Lee C H, Hui E Y L, Woo Y C, Yeung C Y, Chow W S, Yuen M M A, Fong C H Y, Xu A, Lam K S L
Department of Medicine (C.H.L., E.Y.L.H., Y.C.W., C.Y.Y., W.S.C., M.M.A.Y., C.H.Y.F. A.X., K.S.L.L.), Queen Mary Hospital, Hong Kong SAR; Research Centre of Heart, Brain, Hormone and Healthy Aging (E.Y.L.H., A.X., K.S.L.L.), The University of Hong Kong, Pokfulam, Hong Kong SAR; and State Key Laboratory of Pharmaceutical Biotechnology (A.X., K.S.L.L.), The University of Hong Kong, Pokfulam, Hong Kong SAR.
J Clin Endocrinol Metab. 2015 Apr;100(4):1368-75. doi: 10.1210/jc.2014-3465. Epub 2015 Jan 27.
Elevated fibroblast growth factor 21 (FGF21) levels have been suggested, from cross-sectional studies, as an indicator of subclinical diabetic nephropathy. We investigated whether serum FGF21 was predictive of the development of diabetic nephropathy.
Baseline serum FGF21 levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of serum FGF21 in predicting decline in estimated glomerular filtration rate (eGFR) over a median follow-up of 4 years was analyzed using Cox regression analysis.
At baseline, serum FGF21 levels increased progressively with eGFR category (P for trend <.001). Among 1071 subjects with baseline eGFR ≥ 30 mL/min/1.73 m(2), serum FGF21 levels were significantly higher in those with eGFR decline during follow-up (n = 171) than those without decline (n = 900) (P < .001). In multivariable Cox regression analysis, baseline serum FGF21 was independently associated with eGFR decline (hazard ratio, 1.21; 95% confidence interval [CI], 1.01-1.43; P = .036), even after adjustment for baseline eGFR. In a subgroup of 559 subjects with baseline eGFR ≥ 60 mL/min/1.73 m(2) and normoalbuminuria, serum FGF21 level remained an independent predictor of eGFR decline (hazard ratio, 1.36; 95% CI, 1.06-1.76; P = .016). Integrated discrimination improvement (IDI) suggested that the inclusion of baseline serum FGF21 significantly improved the prediction of eGFR decline (IDI, 1%; 95% CI, 0.1-3.0; P = .013) in this subgroup, but not in the initial cohort involving all subjects.
Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy.
横断面研究表明，成纤维细胞生长因子21（FGF21）水平升高是亚临床糖尿病肾病的一个指标。我们研究了血清FGF21是否可预测糖尿病肾病的发生。
对从香港西区糖尿病登记处招募的1136名中国2型糖尿病患者测量基线血清FGF21水平。使用Cox回归分析来分析血清FGF21在预测4年中位随访期内估计肾小球滤过率（eGFR）下降中的作用。
在基线时，血清FGF21水平随eGFR类别逐渐升高（趋势P<.001）。在1071名基线eGFR≥30 mL/min/1.73 m²的受试者中，随访期间eGFR下降者（n = 171）的血清FGF21水平显著高于未下降者（n = 900）（P<.001）。在多变量Cox回归分析中，即使在调整了基线eGFR后，基线血清FGF21仍与eGFR下降独立相关（风险比，1.21；95%置信区间[CI]，1.01 - 1.43；P = .036）。在559名基线eGFR≥60 mL/min/1.73 m²且尿白蛋白正常的受试者亚组中，血清FGF21水平仍是eGFR下降的独立预测因素（风险比，1.36；95%CI，1.06 - 1.76；P = .016）。综合判别改善（IDI）表明，纳入基线血清FGF21显著改善了该亚组中eGFR下降的预测（IDI，1%；95%CI，0.1 - 3.0；P = .013），但在涉及所有受试者的初始队列中未改善。
血清FGF21水平升高可能是预测肾脏疾病进展的有用生物标志物，尤其是在糖尿病肾病的早期阶段。
