的蛋白尿增加了5倍，但在摄入3.0%钙的NTX大鼠中仅增加了2倍。在为期27周的研究中，高钙摄入降低了血压，延缓了肾衰竭进展，减少了肾小球硬化、间质损伤和主动脉钙化，并使NTX大鼠的存活率从50%提高到92%。在两个实验中，NTX后血浆甲状旁腺激素和磷酸盐均升高，并被高钙饮食抑制，而钙摄入增加后肾脏ACE下调40%或更多。在为期27周的研究中，高钙饮食后肾脏CTGF降低，皮质AT1受体密度降低。
高钙饮食下调肾脏ACE，减少蛋白尿和血压，并对实验性肾衰竭的肾脏形态产生有利影响。这些发现表明钙代谢与肾脏ACE表达之间存在联系，这可能在肾损伤进展中起作用。
