Changes in FGF-23, Neutrophil/Platelet Activation Markers, and Angiogenin in Advanced Chronic Kidney Disease and Their Effect on Arterial Stiffness

Abstract

Aims: The aims of this study were to measure changes in fibroblast growth factor 23 (FGF-23), neutrophil (elastase, lactoferrin)/platelet activation marker (mean platelet volume-to-platelet count ratio [MPR]), and angiogenin according to the stage of chronic kidney disease (CKD), and to evaluate the association of FGF-23, elastase, lactoferrin, MPR, and angiogenin with arterial stiffness using brachial-ankle pulse wave velocity (ba-PWV) in CKD patients. Methods: According to the estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the patients were allocated to five groups: (1) normal controls (eGFR >= 90 mL/min/1.73 m(2) without pathologic, urine [proteinuria], blood [electrolyte], and imaging abnormalities; n = 22); (2) CKD stage 2 (eGFR 60-89 mL/min/1.73 m(2); n = 17); (3) CKD stage 3 (eGFR 30-59 mL/min/1.73 m(2); n = 22); (4) CKD stage 4 (eGFR 15-30 mL/min/1.73 m(2); n = 17); and (5) CKD stage 5-hemodialysis (HD) (n = 30). All the patients were free of clinically apparent cardiovascular disease. Serum FGF-23, elastase, lactoferrin, and angiogenin concentrations and the MPR were measured to study the association of the above parameters with the clinical (age, sex, presence of diabetes mellitus, and blood pressure), biochemical (calcium, phosphorus, uric acid, intact parathyroid hormone [PTH], low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein), and ba-PWV values of the CKD patients. Results: (1) The mean ba-PWV values were 1,497.2 +/- 206.4 cm/s in the controls, 1,649.0 +/- 247.9 cm/s in the CKD stage 2 group (p < 0.05 vs. controls), 1,655.8 +/- 260.3 cm/s in the CKD stage 3 group (p < 0.05 vs. controls), 1,823.0 +/- 402.4 cm/s in the CKD stage 4 group (p < 0.05 vs. controls and CKD stages 2 and 3), and 1,905.2 +/- 374.1 cm/s in the CKD stage 5-HD group (p < 0.05 vs. controls and CKD stage 2). (2) The mean log(10)(FGF-23) concentration values were 0.77 +/- 0.27, 0.97 +/- 0.48, 1.10 +/- 0.35 (p < 0.05 vs. controls and CKD stage 2), 1.35 +/- 0.48 (p < 0.05 vs. controls and CKD stages 2 and 3), and 2.12 +/- 0.82 (p < 0.05 vs. controls and CKD stages 2-4); the mean angiogenin levels were 230.6 +/- 70.5 pg/mL, 283.0 +/- 53.5 pg/mL (p < 0.05 vs. controls), 347.3 +/- 76.9 pg/mL (p < 0.05 vs. controls and CKD stage 2), 445.9 +/- 90.6 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3), and 370.9 +/- 142.4 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3). (3) In the stage 3-4 CKD/HD patients, the mean elastase-to-neutrophil and lactoferrin-to-neutrophil ratios were significantly lower than in the controls and the stage 2 CKD patients. (4) Our multivariate linear regression analyses showed that age, pulse pressure, mean arterial pressure, PTH, and FGF-23 were independently associated with ba-PWV values. Conclusions: Circulating FGF-23 and angiogenin concentrations gradually increased as CKD advanced, whereas neutrophil activation markers were significantly lower in the stage 3-4 CKD/HD patients than in the controls and stage 2 CKD patients. FGF-23 was weakly associated with ba-PWV values in patients with CKD/HD and no previous cardiovascular disease.