Ennis Jennifer L, Worcester Elaine M, Coe Fredric L, Sprague Stuart M
Litholink® Corporation, 2250 W. Campbell Park Drive, Chicago, IL, 60612, USA.
Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL, USA.
J Nephrol. 2016 Feb;29(1):63-70. doi: 10.1007/s40620-015-0186-0. Epub 2015 Mar 4.
It is uncertain whether increasing 25-hydroxyvitamin D (25-D) levels in chronic kidney disease (CKD) patients above those recommended by current guidelines result in progressive amelioration of secondary hyperparathyroidism. Our objective was to identify a potential therapeutic 25-D target which optimally lowers plasma parathyroid hormone (PTH) without producing excessive hypercalcemia or hyperphosphatemia in CKD.
We performed a cross-sectional analysis of 14,289 unselected stage 1-5 CKD patients from US primary care and nephrology practices utilizing a laboratory-based CKD clinical decision support service between September 2008 and May 2012. Estimated glomerular filtration rate (eGFR), plasma PTH, and serum 25-D, calcium, and phosphorus results were analyzed.
In CKD stages 3-5, progressively higher 25-D pentiles contained progressively lower mean PTH levels. Regression analysis of log PTH on 25-D was significant in all CKD stages with no evidence of a decreasing effect of 25-D to lower PTH until 25-D levels of 42-48 ng/ml. Progressively higher 25-D concentrations were not associated with increased rates of hypercalcemia or hyperphosphatemia.
We found evidence for an optimal level of 25-D above which suppression of PTH progressively diminishes. This level is more than twice that currently recommended for the general population. We found no association between these higher 25-D levels and hyperphosphatemia or hypercalcemia. Additional prospective trials seem appropriate to test the idea that 25-D levels around 40-50 ng/ml could be a safe and effective treatment target for secondary hyperparathyroidism in CKD.
慢性肾脏病（CKD）患者将25-羟维生素D（25-D）水平提升至高于现行指南推荐水平是否会使继发性甲状旁腺功能亢进逐渐改善尚不确定。我们的目的是确定一个潜在的治疗性25-D目标，该目标能在CKD患者中最佳地降低血浆甲状旁腺激素（PTH）水平，同时又不会导致过度的高钙血症或高磷血症。
我们对2008年9月至2012年5月期间利用基于实验室的CKD临床决策支持服务从美国初级保健和肾脏病诊疗机构选取的14289例未经挑选的1-5期CKD患者进行了横断面分析。分析了估计肾小球滤过率（eGFR）、血浆PTH以及血清25-D、钙和磷的检测结果。
在CKD 3-5期，25-D五分位数越高，平均PTH水平越低。在所有CKD分期中，log PTH对25-D的回归分析均具有显著性，直到25-D水平达到42-48 ng/ml时才有证据表明25-D降低PTH的作用减弱。25-D浓度逐渐升高与高钙血症或高磷血症发生率增加无关。
我们发现有证据表明存在一个25-D的最佳水平，高于此水平，PTH的抑制作用会逐渐减弱。该水平是目前针对普通人群推荐水平的两倍多。我们发现这些较高的25-D水平与高磷血症或高钙血症之间没有关联。进行更多前瞻性试验似乎有助于验证以下观点，即25-D水平在40-50 ng/ml左右可能是CKD继发性甲状旁腺功能亢进的一个安全有效的治疗靶点。
