Serum fibroblast growth factor–21 concentration is associated with residual renal function and insulin resistance in end-stage renal disease patients receiving long-term peritoneal dialysis

Abstract

Fibroblast growth factor–21 (FGF-21) is a new metabolic regulator, which is related to antiobesity and insulin sensitivity in vivo. However, the clinical implication of FGF-21 is poorly understood. To investigate whether FGF-21 may play a role as a metabolic regulator in patients with end-stage renal disease, we measured serum concentrations of FGF-21, inflammatory markers, and metabolic parameters in healthy people (n = 63) and nondiabetic patients receiving peritoneal dialysis (PD, n = 72). The patients were treated with angiotensin receptor blocker for 6 months, and the changes in FGF-21 concentration and metabolic parameters were assessed. Compared with controls, serum FGF-21 concentration was 8 times higher in patients undergoing PD (754.2 ± 463.5 vs 86.9 ± 60.2 pg/mL, P < .001). In controls, only lipid parameters correlated positively with FGF-21 concentration. In contrast, inflammatory markers (interleukin-6, fibrinogen, high-sensitivity C-reactive protein) and homeostasis model assessment of insulin resistance (HOMA-IR) correlated positively and residual renal function correlated inversely with serum FGF-21 concentration in PD patients. In a multivariate analysis adjusting these factors, residual renal function, HOMA-IR, and fibrinogen concentration were independent determinants of serum FGF-21 concentration. After 6-month angiotensin receptor blocker treatment, serum FGF-21 concentration declined significantly by 13% and HOMA-IR and inflammatory markers improved in PD patients. These findings suggest that FGF-21 may play a role in insulin resistance in patients with end-stage renal disease.