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 m2 without pathologic, urine [proteinuria], blood [electrolyte], and imaging abnormalities; n = 22); (2) CKD stage 2 (eGFR 60–89 mL/min/1.73 m2; n = 17); (3) CKD stage 3 (eGFR 30–59 mL/min/1.73 m2; n = 22); (4) CKD stage 4 (eGFR 15–30 mL/min/1.73 m2; 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 log10(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.

Angiogenin—A Proposed Biomarker for Cardiovascular Disease—Is Not Associated With Long-Term Survival in Patients With Peripheral Artery Disease

“…3 Since patients with diabetes mellitus often qualify for the term metabolic syndrome, this finding might actually be based on the observed association of the patient's waist-to-hip ratio and angiogenin in the current study. Angiogenin levels are increased in advanced chronic kidney disease 14 and hemodialysis patients. 32 The present study adds that angiogenin levels are linked to eGFR levels (CKD-EPI formula) in moderate kidney disease.…”

“…Angiogenin levels are increased in advanced chronic kidney disease 14 and hemodialysis patients. 32 The present study adds that angiogenin levels are linked to eGFR levels (CKD-EPI formula) in moderate kidney disease.…”

“… 3 In chronic kidney disease, angiogenin has been demonstrated to gradually increase with kidney disease progression assessed by chronic kidney disease stage in a small patient cohort. 14 Experimental in vitro hypoxemia models in periodontal fibroblasts increased expression of angiogenin. 15 Apart from angiogenesis, angiogenin has been shown to induce nitric oxide synthase activity.…”

Evidence of retinal arteriolar narrowing in patients with autosomal-dominant polycystic kidney disease

“…PC-1 and PC-2 assemble in the plasma membrane to regulate the calcium (Ca 2+ ) entry mechanism. The other biological functions of polycystins (PCs) are still under investigation [4].The presence of kidney cysts is a characteristic feature in ADPKD patients and is necessary to establish the diagnosis [5]. Cystic pathology in the course of ADPKD is believed to be the result of abnormal cell proliferation and deregulated apoptosis [6].…”

“…The presence of kidney cysts is a characteristic feature in ADPKD patients and is necessary to establish the diagnosis [5]. Cystic pathology in the course of ADPKD is believed to be the result of abnormal cell proliferation and deregulated apoptosis [6].…”