Serum levels of fibroblast growth factor-21 are increased in chronic and acute renal dysfunction.

OBJECTIVE: Fibroblast growth factor (FGF)-21 has recently been introduced as a circulating adipokine which reverses insulin resistance and obesity in rodents. In this study, regulation of FGF-21 in renal dysfunction was elucidated in both chronic kidney disease (CKD) and acute kidney dysfunction (AKD).

STUDY DESIGN AND METHODS: Serum concentrations of total FGF-21 were quantified by enzyme-linked immunosorbent assay in 499 patients with CKD stages 1-5 (study population 1). Furthermore, total FGF-21 was determined before and within 30 h after unilateral nephrectomy, a model of AKD, in 32 patients (study population 2). FGF-21 levels were correlated to anthropometric and biochemical parameters of renal function, glucose and lipid metabolism, as well as inflammation, in both studies.

RESULTS: In study population 1, median [interquartile range] circulating FGF-21 adjusted for age, gender and body mass index was significantly different between CKD stages with highest values detectable in stage 5 (stage 1: 86·4 [132·9]; 2: 206·4 [223·1]; 3: 289·8 [409·3]; 4: 591·3 [789·0]; 5: 1918·1 [4157·0] ng/l). Furthermore, estimated glomerular filtration rate remained a strong independent and negative predictor of FGF-21. In study population 2, FGF-21 increased significantly postsurgically (325·0 [984·0] ng/l) as compared to presurgical values (255·5 [243·0] ng/l). Furthermore, relative changes of FGF-21 were independently and positively predicted by relative changes of creatinine.

CONCLUSIONS: We demonstrate that circulating FGF-21 is increased in both CKD and AKD. Our results suggest renal excretion as a major route for FGF-21 elimination. The pathophysiological significance of these findings needs to be elucidated in more detail.