Divisions of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
J Nephrol. 2019 Feb;32(1):93-100. doi: 10.1007/s40620-018-0559-2. Epub 2018 Nov 21.
Cardiovascular (CV) complications are common in chronic kidney disease (CKD). Numerous metabolic disturbances including hyperphosphatemia, high circulating calciprotein particles (CPP), hyperparathyroidism, metabolic acidosis, and magnesium deficiency are associated with, and likely pathogenic for CV complications in CKD. The goal of this feasibility study was to determine whether effervescent calcium magnesium citrate (EffCaMgCit) ameliorates the aforementioned pathogenic intermediates.
Nine patients with Stage 3 and nine patients with Stage 5D CKD underwent a randomized crossover study, where they took EffCaMgCit three times daily for 7 days in one phase, and a conventional phosphorus binder calcium acetate (CaAc) three times daily for 7 days in the other phase. Two-hour postprandial blood samples were obtained on the day before and on the 7th day of treatment.
In Stage 5D CKD, EffCaMgCit significantly increased T50 (half time for conversion of primary to secondary CPP) from baseline by 63% (P = 0.013), coincident with statistically non-significant declines in serum phosphorus by 25% and in saturation of octacalcium phosphate by 35%; CaAc did not change T50. In Stage 3 CKD, neither EffCaMgCit nor CaAc altered T50. With EffCaMgCit, a significant increase in plasma citrate was accompanied by statistically non-significant increase in serum Mg and phosphate. CaAc was without effect in any of these parameters in Stage 3 CKD. In both Stages 3 and 5D, both drugs significantly reduced serum parathyroid hormone. Only EffCaMgCit significantly increased serum bicarbonate by 3 mM (P = 0.015) in Stage 5D.
In Stage 5D, EffCaMgCit inhibited formation of CPP, suppressed PTH, and conferred magnesium and alkali loads. These effects were unique, since they were not observed with CaAc. In Stage 3 CKD, neither of the regimens have any effect. These metabolic changes suggest that EffCaMgCit might be useful in protecting against cardiovascular complications of CKD by ameliorating pathobiologic intermediates.
心血管（CV）并发症在慢性肾脏病（CKD）中很常见。许多代谢紊乱，包括高磷血症、高循环钙磷蛋白颗粒（CPP）、甲状旁腺功能亢进、代谢性酸中毒和镁缺乏，与 CKD 的 CV 并发症有关，并且可能是其致病因素。本可行性研究的目的是确定泡腾钙镁柠檬酸盐（EffCaMgCit）是否能改善上述致病因素。
9 名处于 3 期和 9 名处于 5D 期的 CKD 患者进行了随机交叉研究，在一个阶段中每天服用 EffCaMgCit 三次，在另一个阶段中每天服用传统的磷结合剂醋酸钙（CaAc）三次，持续 7 天。在治疗前一天和第 7 天采集两小时餐后血样。
在 5D 期 CKD 中，EffCaMgCit 使 T50（初级 CPP 转化为次级 CPP 的半衰期）从基线增加了 63%（P=0.013），同时血清磷下降了 25%，八钙磷酸盐饱和度下降了 35%；CaAc 没有改变 T50。在 3 期 CKD 中，EffCaMgCit 和 CaAc 均未改变 T50。使用 EffCaMgCit，血浆柠檬酸盐显著增加，同时血清镁和磷略有增加。在 3 期 CKD 中，CaAc 对这些参数均无影响。在两期 CKD 中，两种药物均显著降低血清甲状旁腺激素。只有 EffCaMgCit 使 5D 期血清碳酸氢盐显著增加 3mM（P=0.015）。
在 5D 期，EffCaMgCit 抑制 CPP 的形成，抑制 PTH，并提供镁和碱负荷。这些作用是独特的，因为它们在使用 CaAc 时没有观察到。在 3 期 CKD 中，两种方案均无作用。这些代谢变化表明，EffCaMgCit 通过改善病理生理中间产物，可能对保护 CKD 的心血管并发症有用。
