Lipid Research Group, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Department of Family and Preventive Medicine, University of California, San Diego, San Diego, CA, USA.
Nephrol Dial Transplant. 2019 Jun 1;34(6):1009-1016. doi: 10.1093/ndt/gfy120.
Fibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA).
The analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73 m2 with eGFR loss rate ≥1 mL/min/1.73 m2 per year) and rapid kidney function decline (eGFR decline >5%/year).
At baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73 m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05).
Our study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.
成纤维细胞生长因子 21(FGF21)可能在慢性肾脏病(CKD)的发生发展中发挥作用。因此,我们在动脉粥样硬化多民族研究(MESA)中调查了血浆 FGF21 水平与肾功能和白蛋白尿的关系。
本分析纳入了 2000 年至 2002 年间年龄在 45-84 岁之间、无明显临床心血管疾病(CVD)的 5724 名 MESA 参与者。在 10 年期间的 4 次额外临床随访中对参与者进行了随访。在基线检查时,通过酶联免疫吸附试验测量血浆 FGF21 水平。肾功能通过估计肾小球滤过率(eGFR)评估。结果为尿白蛋白:肌酐比值(UACR)进展、通过 eGFR 确定的新发 CKD(eGFR 下降率≥1mL/min/1.73m2/年,达到 eGFR<60mL/min/1.73m2)和肾功能快速下降(eGFR 下降>5%/年)。
在基线时,经过调整人口统计学、社会经济和其他混杂因素后,FGF21 水平越高,以连续和分类四分位数变量评估,eGFR 越低,UACR 越高[最高 FGF21 四分位数与最低四分位数相比,eGFR 差异为-2.63mL/min/1.73m2,对数正态转换的 UACR(mg/g)差异为 0.134,均 P<0.001]。然而,在纵向分析中,基线 FGF21 水平不能预测通过 eGFR 确定的新发 CKD、肾功能快速下降或 UACR 进展。未发现与性别和种族/民族之间存在显著交互作用(均 P>0.05)。
我们的研究不支持 FGF21 作为基线时无明显临床 CVD 的成年人肾功能下降或白蛋白尿的预测生物标志物。