Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Metabolism. 2010 Nov;59(11):1656-62. doi: 10.1016/j.metabol.2010.03.018. Epub 2010 Apr 27.
Fibroblast growth factor-21 (FGF-21) is a new metabolic regulator, which is related to antiobesity and insulin sensitivity in vivo. However, the clinical implication of FGF-21 is poorly understood. To investigate whether FGF-21 may play a role as a metabolic regulator in patients with end-stage renal disease, we measured serum concentrations of FGF-21, inflammatory markers, and metabolic parameters in healthy people (n = 63) and nondiabetic patients receiving peritoneal dialysis (PD, n = 72). The patients were treated with angiotensin receptor blocker for 6 months, and the changes in FGF-21 concentration and metabolic parameters were assessed. Compared with controls, serum FGF-21 concentration was 8 times higher in patients undergoing PD (754.2 ± 463.5 vs 86.9 ± 60.2 pg/mL, P < .001). In controls, only lipid parameters correlated positively with FGF-21 concentration. In contrast, inflammatory markers (interleukin-6, fibrinogen, high-sensitivity C-reactive protein) and homeostasis model assessment of insulin resistance (HOMA-IR) correlated positively and residual renal function correlated inversely with serum FGF-21 concentration in PD patients. In a multivariate analysis adjusting these factors, residual renal function, HOMA-IR, and fibrinogen concentration were independent determinants of serum FGF-21 concentration. After 6-month angiotensin receptor blocker treatment, serum FGF-21 concentration declined significantly by 13% and HOMA-IR and inflammatory markers improved in PD patients. These findings suggest that FGF-21 may play a role in insulin resistance in patients with end-stage renal disease.
成纤维细胞生长因子 21(FGF-21)是一种新的代谢调节剂,与体内的抗肥胖和胰岛素敏感性有关。然而,FGF-21 的临床意义尚不清楚。为了研究 FGF-21 是否可能在终末期肾病患者中作为代谢调节剂发挥作用,我们测量了健康人(n=63)和接受腹膜透析(PD,n=72)的非糖尿病患者的血清 FGF-21 浓度、炎症标志物和代谢参数。患者接受血管紧张素受体阻滞剂治疗 6 个月,并评估 FGF-21 浓度和代谢参数的变化。与对照组相比,PD 患者的血清 FGF-21 浓度高 8 倍(754.2±463.5 与 86.9±60.2 pg/mL,P<.001)。在对照组中,只有脂质参数与 FGF-21 浓度呈正相关。相比之下,炎症标志物(白细胞介素-6、纤维蛋白原、高敏 C 反应蛋白)和稳态模型评估的胰岛素抵抗(HOMA-IR)与 PD 患者的血清 FGF-21 浓度呈正相关,而残余肾功能与血清 FGF-21 浓度呈负相关。在调整这些因素的多元分析中,残余肾功能、HOMA-IR 和纤维蛋白原浓度是血清 FGF-21 浓度的独立决定因素。在接受 6 个月的血管紧张素受体阻滞剂治疗后,PD 患者的血清 FGF-21 浓度显著下降 13%,HOMA-IR 和炎症标志物得到改善。这些发现表明 FGF-21 可能在终末期肾病患者的胰岛素抵抗中发挥作用。