fetuin-A Levels Research Articles

Fetuin-A decrease induced by a low-protein diet enhances vascular calcification in uremic rats with hyperphosphatemia.

Although dietary phosphate restriction is important for treating hyperphosphatemia in patients with chronic kidney disease, it remains unclear whether a low-protein diet (LPD), which contains low phosphate, has beneficial effects on malnutrition, inflammation, and vascular calcification. The effects of LPD on inflammation, malnutrition, and vascular calcification were therefore assessed in rats. Rats were fed a normal diet or diets containing 0.3% adenine and low/normal protein and low/high phosphate. After 6 wk, serum and urinary biochemical parameters, systemic inflammation, and vascular calcification were examined. The protective effect of fetuin-A and albumin were assessed in cultured vascular smooth muscle cells. Rats fed the diet containing 0.3% adenine developed severe azotemia. LPD in rats fed high phosphate induced malnutrition (decreases in body weight, food intake, serum albumin and fetuin-A levels, and urinary creatinine excretion) and systemic inflammation (increases in serum tumor necrosis factor-α and urinary oxidative stress marker). LPD decreased the serum fetuin-A level and fetuin-A synthesis in the liver and increased serum calcium-phosphate precipitates. A high-phosphate diet increased aortic calcium content, which was enhanced by LPD. Reduced fetal calf serum in the medium of cultured vascular smooth muscle cells enhanced phosphate-induced formation of calcium-phosphate precipitates in the media and calcification of vascular smooth muscle cells, both of which were prevented by fetuin-A administration. Our results suggest that phosphate restriction by restricting dietary protein promotes vascular calcification by lowering the systemic fetuin-A level and increasing serum calcium-phosphate precipitates and induces inflammation and malnutrition in uremic rats fed a high-phosphate diet.

Association of Serum Fetuin-A Levels with Allograft Outcome in Renal Transplant Recipients.

To determine serum fetuin-A pattern after renal transplantation and its association with graft outcome. In 41 renal transplant recipients, serum pretransplant fetuin-A levels and serum fetuin-A concentrations on days 7 and 30 after transplantation were measured using the enzyme-linked immunosorbent as­say (ELISA) method. Also, the association between serum fetuin-A levels with clinical and laboratory parameters was evaluated. A significant decrease in serum fetuin-A levels was noted in the first week after transplantation (P < .001). Subsequently, it started to increase and surpass pretransplant values during the first month (P < .001). Pretransplant fetuin-A levels did not differ among patients with different diethylenetriamine pentaacetic acid (DTPA) results. In addition, serum fetuin-A levels did not significantly correlate with metabolic parameters. In this prospective study there was no increase in serum fetuin-A levels during the first month and pretransplant fetuin-A levels are not predictive for allograft outcome in renal transplant recipients.

Correlation of Clinical Effects with Levels of Fetuin-A, FGF-23 and intact Parathormone in Peritoneal Dialysis Patients

Objective: We aimed to demonstrate the clinical effects of fetuin–A, fibroblast growth factor-23 and intact parathormone on the risk factors for metabolic disorders and cardiovascular diseases in peritoneal dialysis patients. Materials and Method: A total of 41 patients who had undergone peritoneal dialysis therapy were included in the study. The study groups were divided into two groups according to intact parathormone levels, which were below and above 72 pg/mL. Serum levels of fetuin-A, fibroblast growth factor-23, biochemical parameters and carotid intima media thickness were measured in both the groups. Echocardiography was performed. Result: Mean fetuin-A levels were not found to be lower and no statistically significant difference was determined between the two groups. No correlations were demonstrated between the levels of fetuin-A and the risk factors for cardiovascular diseases and biochemical parameters. Mean fibroblast growth factor-23 levels were significantly higher. No statistically significant difference was observed in the levels of fibroblast growth factor-23 between the groups. No correlations were determined between the levels of fibroblast growth factor-23 and the risk factors for cardiovascular diseases and biochemical parameters, except LDL-cholesterol. A significant negative correlation was found between the levels of fibroblast growth factor-23 and LDL-cholesterol. Conclusion: No unfavorable effects of serum fetuin-A and fibroblast growth factor-23 levels on cardiovascular morbidity were found. Dialysis adequacy, duration of dialysis, the use of treatment and different mechanisms may be the cause of changes in clinical effects and levels of fetuin-A and fibroblast growth factor-23 in dialysis patients.

Matrix γ-carboxyglutamate protein and Fetuin-A, in wet type age-related macular degeneration.

To evaluate the high sensitivity C-reactive protein (hsCRP), Fetuin-A and matrix γ-carboxyglutamate protein (MGP) as the main factors for vascular calcification and inflammation in serum of patients with advanced age-related macular degeneration (ARMD) in comparison to healthy controls. The subjects were 40 patients with choroidal neovascularization (CNV) having a mean age of 70.9±9.1y and a matched group of 49 apparently healthy control subjects. The ARMD was diagnosed using a slit-lamp with superfield lens, fundus photography and fluorescein angiography. Measurement of hsCRP was done by nephelometry method. Levels of Fetuin-A and MGP were measured by enzyme-linked immunosorbent assay (ELISA) technique. hsCRP [0.45(0.07-2.63) mg/L vs 0.25(0.03-1.2) mg/L, P=0.02)] and Fetuin-A levels (50.27±5.04 vs 44.99±10.28 ng/mL, P=0.009) were higher in the patients than in the control groups. We could not find significant difference in MGP level between two groups (P=0.08). There was not a significant correlation between MGP with Fetuin-A and hsCRP among the patients (P=0.7, P=0.9 respectively). A significant negative correlation of hsCRP with Fetuin-A was observed in both case and control groups (P=0.004, r=-0.33 and P=0.001, r=-0.54, respectively). Although our study shows that serum hsCRP and Fetuin-A is increased in CNV patients as well as negatively correlated with both study groups, their direct role on pathogenesis of ARMD required future studies.

Serum fetuin-A levels and abdominal aortic calcification in healthy men — The STRAMBO study

Vascular calcification results from an imbalance between increased extracellular levels of calcium and phosphate, reduced solubility, and low levels of calcification inhibitors in blood or the vascular wall. Fetuin-A is a major circulating calcification inhibitor. Rodent models of fetuin-A deficit indicate its calcification inhibiting potential. Clinical studies suggest its role as a biomarker in vascular disease. This cross-sectional study was performed in a cohort of 974 men aged ≥40years (average 68years) consisting of men holding health insurance cover with Mutuelle des Travailleurs de la Région Lyonnaise. Abdominal aortic calcification (AAC) was assessed semi-quantitatively on lateral dual energy X-ray absorptiometry (DXA) spine scans. Serum fetuin-A was measured by an immunoassay. After adjustment for confounders (age, lifestyle, body composition, health status, treatment, glomerular filtration rate [GFR], hormones, and cytokines), prevalence of severe AAC (AAC score>4) decreased with increasing fetuin-A levels (OR=0.68 per SD increase, 95% CI: 0.54–0.84, p<0.001). After adjustment for confounders, low fetuin-A and hypertension were each associated with higher odds of AAC>4. Coexistence of low serum fetuin-A levels and heavy smoking, elevated fibroblast growth factor 23 levels or low serum dickkopf-1 levels were associated with higher odds of AAC>4. Similar results were obtained for 789 men with GFR>60mL/min/1.73m2. Similar results were obtained when severe AAC was defined as AAC score >3 or AAC>5.Thus, lower serum fetuin-A levels are associated with severe AAC, suggesting that poor calcification inhibitory potential contributes to vascular calcification, independently of renal impairment.

Indoxyl sulfate suppresses hepatic fetuin-A expression via the aryl hydrocarbon receptor in HepG2 cells.

Fetuin-A is a liver-derived circulating protein that has potent calcification-inhibitory activity. Uraemic patients exhibit decreased serum fetuin-A levels, increased vascular calcification and elevated cardiovascular mortality. Because the mechanisms for fetuin-A deficiency are unknown, we hypothesized that some uraemic toxins suppressed hepatic fetuin-A production, which resulted in accelerated vascular calcification and poor outcome. Among these potential candidates, indoxyl sulfate (IS) has highly toxic properties. We examined the direct effects of IS on hepatic fetuin-A expression using the human hepatoma HepG2 cell line. IS, but not p-cresyl sulfate, suppressed the mRNA and protein expression of fetuin-A in a dose- and time-dependent manner. As reported previously, IS stimulated p38 MAPK phosphorylation and reactive oxygen species (ROS) production, although the knockdown of p38 and inhibition of ROS generation had no effect on IS-induced fetuin-A suppression. Then, because IS is a potent endogenous ligand of the aryl hydrocarbon receptor (AhR), we assessed whether IS suppresses fetuin-A production via AhR. The knockdown of AhR prevented IS-induced fetuin-A suppression. However, some attention should be paid to no effect of IS on fetuin-A expression in mouse and human primary cultured hepatocytes. These findings suggest that IS could suppress hepatic fetuin-A expression by activating AhR, suggesting a relationship between uraemia and fetuin-A deficiency.

Fibroblast Growth Factor 21 and Fetuin-A in Obese Adolescents With and Without Type 2 Diabetes.

Hepatokines such as fetuin-A or fibroblast growth factor 21 (FGF21) are reasonable candidates affecting the pathophysiology of type 2 diabetes mellitus (T2DM). However, studies in humans at the onset of disease are scarce. The objective of the study was to compare FGF21 and fetuin-A levels between adolescents with and without T2DM. This was a cross-sectional comparison of adolescents with and without T2DM. The study was conducted at diabetes and obesity treatment centers. Seventy-four predominantly Caucasian adolescents with T2DM aged 12-18 years and 74 body mass index (BMI)-, age-, and gender-matched controls participated in the study. There were no interventions. FGF21 and fetuin-A and their correlation to age, BMI, glycated hemoglobin, blood pressure, lipids, adiponectin, and leptin were measured. Adolescents with T2DM showed significant higher FGF21 serum concentrations compared with obese controls without T2DM [median 277 pg/mL (interquartile range [IQR] 161-586) vs 200 pg/mL (IQR 116-323), respectively, P = .009] and higher fetuin-A serum concentrations (median 0.30 g/L (IQR 0.27-0.33) vs 0.28 g/L (IQR 0.25-0.30), respectively, P = .005). In a multiple linear regression analysis, fetuin-A was positively associated with glycated hemoglobin [β-coefficient 0.005 (95% confidence interval ± 0.004), P = .013], negatively with adiponectin (β-coefficient -0.004 (95% confidence interval ±0.002, P = .006) but not with BMI, age, gender, ethnicity, or leptin. FGF21 was not associated with any parameter in multiple linear regression analysis. Increased FGF21 serum levels in obese adolescents with T2DM compared with obese adolescents without T2DM suggest a FGF21-resistant state in T2DM because FGF21 improves insulin sensitivity. The increase of fetuin-A levels in obese adolescents with T2DM supports the hypothesis that fetuin-A is involved in the pathogenesis of T2DM because this hepatokine leads to insulin resistance.

Fetuin-A is related to infarct size, left ventricular function and remodelling after acute STEMI

ObjectiveTo investigate the relationship between plasma fetuin-A, an anti-inflammatory glycoprotein which might be involved in myocardial healing after acute infarction, and infarct size, left ventricular (LV) function and dimensions as...

Association Between Cardiac Valvular Calcification and Serum Fetuin-A Levels in Renal Transplant Recipients

BackgroundThe presence of cardiac valvular calcification in patients with chronic kidney disease has become important. We aimed to evaluate the prevalence of cardiac valvular calcification and its association with serum Fetuin-A levels in kidney transplant recipients. MethodsThe cardiac valvular calcification was assessed by echocardiography in 89 kidney transplant recipients. Serum Fetuin-A levels were measured by use of the enzyme-linked immunosorbent assay method. ResultsPatients were divided into 3 groups: patients without cardiac valvular calcification (n = 14), patients with aortic valve calcification (n = 51), and patients with both aortic and mitral valve calcification (n = 24). Aortic calcification area and number of aortic calcifications were significantly increased in the group with aortic and mitral calcification group compared with the other two groups. These two parameters were also significantly increased in patients with cardiac valvular calcification compared with patients without cardiac valvular calcification. Serum Fetuin-A levels were significantly increased in patients with aortic valve calcification compared with the other two groups, whereas there were no significant differences between these two groups. Serum Fetuin-A levels were positively correlated with blood urea nitrogen level (r = .241, P = .025) and serum creatinine level (r = .262, P = .014), whereas it was negatively correlated with serum phosphorus level (r = −.409, P < .001). ConclusionsSerum Fetuin-A levels can be taken into consideration for the assessment of patients in terms of cardiac valvular calcification, depending on the relationship between serum Fetuin-A levels and cardiac valvular calcification during follow-up after kidney transplantation.

Living kidney donation does not adversely affect serum calcification propensity and markers of vascular stiffness.

Living kidney donors (LKDs) experience a decline in glomerular filtration rate (GFR) after donation. Calcification propensity (T50 ) can be determined by a blood test predicting all-cause mortality in patients with chronic kidney disease. We studied the impact of kidney donation on T50 and markers of arterial stiffness. We analyzed T50 prospectively before and 1year after kidney donation in 21 LKDs along with fetuin-A, mineral metabolism markers, kidney length, pulse wave velocity (PWV), augmentation index (AI), and renal resistive index (RRI) as markers of arterial stiffness. We studied the impact of kidney donation on these parameters. LKDs were 54±10years old and had a GFR of 101±18ml/min/1.73m(2) before donation, decreasing to 67±8ml/min/1.73m(2) after donation (P<0.001). Despite this, T50 improved after donation (290±53 to 312±38min, P=0.049). This change was inversely related to plasma phosphate (P=0.03), which declined after donation (P=0.002). Fetuin-A levels increased after donation (P=0.01). Upon donation, the length of the remaining kidney increased (P<0.001) while PWV, AI, and RRI remained unchanged. Calcification propensity was not adversely affected by kidney donation. This indicates that T50 is independent from GFR in LKDs and that kidney donation does neither worsen calcification propensity nor markers of vascular stiffness at 1year.

Diabetes Associated Markers After Bariatric Surgery: Fetuin-A, but Not Matrix Metalloproteinase-7, Is Reduced.

Recent studies showed that fetuin-A and matrix metalloproteinase-7 (MMP-7) are type 2 diabetes mellitus (T2DM)-associated markers. Bariatric surgery not only reduces body weight but also improves T2DM. This study aimed to investigate the changes of fetuin-A and MMP-7 in obese subjects with and without T2DM after bariatric surgery. We enrolled 130 obese subjects that received bariatric surgery, including 41 Roux-en-Y gastric bypass (RYGB), 67 mini-gastric bypass (MGB), and 22 sleeve gastrectomy (SG) patients. Forty-three patients suffered from T2DM prior to surgery. The fasting serum fetuin-A and MMP-7 levels were measured before and 1 year after surgery. Only five of 43 patients remained diabetic after surgery. Preoperative T2DM patients had higher fetuin-A and MMP-7 levels than non-T2DM subjects. RYGB, MGB, and SG all decreased the fetuin-A levels 1 year after the operation. The MMP-7 levels were not changed after RYGB, MGB, or SG. In multivariate analyses, the preoperative fetuin-A was significantly related to the diastolic blood pressure (DBP) and glycosylated hemoglobin (HbA1c), while the postoperative fetuin-A was independently related to the waist-to-hip ratio and HbA1c. Moreover, the preoperative MMP-7 level was significantly related to age, DBP, aspartate transaminase, alanine transaminase, and gamma-glutamyl transferase (rGT), while the postoperative MMP-7 level was independently related to age and rGT. The fetuin-A and MMP-7 levels are both higher in obese T2DM than non-T2DM subjects. The level of fetuin-A is reduced after RYGB, MGB, and SG, but the level of MMP-7 remains unchanged.

Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome

ObjectiveAdipose Tissue (AT) dysregulation contributes to the pro-inflammatory state and insulin resistance of Metabolic Syndrome (MetS). We examined AT secretion of the hepatokine, Fetuin-A, LBP, sCD14 and HMGB-1, and toll-like receptor 2 and 4 protein levels in MetS and controls. Design and methodsSecreted levels of Fetuin-A, LBP, HMGB-1 and sCD14 and TLR2 and TLR4 protein in AT of controls and MetS patients were assayed. Also mRNA and protein for Fetuin-A, LBP, sCD14 and HMGB-1 were studied in subcutaneous fat depot of mice and during adipocyte differentiation. ResultsSecretion of Fetuin-A, LBP and HMGB-1 from AT were significantly increased in MetS (n = 28) compared to controls (n = 25), even after adjustment for adiposity. There were no significant differences in sCD14. Both LBP and Fetuin-A correlated significantly with HOMA-IR and increased significantly with increasing features of MetS. There was a significant increase in AT TLR2 and TLR4 protein in MetS compared to controls. Expression of Fetuin-A and LBP were significantly higher in subcutaneous white adipose tissue of HFD fed mice as well as in ob/ob mice compared to C57BL6/J control mice (n = 6 per group). Additionally mRNA and protein levels of FetA, LBP and HMGB-1 increased during differentiation of 3T3-L1 adipocytes. ConclusionsWe make the novel observation of increased secretion of Fetuin A, LBP and HMGB-1 from AT and hypothesize that these engage TLRs in AT and other tissues contributing to the pro-inflammatory state and insulin resistance of MetS.

Association of plasma fetuin-A levels and peripheral vascular disease in type 2 diabetic patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

TLR2/4 dependent and independent effects of the hepatokine fetuin-A in islets

Background and Aim: The nonalcoholic fatty liver displays an altered secretion of hepatokines. Notably, increased plasma levels of the hepatokine fetuin-A strongly predicts the incidence of type-2 diabetes in humans. Fetuin-A inhibits insulin receptor signaling and augments inflammation. Fatty acid-induced activation of TLR4 in adipocytes has been found to depend on fetuin-A. The present study examines effects of fetuin-A on pancreatic islet cell function.

Serum Visfatin, Fetuin-A, and Pentraxin 3 Levels in Patients With Psoriasis and Their Relation to Disease Severity.

Psoriasis is a chronic immune-mediated inflammatory skin disease associated with increase of some pro-inflammatory mediators. We wanted to investigate whether there is a relationship between psoriasis and visfatin, fetuin-A and pentraxin 3 (PTX3)-pro-inflammatory mediators implicated in the development of insulin resistance (IR), metabolic syndrome, and atherosclerosis. Visfatin, fetuin-A, and PTX3 concentrations were measured in 45 patients with plaque-type psoriasis and 45 healthy controls using enzyme-linked immunosorbent assay (ELISA). Serum levels of visfatin, fetuin-A, and PTX3 in patients with psoriasis were found to be higher than in healthy controls (P = 0.002, P = 0.009, P < 0.001, respectively). Psoriasis area and severity index (PASI) score correlated significantly with visfatin and fetuin-A levels (P = 0.011, P = 0.040, respectively). There was a significant positive correlation between visfatin and fetuin-A (P < 0.001). PTX3 levels were correlated positively with homeostasis model assessment (HOMA-IR), insulin, triglyceride (TG), and very low density lipoprotein cholesterol (VLDL; P = 0.009, P = 0.007, P = 0.023, P = 0.024, respectively). Increased serum visfatin, fetuin-A, and PTX3 levels, and the presence of positive correlation between visfatin, fetuin-A, and PASI score, probably reflect the inflammatory state and IR seen in psoriasis.

Associations of Fibroblast Growth Factor 23 and Fetuin-A With Coronary Plaque Burden and Plaque Composition in Young Adults

ObjectiveThe total burden of subclinical coronary artery disease (CAD) is significant among young adults. Serum fibroblast growth factor 23 (FGF-23) and fetuin-A are established predictors of morbidity and mortality because...

Both diabetes and fetuin-A are independently associated with increased risk of arterial stiffness

BackgroundArterial stiffness is a functional assessment of vascular damage caused by cardiovascular disease (CVD) risk factors. Fetuin-A is associated with subclinical CVD and incident or fatal CVD, with some modification of its effect occurring with the presence of diabetes. We investigated the impact of different glycemic statuses and serum fetuin-A levels on arterial stiffness. MethodsA total of 312 age- and sex-matched subjects with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and newly diagnosed diabetes (NDD) were recruited. Serum fetuin-A levels were measured, and arterial stiffness was assessed by brachial-ankle pulse-wave velocity (baPWV). ResultsWe found that the mean values of baPWV were 1533±338, 1518±353, 1589±307, and 1690±414cm/s, and fetuin-A levels were 298±69, 313±67, 330±86, and 342±93μg/ml, in subjects with NGT, IFG, IGT, and NDD, respectively (both p<0.001, test for trend). NDD subjects had significantly higher baPWV and fetuin-A levels than those with NGT. Multiple linear regression analysis showed that age, fetuin-A, diabetes, hypertension, and hypertriglyceridemia are independently associated factors of baPWV after adjusting for cardiometabolic risk factors, HOMA-IR, and adiponectin. ConclusionBoth diabetes and fetuin-A levels are independently associated with arterial stiffness. Fetuin-A may further aggravate increased arterial stiffness in diabetes.

P0981 : Adaptation of hepatic mitochondrial function in obese humans with or without non-alcoholic steatohepatitis

Background and Aims: Patients with non-alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth. We aimed to test the hypothesis that endotoxaemia is associated with fatty liver in the general population and to study dietary factors associated with endotoxaemia. Methods: Community adult subjects were randomly selected from the Hong Kong Government’s census database and underwent proton-magnetic resonance spectroscopy and transient elastography to assess hepatic steatosis and fibrosis, respectively. Intrahepatic triglyceride content (IHTG) of 5% was the cutoff to define fatty liver. Endotoxaemia was assessed using the Limulus Amebocyte Lysate, lipopolysaccharide-binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays. Dietary pattern was recorded by a 7-day food-frequency questionnaire. Results: 920 subjects were included (42% male, age 48±11, 23% body mass index ≥25kg/m and 5% diabetes). 263 (29%) had fatty liver; 60 (7%) had raised serum cytokeratin-18 fragment level (CK-18) suggestive of NASH; 27 of 887 (3%) subjects with reliable liver stiffness measurement had advanced fibrosis or cirrhosis. Compared with those without fatty liver, subjects with fatty liver had higher LBP (13.4±3.2mg/ml vs 11.4±2.7mg/ml; P < 0.001) and EndoCab IgG (228±247 GMU/ml vs 188±137 GMU/ml; P = 0.013) levels. Endotoxin markers also correlated positively with aminotransferases, IHTG, CK-18, insulin resistance and dyslipidaemia. Endotoxaemia was not associated with increased liver stiffness. Fetuin-A, the ligand linking fatty acid and Toll-like receptor 4, correlated with IHTG, insulin resistance and dyslipidaemia but did not have consistent association with endotoxaemia markers. Although total energy consumption and individual macronutrients were not associated with endotoxaemia, current drinkers (median alcohol consumption 20g/week [interquartile range 10–70 g]) had lower endotoxin, EndoCab IgG and fetuin-A levels than non-drinkers. Conclusions: Endotoxaemia is associated with fatty liver and possibly NASH in the general population. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of fatty liver and NASH in modest drinkers in previous observational studies. This study was supported by a grant from the Health and Medical Research Fund sponsored by the Hong Kong SAR Government [Ref CUHK-11120621]. P0981 ADAPTATION OF HEPATIC MITOCHONDRIAL FUNCTION IN OBESE HUMANS WITH OR WITHOUT NON-ALCOHOLIC STEATOHEPATITIS C. Koliaki, J. Szendroedi, K. Kaul, T. Jelenik, P. Nowotny, F. Jankowiak, C. Herder, M. Carstensen, M. Krausch, W. Trudo Knoefel, M. Schlensak, M. Roden. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Dusseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Dusseldorf, Germany; Department of Endocrinology and Diabetology, Heinrich Heine University, Dusseldorf, Germany; Institute of Pathology, Heinrich Heine University, Dusseldorf, Germany; Department of General, Visceral and Pediatric Surgery, Heinrich Heine University, Dusseldorf, Germany; General Surgery Department, St. Martinus Hospital, Dusseldorf, Germany, Dusseldorf, Germany E-mail: ckoliaki@yahoo.com

Urine Fetuin-A is a biomarker of autosomal dominant polycystic kidney disease progression.

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by numerous fluid-filled cysts that frequently result in end-stage renal disease. While promising treatment options are in advanced clinical development, early diagnosis and follow-up remain a major challenge. We therefore evaluated the diagnostic value of Fetuin-A as a new biomarker of ADPKD in human urine.ResultsWe found that renal Fetuin-A levels are upregulated in both Pkd1 and Bicc1 mouse models of ADPKD. Measurement by ELISA revealed that urinary Fetuin-A levels were significantly higher in 66 ADPKD patients (17.5 ± 12.5 μg/mmol creatinine) compared to 17 healthy volunteers (8.5 ± 3.8 μg/mmol creatinine) or 50 control patients with renal diseases of other causes (6.2 ± 2.9 μg/mmol creatinine). Receiver operating characteristics (ROC) analysis of urinary Fetuin-A levels for ADPKD rendered an optimum cut-off value of 12.2 μg/mmol creatinine, corresponding to 94% of sensitivity and 60% of specificity (area under the curve 0.74 ; p = 0.0019). Furthermore, urinary Fetuin-A levels in ADPKD patients correlated with the degree of renal insufficiency and showed a significant increase in patients with preserved renal function followed for two years.ConclusionsOur findings establish urinary Fetuin-A as a sensitive biomarker of the progression of ADPKD. Further studies are required to examine the pathogenic mechanisms of elevated renal and urinary Fetuin-A in ADPKD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0463-7) contains supplementary material, which is available to authorized users.

Relationship of vitamin D status and bone mass according to vitamin D-binding protein genotypes.

BackgroundVitamin D-binding protein (DBP) may alter the biological activity of total 25-hydroxyvitamin D [25(OH)D]; this could influence on the effects of vitamin D in relation to bone mineral density (BMD) and fractures. Emerging data suggest that fetuin-A may be involved in bone metabolism. We aimed to investigate the influence of DBP gene polymorphism on the relationship of vitamin D status and fetuin-A levels to BMD and bone markers.MethodsThis cross-sectional study was part of a health survey of employees of the Electricity Generating Authority of Thailand (1,734 healthy subjects, 72% male). Fasting blood samples were assayed for 25(OH)D, fetuin-A, N-terminal propeptides of type 1 procollagen (P1NP), C-terminal cross-linking telopeptides of type I collagen (CTx-I), and DBP rs2282679 genotypes. L1–L4 lumbar spine and femoral BMD were measured using dual-energy X-ray absorptiometry.ResultsThe DBP rs2282679 genotype distribution conformed to the Hardy–Weinberg equilibrium. There were no correlations between 25(OH)D levels and BMD and bone markers. But a trend of positive correlation was observed for the DBP genotypes with total hip BMD, and for the interaction between 25(OH)D and DBP genotypes with BMD at all femoral sites. We further analyzed data according to DBP genotypes. Only in subjects with the AA (common) genotype, 25(OH)D levels were positively related to BMD and bone markers, while fetuin-A was negatively related to total hip BMD, independently of age, gender and BMI.ConclusionsThe interaction between vitamin D status, as measured by circulating 25(OH)D and DBP rs2282679 genotypes, modified the association between 25(OH)D and BMD and bone markers. Differences in DBP genotypes additionally influenced the correlation of fetuin-A levels with femoral BMD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12937-015-0016-1) contains supplementary material, which is available to authorized users.