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

Summary 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.