Circulating Fibroblast Growth Factor 21 Levels Predict Progressive Kidney Disease in Subjects With Type 2 Diabetes and Normoalbuminuria

• Published in: The journal of clinical endocrinology and metabolism Vol. 100; no. 4; pp. 1368 - 1375
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.04.2015; Copyright by The Endocrine Society
• Subjects: Adult; Aged; Albuminuria - blood; Albuminuria - diagnosis; Cross-Sectional Studies; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - epidemiology; Diabetic Nephropathies - blood; Diabetic Nephropathies - diagnosis; Diabetic Nephropathies - epidemiology; Diabetic nephropathy; Disease Progression; Epidermal growth factor receptors; Female; Fibroblast Growth Factors - blood; Fibroblasts; Glomerular filtration rate; Growth factors; Hong Kong - epidemiology; Humans; Kidney diseases; Male; Middle Aged; Nephropathy; Predictive Value of Tests; Prognosis; Registries; Regression analysis; Hong Kong
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2014-3465

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.Method: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.Results: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 m2, 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 m2 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.Conclusions:Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy.