Division of Internal Medicine, Inoue Hospital, 16-17, Enoki-cho, Suita, Osaka, Japan.
Department of Vascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan.
Nephrol Dial Transplant. 2023 Mar 31;38(4):1002-1008. doi: 10.1093/ndt/gfac222.
Hyperphosphatemia is a risk factor for cardiovascular outcomes in patients with chronic kidney disease. In an experimental model, hyperphosphatemia promoted atherosclerosis by activating sterol regulatory element-binding protein 2, which controls cholesterol homeostasis. In the present study, we hypothesized that serum phosphate level is associated with cholesterol metabolism in patients with kidney failure.
We conducted a single-center cross-sectional study including 492 patients undergoing hemodialysis and 100 healthy controls not on statin or ezetimibe treatment. Serum lathosterol and campesterol levels were measured as a marker of cholesterol synthesis and absorption, respectively. As compared with the control group, the hemodialysis patients had higher median phosphate {5.8 mg/dL [interquartile range (IQR 5.0-6.6) versus 3.3 (3.0-3.6); P < .001], lower lathosterol [1.2 µg/mL (IQR 0.8-1.7) versus 2.6 (1.9-3.4); P < .001] and higher campesterol levels [4.5 µg/mL (IQR 3.6-6.0) versus 4.1 (3.2-5.4); P = .02]. Serum phosphate correlated positively to campesterol in the control group (Spearman's r = 0.21, P = .03) and in hemodialysis patients (Spearman's r = 0.19, P < .001). The positive association between phosphate and campesterol levels in the hemodialysis group remained significant in multivariable-adjusted linear regression analysis. There was no significant association between phosphate and lathosterol in either group.
An independent association was found between phosphate and campesterol levels in patients with kidney failure. This study suggests a novel relationship between phosphate and cholesterol metabolism, both of which could affect cardiovascular outcomes in this population.
高磷血症是慢性肾脏病患者心血管结局的一个危险因素。在一个实验模型中，高磷血症通过激活固醇调节元件结合蛋白 2 促进动脉粥样硬化，后者控制胆固醇的体内平衡。在本研究中，我们假设血清磷酸盐水平与肾衰竭患者的胆固醇代谢有关。
我们进行了一项单中心横断面研究，纳入了 492 名正在接受血液透析的患者和 100 名未接受他汀类药物或依折麦布治疗的健康对照者。血清羊毛固醇和菜油固醇水平分别作为胆固醇合成和吸收的标志物进行测量。与对照组相比，血液透析患者的磷酸盐中位数更高[5.8 mg/dL（四分位距 5.0-6.6）比 3.3（3.0-3.6）；P<.001]，羊毛固醇更低[1.2 µg/mL（四分位距 0.8-1.7）比 2.6（1.9-3.4）；P<.001]，菜油固醇水平更高[4.5 µg/mL（四分位距 3.6-6.0）比 4.1（3.2-5.4）；P=.02]。在对照组（Spearman's r = 0.21，P =.03）和血液透析患者中（Spearman's r = 0.19，P<.001），血清磷酸盐与菜油固醇水平呈正相关。在多变量调整的线性回归分析中，血液透析患者组中磷酸盐与菜油固醇水平之间的正相关关系仍然显著。在两组中，磷酸盐与羊毛固醇之间均无显著相关性。
在肾衰竭患者中发现磷酸盐与菜油固醇水平之间存在独立的关联。本研究提示了磷酸盐与胆固醇代谢之间的一种新关系，这两者均可能影响该人群的心血管结局。
