FGF-21 CORRELATES WITH OVERHYDRATION: IS THERE A ROLE FOR PERITONEAL GLUT-1?

Abstract BACKGROUND AND AIMS FGF-21 is a hepatokine that stimulates glucose uptake through GLUT-1. The presence of this glucose transporter in peritoneal fibroblasts is driven by peritoneal glucose exposure and is related to impaired ultrafiltration, predisposing to overhydration. The study was designed to determine FGF-21 levels in peritoneal effluent and serum, and its possible association with overhydration. METHOD Prevalent and incident peritoneal dialysis (PD) patients without diabetes were included. FGF-21 (dialysate and serum) was obtained during a 3.86% glucose peritoneal equilibration test. Peritoneal glucose load was calculated. The presence or absence of local peritoneal production was assessed by comparing the dialysate to plasma (D/P) ratio of FGF-21 (MW 32 kD) with that of albumin (MW 67 kD). Hydration status was assessed by bioimpedance. Spearman's correlations were performed. RESULTS A total of 58 patients (38 incident, 20 prevalent) were included, mean age 54 years, 67% males, PD duration from 1 to 75 months, mean 10.4. Residual GFR was 6.4 ± 3.5 mL/min/1.73 m2 and D/P creatinine 0.65 ± 0.12. Peritoneal glucose load was 110.5 g/day (range 40.8–226.9). Dialysate FGF-21 was 42.5 ± 47.0 pg/mL and serum FGF-21 943.9 ± 1164.8 pg/mL, giving a D/P ratio of 0.07. D/P albumin was 0.009, indicating that dialysate FGF-21 concentrations can be explained by transport from the circulation, without local peritoneal production. Serum FGF-21 was positively correlated with dialysate FGF-21, extracellular water excess and total peritoneal glucose load (all P < 0.01). Some association was present with PD duration (P < 0.05). No relationship was found between plasma FGF-21 and plasma insulin, D/P creatinine, or residual kidney function. CONCLUSION FGF-21 in peritoneal effluent is likely not locally produced, but caused by transport from the circulation. The associations between plasma FGF-21 levels with PD duration, peritoneal glucose load and overhydration, all indicate an effect of peritoneal glucose absorption from the peritoneal cavity into the interstitium with an insulin-independent storage into interstitial adipocytes, where it may stimulate the expression of GLUT-1.