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 30h 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 center dot 4 [132 center dot 9]; 2: 206 center dot 4 [223 center dot 1]; 3: 289 center dot 8 [409 center dot 3]; 4: 591 center dot 3 [789 center dot 0]; 5: 1918 center dot 1 [4157 center dot 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 center dot 0 [984 center dot 0] ng/l) as compared to presurgical values (255 center dot 5 [243 center dot 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.