晚期慢性肾脏病患者硫酸吲哚酚与成纤维细胞生长因子 23 的相关性。

Association of indoxyl sulfate with fibroblast growth factor 23 in patients with advanced chronic kidney disease.

机构信息

Division of Nephrology, Department of Internal Medicine (C-JL, C-FP, H-HC, C-JW), Department of Medical Research (F-JS), Department of Laboratory Medicine (T-JW) and Division of Genetics and Metabolism, Department of Medical Research (C-KC), Mackay Memorial Hospital, Taipei, Taiwan; Mackay Medicine (C-JL, C-FP, F-JS, H-HC, C-JW), Nursing and Management College, Taipei, Taiwan; Institute of Biotechnology (C-JL, C-KC, H-LL), National Taipei University of Technology, Taipei, Taiwan; College of Medicine (C-KC), Fu-Jen Catholic University, New Taipei City, Taiwan; and Graduate Institute of Medical Science (C-JW), Taipei Medical University, Taipei, Taiwan.

出版信息

Am J Med Sci. 2014 May;347(5):370-6. doi: 10.1097/MAJ.0b013e3182989f26.

DOI:10.1097/MAJ.0b013e3182989f26

PMID:24051956

Abstract

BACKGROUND

Protein-bound uremic toxins-indoxyl sulfate (IS) and p-cresyl sulfate (PCS)-can not only predict clinical outcomes but also may relate to bone-mineral disorders in patients with chronic kidney disease (CKD). However, the relationship between protein-bound uremic toxins and fibroblast growth factor 23 (FGF23) has not been studied before. The objective of this study was to explore the association of IS and PCS with FGF23 in a CKD-based cohort.

METHODS

This is a cross-sectional study that enrolled 80 stable CKD stage 3 to 5 patients who met the inclusion criteria in a single medical center. Serum levels of IS, PCS and FGF23 were measured concurrently. General biochemistry and patient background were also investigated.

RESULTS

Serum FGF23 and IS concentrations were elevated commensurately with deteriorating renal function. Pearson's analysis showed that FGF23 levels were significantly associated with blood urea nitrogen (r = 0.381, P < 0.05), creatinine (r = 0.632, P < 0.01), estimated glomerular filtration rate (r = -0.447, P < 0.05), phosphate (r = 0.543, P < 0.01), intact parathyroid hormone (r = 0.543, P < 0.01), IS (r = 0.432, P < 0.01) and PCS (r = 0.318, P < 0.05). After adjusting other confounding factors by stepwise multiple linear regression analysis, only creatinine (β = 0.82, P < 0.01), phosphate (β = 0.28, P = 0.02) and IS (β = 0.39, P = 0.04) retained statistically significant associations with FGF23. Moreover, serum levels of IS were higher in patients with high FGF23 concentration (>90 pg/mL, median value) than those with lower FGF23 (P < 0.01).

CONCLUSIONS

Results indicated that only IS but not PCS correlated independently with FGF23 in worsening CKD. IS may be an independent factor involved in regulation of bone-mineral metabolism.

摘要

背景

蛋白结合型尿毒症毒素-吲哚硫酸酯（IS）和对甲酚硫酸酯（PCS）不仅可以预测临床结局，而且可能与慢性肾脏病（CKD）患者的矿物质骨代谢紊乱有关。然而，蛋白结合型尿毒症毒素与成纤维细胞生长因子 23（FGF23）之间的关系尚未被研究。本研究旨在探讨基于 CKD 队列中 IS 和 PCS 与 FGF23 的相关性。

方法

这是一项横断面研究，纳入了在一家医疗中心符合纳入标准的 80 名稳定的 CKD 3 至 5 期患者。同时检测血清 IS、PCS 和 FGF23 水平。还调查了一般生化和患者背景。

结果

血清 FGF23 和 IS 浓度随肾功能恶化而升高。Pearson 分析显示，FGF23 水平与血尿素氮（r = 0.381，P < 0.05）、肌酐（r = 0.632，P < 0.01）、估算肾小球滤过率（r = -0.447，P < 0.05）、磷酸盐（r = 0.543，P < 0.01）、全段甲状旁腺激素（r = 0.543，P < 0.01）、IS（r = 0.432，P < 0.01）和 PCS（r = 0.318，P < 0.05）呈显著相关。通过逐步多元线性回归分析调整其他混杂因素后，仅肌酐（β = 0.82，P < 0.01）、磷酸盐（β = 0.28，P = 0.02）和 IS（β = 0.39，P = 0.04）与 FGF23 仍有统计学意义。此外，高 FGF23 浓度（>90 pg/mL，中位数）患者的血清 IS 水平高于低 FGF23 浓度患者（P < 0.01）。