title: Impaired postprandial fibroblast growth factor (FGF)-19 response in patients with stage 5 chronic kidney diseases is ameliorated following antioxidative therapy.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Renal Research Group, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Ewa
authors.initials: E
authors.lastname: Ellis
authors.forename: Jonas
authors.initials: J
authors.lastname: Axelsson
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D029798:Blueberry Plants; D016022:Case-Control Studies; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy; D019518:Postprandial Period; D011379:Prognosis; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000628:therapy*; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D001786:Blood Glucose; C117476:FGF19 protein, human; D007328:Insulin; D014280:Triglycerides; D005346:Fibroblast Growth Factors; D000111:Acetylcysteine
keywords: CKD; FGF-19; MP865; N-acetyl cysteine; glucose; hormones; insulin resistance; postprandial