Impaired postprandial fibroblast growth factor (FGF)-19 response in patients with stage 5 chronic kidney diseases is ameliorated following antioxidative therapy.

Background: While dysmetabolism is common in patients with chronic kidney disease (CKD) and associated with mortality, the mechanisms mediating these changes are unclear. New data implicate fibroblast growth factor (FGF)-19 as a possible entero-hepatic modulator of lipid metabolism.

Methods: Using samples previously gathered as part of a randomized placebo-controlled study of antioxidative therapy for postprandial dysmetabolism, we investigated short-term (4 h) postprandial changes in circulating FGF-19 (ELISA) and the relationship to metabolic markers in six haemodialysis (HD) patients and nine matched healthy subjects (HS), with each participant assessed on four separate occasions.

Results: The postprandial FGF-19 response was blunted in patients [maximum change +34.63 (0.24-186) pg/mL] versus controls [maximum change +150.3 (31.2-378.7) pg/mL; P < 0.0001], and the area under the curve (AUC; pg × min × mL(-1)) was also significantly lower 18 019 (12 513-44 387) versus 38 517 (19 775-72 816; P < 0.01). In patients, we found univariate correlations between AUC FGF-19 with AUC C-peptide (rho = 0.71; P = 0.001), AUC insulin (rho = 0.63; P = 0.001), but not with AUCs for triglycerides (TG) or glucose. Finally, treatment with the antioxidative compounds N-acetyl cysteine or MP865, but not with placebo, was associated with higher plasma FGF-19 (NAC and MP865 coefficients -0.28 and -0.23, P < 0.05, respectively).

Conclusion: In advanced CKD, the postprandial FGF-19 response appears to be blunted, with partial normalization following antioxidative treatments. A blunted FGF-19 response was associated with impaired insulin and C-peptide signalling.