|Year : 2019 | Volume
| Issue : 3 | Page : 320-327
The evaluation of preoperative and postoperative fetuin-A levels in patients with primary hyperparathyroidism
M Keskin1, C Culha2, NE Gulcelik2, LI Al3, M Senes4, Y Aral2
1 Department of Endocrinology and Metabolism, Kecioren Training and Research Hospital, Ankara, Turkey
2 Department of Endocrinology and Metabolism, Ankara Training and Research Hospital, Ankara, Turkey
3 Department of Internal Medicine, Kecioren Training and Research Hospital, Ankara, Turkey
4 Department of Internal Medicine, Ankara Training and Research Hospital, Ankara, Turkey
|Date of Acceptance||13-Nov-2018|
|Date of Web Publication||6-Mar-2019|
Dr. M Keskin
Department of Endocrinology and Metabolism, Kecioren Training and Research Hospital, Ankara
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objectives: Our objective was to evaluate preoperative and postoperative serum fetuin-A levels in female patients with primary hyperparathyroidism (PHPT) and search for the relationship with parathyroid hormone (PTH) and vitamin D (25OHD). Although a role for fetuin-A is suggested in regulating bone mineralization, its function has not been completely defined. Materials and Methods: In this cross-sectional study, 43 female patients with PHPT and 30 healthy women were recruited as the control group. We evaluated 73 women because we had only women patients with PHPT. Of the 43 patients, 10 symptomatic and 23 asymptomatic patients were surgically treated, whereas 10 patients were not operated. In all 43 patients, 25OHD, PTH, fetuin-A levels, and bone mineral densitometry were evaluated. The biochemical parameters of 33 operated patients were reevaluated at the postoperative sixth week. Results: Fetuin-A levels of the patients with PHPT were significantly higher than that in the controls (56.6 ± 13.8 vs. 42.6 ± 20.7 ng/mL; P = 0.010). Fetuin-A levels of the operated patients were higher than nonoperated group. Furthermore, serum fetuin-A levels of the nonoperated patients were not different from those of controls. After parathyroidectomy, fetuin-A (41.5 ± 25.2 vs. 56.4 ± 13.7 ng/mL; P = 0.003), PTH [80.0 (51.5–137.5) vs. 211.0 (151.5–278.5) pg/mL; P < 0.001], and calcium (9.2 ± 0.7 vs. 10.7 ± 0.8 mg/dL; P < 0.001) values were found to be decreased significantly. Conclusion: In this study, fetuin-A levels of patients with PHPT were higher than those of the controls and significantly decreased after parathyroidectomy compared with the preoperative levels. Fetuin-A levels could be a beneficial marker to determine the changes in bone metabolism of the patients with PHPT and to detect the patients suitable for surgery.
Keywords: Bone marker, fetuin-A, parathyroidectomy, primary hyperparathyroidism
|How to cite this article:|
Keskin M, Culha C, Gulcelik N E, Al L I, Senes M, Aral Y. The evaluation of preoperative and postoperative fetuin-A levels in patients with primary hyperparathyroidism. Niger J Clin Pract 2019;22:320-7
|How to cite this URL:|
Keskin M, Culha C, Gulcelik N E, Al L I, Senes M, Aral Y. The evaluation of preoperative and postoperative fetuin-A levels in patients with primary hyperparathyroidism. Niger J Clin Pract [serial online] 2019 [cited 2019 Mar 22];22:320-7. Available from: http://www.njcponline.com/text.asp?2019/22/3/320/253448
| Introduction|| |
Fetuin-A has a glycoprotein structure and is a noncollagen protein, which was first described in 1944 by Pedersen. It is one of the major systemic inhibitors of pathological mineralization. Fetuin-A is a negative acute phase reactant, which is synthesized by the liver in adults.,, Lower fetuin-A levels are found in inflammation and atherosclerosis, and it has been reported that low fetuin-A levels are associated with vascular calcification., The abundance of fetuin in bone suggests that this glycoprotein may have a role in bone formation or remodeling., Many of the studies about fetuin-A have been conducted in patients with chronic kidney disease (CKD). The association of fetuin-A deficiency with increased cardiovascular disease and mortality was noted in both hemodialysis (HD) and peritoneal dialysis patients., It is also reported that serum fetuin-A levels are reduced in patients undergoing dialysis. It is shown that the knockout mice for fetuin gene had a low mineralized bone, cartilage calcification, and extraskeletal calcifications., It is reported that serum fetuin-A levels are associated with bone mineral density (BMD), and bone resorption markers. It is demonstrated that DBA2-fetuin−/− mice had 10-fold high PTH levels, a marked osteopenia, and calcium and phosphate concentrations within normal range. Osteopenia was a result of kidney calcification and secondary hyperparathyroidism.
It is conceivable that fetuin-A levels may be related to high calcium levels in patients with primary hyperparathyroidism (PHPT). The role of fetuin-A associated with bone metabolism is not yet clearly identified. We were not able to find any previous studies published related to fetuin-A levels of patients with PHPT. We studied the preoperative and postoperative changes in fetuin-A levels of patients with PHPT and its relations with parathyroid hormone (PTH) and vitamin D (25OHD) and aimed to investigate its importance in bone metabolism. The relations of fetuin-A with bone density and calcium levels were also researched.
| Materials and Methods|| |
The study was approved by the Regional Committee for Medical and Health Research Ethics in our hospital (reference number: 2014/34161). A written informed consent was obtained from each patient. The study was conducted in accordance with the principles of the Declaration of Helsinki. In all, 43 female patients diagnosed as PHPT and 30 healthy females forming the control group were included in the study between 2014 and 2015. A total of 33 patients, composed of 10 symptomatic patients and 23 asymptomatic patients diagnosed with operation indication according to the clinical guidelines, were surgically treated. Ten patients were not operated. The biochemical parameters of the operated and nonoperated patients, including fetuin-A, were compared preoperatively and postoperatively and assessed in relation to possible changes.
Exclusion criteria were as follows: having malignancy, hormone replacement treatment or osteoporosis treatment, diabetes mellitus, chronic kidney disease, chronic liver disease, steroid treatment, active infections, collagen tissue diseases, and inflammatory diseases. Fetuin-A, PTH, 25OHD, alkaline phosphatase (ALP), fasting blood glucose, calcium, phosphate, lipid profile, renal function tests, high sensitivity C-reactive protein (hs-CRP), osteocalcin, bone-specific alkaline phosphatase (BALP), and BMD were evaluated for all 43 female patients. Vitamin D treatment was given to patients who have low vitamin D levels in the preoperative period.
The values were compared with those of 30 healthy female controls and 10 nonoperated patients. The biochemical parameters of 33 operated patients were reevaluated at the postoperative sixth week.
All blood samples were taken in the morning after at least 12 h of fasting. The serum was separated and stored in aliquots at −80°C for later analysis of fetuin-A levels. Fetuin-A was measured using a human fetuin-A enzyme-linked immunosorbent assay kit (Epitope Diagnostics, San Diego, CA, USA). Intra- and interassay coefficients of variation were 2.4%–4.7% and 9.5%–9.9%, respectively.
Whether the distributions of continuous variables were normal or not was determined by Kolmogorov–Smirnov test. Levene's test was used for the evaluation of homogeneity of variances. Data were shown as mean ± standard deviation or median (25th–75th) percentiles, where applicable. While the mean differences among groups were analyzed by one-way analysis of variance (ANOVA), Kruskal–Wallis test was applied for comparisons in which continuous variables did not meet parametrical test assumptions. When the P values from one-way ANOVA or Kruskal–Wallis test statistics were statistically significant, post hoc Tukey's HSD or Conover's multiple comparison test was used to know which group differs from which others. Whether the differences between pre- and postop clinical measurements were statistically significant or not were evaluated by paired samples t-test or Wilcoxon sign-rank test, where appropriate. Degrees of association between continuous variables were evaluated by Spearman's rank correlation analyses.
Multiple linear regression analysis was applied for determining the best predictor(s) which affect on fetuin-A measurements after adjustment for all possible confounding factors. Any variable whose univariable test had a P value <0.10 was accepted as a candidate for the multivariable model along with all variables of known clinical importance. Coefficient of regression, 95% confidence interval, and t-statistic for each independent variable were also calculated.
Data analysis was performed using IBM SPSS Statistics version 17.0 software (IBM Corporation, Armonk, NY, USA). A P value less than 0.05 was considered statistically significant.
| Results|| |
Demographical data of the patients (operated and nonoperated) and of the controls are given in [Table 1]. The significant difference was not found for age among the groups (P = 0.192). The levels of fetuin-A (56.6 ± 13.8 vs. 42.6 ± 20.7 ng/mL; P = 0.010) [Figure 1], PTH [211.0 (151.5–323.5) vs. 56.5 (42.4–65.2) pg/mL; P < 0.001], calcium (10.7 ± 0.8 vs. 9.3 ± 0.4 mg/dL; P < 0.001), osteocalcin [12.3 (4.4–18.4) vs. 5.5 (4.0–7.4) ng/dL; P = 0.002], ALP (115.4 ± 56.9 vs. 75.8 ± 17.0 U/L; P < 0.001), BALP (58.4 ± 18.1 vs. 50.4 ± 15.8%; P = 0.030), and hs-CRP [3.8 (2.2–6.6) vs. 1.6 (1.0–3.8) mg/dL; P < 0.05] were significantly higher in operated patients than in the control group. As expected, BMD values and phosphate (P) levels were significantly lower in the patient group. Preoperative BMD T scores of our study patients were approximately in L1–L4: −2.0 ± 1.2 g/cm2, femur neck: −1.0 ± 1.3 g/cm2, and when this value was compared with the control group, a significant decrease was evident (P < 0.001, P = 0.003, respectively).
|Figure 1: Fetuin-A levels of the operated and nonoperated patients and of the controls|
Click here to view
There was no statistically significant difference between groups in terms of median 25OHD [18.4 (9.7–26.3) vs. 17.7 (12.4–21.0) ng/mL; P = 0.644] levels. When the operated patients were compared with the nonoperated ones preoperatively, it was found that fetuin-A (56.6 ± 13.8 vs. 42.9 ± 18.2 ng/mL; P = 0.01), PTH [211.0 (151.5–323.5) vs. 133.0 (109.5–186.7) pg/mL; P < 0.001], calcium (10.7 ± 0.8 vs. 9.4 ± 0.5 mg/dL; P < 0.001), ALP (115.4 ± 56.9 vs. 74.7 ± 18.8 U/L; P < 0.001), BALP (58.4 ± 18.1 vs. 51.2 ± 12.5%; P = 0.03), and hs-CRP [3.8 (2.2–6.6) vs. 2.0 (1.0–4.5) mg/dL; P < 0.05] values were higher, whereas phosphate (2.6 ± 0.6 vs. 3.4 ± 0.5 mg/dL; P < 0.001) and L1–L4 (−2.0 ± 1.2 vs. −0.5 ± 1.4 g/cm2; P < 0.001) values were lower in the operated patients.
In addition, when we compared the nonoperated patients with the controls, we found that PTH [133.0 (109.5–186.7) vs. 56.5 (42.4–65.2) pg/mL; P < 0.001] and osteocalcin [10.0 (6.8–12.6) vs. 5.5 (4.0–7.4) ng/dL; P = 0.002] levels were higher in the nonoperated patients. Fetuin-A levels of the nonoperated patients were not different from those of the controls. Moreover, calcium, phosphate, 25OHD, and hs-CRP levels of the nonoperated patients were similar to the controls.
When the results of correlation analyses between fetuin-A and other demographical and laboratory measurements within all subjects (n = 73) were examined, a statistically significant positive correlation between calcium and fetuin-A (r = 0.263; P = 0.025) [Table 2] and [Figure 2] was found, whereas a statistically significant negative correlation was present between phosphate and fetuin-A levels (r = −0.309; P = 0.008) [Table 2] and [Figure 3]. No significant correlation was detected among the remaining variables and fetuin-A.
|Table 2: The results of correlation analyses between fetuin-A and other demographical and laboratory measurements within all subjects (n=73)|
Click here to view
|Figure 2: Fetuin-A levels positively correlated with the levels of calcium|
Click here to view
|Figure 3: Fetuin-A levels negatively correlated with the levels of phosphate|
Click here to view
When the results of multiple linear regression analysis (n = 73) were evaluated, “being operated” was found to be a significant predictor to estimate the changes in fetuin-A measurements, as an independent risk factor. An increase in fetuin-A levels of operated patients was observed when the effects of other factors were held constant (13.867 ng/mL an increase, 95% confidence interval: 0.678–27.055) (P = 0.040) [Table 3].
When the pre- and postoperative clinical measurements of the operated cases were examined [Table 4], it was found that fetuin-A (41.5 ± 25.2 vs. 56.4 ± 13.7 ng/mL; P = 0.003) levels significantly decreased in the operated patient group, in the postoperative sixth week. Also, PTH, calcium, BALP, and hs-CRP levels significantly decreased in the postoperative period (P < 0.001, P < 0.001, P = 0.041, and P < 0.001, respectively). A statistically significant increase was found in postoperative osteocalcin and phosphate levels (P = 0.029 and P < 0.001, respectively).
No significant difference was observed between fetuin-A levels of the operated patients and the controls in the postoperative period (41.5 ± 25.2 vs. 42.6 ± 20.7 ng/mL; P = 0.342). Also, postoperative 25OHD [19.1 (6.0–54) vs. 18.7 (5.0–43) ng/mL; P = 0.136] levels were not different from the preoperative 25OHD levels.
When evaluating the results of correlation analyses between preoperative laboratory measurements and the difference in fetuin-A in the operated cases, a statistically significant correlation was not detected [Table 5].
|Table 5: The results of correlation analyses between baseline (preop) laboratory measurements and difference in fetuin-A within operated cases (n = 33)|
Click here to view
In the operated cases, the evaluation of the results of correlation analyses between the differences in fetuin-A and other laboratory measurements revealed a statistically significant correlation [Table 6]. As a result, a significant correlation was not detected either between fetuin-A and PTH or fetuin-A and 25 (OHD).
|Table 6: The results of correlation analyses between the differences in fetuin-A and other laboratory measurements within operated cases (n = 33)|
Click here to view
| Discussion|| |
In this study, fetuin-A levels of patients with PHPT were significantly higher than that in the controls. Furthermore, fetuin-A levels of the operated patients owing to PHPT were significantly decreased compared with the preoperative levels during the postoperative control. A positive significant relation was found between fetuin-A and calcium levels, whereas a negative significant relation was found between fetuin-A and phosphate levels. No correlation was determined between fetuin-A levels and PTH values of the patients, and no significant relation was also detected between BMD and fetuin-A levels.
It has been shown that PHPT is associated with reduced BMD mainly at sites rich in cortical bone., Preoperative BMD T scores of our study patients were significantly lower than of the controls.
Low fetuin-A, poor nutrition (low albumin), and chronic inflammation are important risk factors for vascular calcification in patients with CKD., Treatment strategies to reduce vascular calcifications have focused on hyperphosphatemia, hypercalcemia, high calcium–phosphorus product, hyperparathyroidism, smoking, dyslipidemia, or hypertension. Hamano et al. reported that levels of fetuin-A were decreased by centrifugation in HD patients but not in normal control subjects. They demonstrated that ELISA or nephelometry measures different fractions of fetuin-A. This could explain why most studies that used nephelometry yielded positive results, whereas most of the negative studies of serum fetuin-A used ELISAs. They found that the serum of patients on HD contained fetuin–mineral complex and was composed of fetuin-A, fibrinogen, fibronectin-1, and calcium. We also used the ELISA method. This situation could have affected our results. Therefore, fetuin-A levels might have been detected to be lower than we expected.
In the study by Ix JH et al., serum fetuin-A was found to be significantly associated with BMD for older women (mean age 74 years), and they reported that higher BMD values were associated with higher serum fetuin-A levels in older women. Chailurkit et al. found that circulating fetuin-A is related to bone density (L2–L4 BMD) and bone resorption markers (C-terminal cross-linked telopeptide of type 1 collagen, serum CTX). In our study, no significant relation was determined between fetuin-A and BMD levels in our female patient group (mean age 53 years). Wu et al. showed that serum fetuin-A level is closely correlated with osteoporosis and it may serve as a predictor of osteoporosis. Fetuin-A is known to stabilize calcium phosphate precursors as colloid. It has been reported that fetuin-A prevents calcification by buffering excess extracellular mineral. Fetuin-A precludes uncontrolled mineralization that may occur under pathological conditions. Therefore, fetuin-A may be important in preventing calcification in the context of elevated concentrations of mineral ions. It is well-known that fetuin-A levels decrease in patients undergoing dialysis. We found higher fetuin-A levels in patients with PHPT than controls. We observed a decrease in fetuin-A levels after parathyroidectomy. Wang et al. showed that serum fetuin-A levels increase after parathyroidectomy in uremic hyperparathyroidism. This discrepancy may be important. High serum calcium and ionized phosphorus levels can reduce fetuin-A levels in patients undergoing dialysis. Reduction in ionized calcium and phosphorus after parathyroidectomy and decreased consumption of fetuin-A (in response to high calcium X ionized phosphorus product) have been found to be partially responsible for the increase in fetuin-A level in HD patients with secondary hyperparathyroidism. We could expect an association between high serum calcium and serum fetuin-A level in patients with PHPT. It is demonstrated that calcium X ionized phosphorus product (Ca X P product) in uremic patients is inversely correlated with serum fetuin-A level. Haddad et al. reported no significant correlation between fetuin-A and Ca X P product determined in HD patients. Therefore, it is expected to lower fetuin-A values in patients with PHPT than in controls because of the high Ca X P product. But we found higher fetuin-A levels in patients with PHPT than the controls. Wang et al. found that the degree of increase in fetuin-A levels was positively correlated with the degree of reduction in ionized calcium 30 days after parathyroidectomy. Separately, this correlation was not significant 14 days after parathyroidectomy. In our study, we evaluated fetuin-A levels and its relations with other biochemical parameters 45 days (6 week) after parathyroidectomy. The delayed increase in fetuin-A may be due to the time required for the de novo synthesis of fetuin-A from hepatocytes. The difference in our results may partially be related to this. On the other hand, Haddad et al. reported that there was no significant relation between PTH and fetuin-A levels, which is compatible with our results. High fetuin-A levels in patients with PHPT may be found to prevent calcification in the context of elevated concentrations of mineral ions, as compensatory. Cardiovascular risk is also increased in patients with PHPT. Obesity, hypertension, insulin resistance, and hyperlipidemia are more prevalent in patients with severe PHPT. It is also shown that high fetuin-A levels are associated with insulin resistance, metabolic syndrome, fatty liver disease, and atherogenic lipid profile., High fetuin-A levels may be protective for cardiovascular events by functioning to keep calcium and phosphorus solubilized in serum, thus preventing hydroxyapatite deposition in vessel walls. Indeed, in patients with end-stage renal disease, low fetuin-A concentrations were associated with higher rates of cardiovascular and all-cause mortality. Considering that the main effect of fetuin-A is to inhibit Ca-P segregation, the reason for high fetuin-A levels before treatment could be intracellular calcium increase.
It is known that patients with tertiary hyperparathyroidism have excessive high PTH and normal/high calcium levels and chronic renal failure. Thus, fetuin-A levels may be expected to be related to calcium levels. In our study, fetuin-A levels were found to be positively correlated with the levels of calcium and negatively correlated with the levels of phosphate.
Mohamed et al. reported a positive correlation between fetuin-A and calcium, and a negative relationship between fetuin-A and PTH in patients with CKD with type 2 diabetes. Chailurkit et al. found a relationship between serum fetuin-A and serum calcium level in older women.
A negative significant correlation was found between fetuin-A and hs-CRP on patients undergoing HD., Ix et al. and Hennige et al. reported a positive correlation between fetuin-A and hs-CRP., Marechal et al. could not find any correlation. In our study, a positive correlation was determined between fetuin-A level and hs-CRP of the patients. Wang et al. showed that fetuin-A is classified as a negative acute phase protein (APP) during infection or other inflammatory illness (in acute inflammation, fetuin-A seems to act as a negative APP and an anti-inflammatory modulator) and a positive APP in injury. Separately, fetuin-A levels are elevated in patients with cerebral ischemic injury (stroke). Increased hs-CRP together with fetuin-A in our patients may be due to a chronic low-grade inflammation. Haddad et al. reported no significant correlation was found between serum fetuin-A and PTH. On the contrary, we found that these two parameters significantly decreased postoperatively, but we could not determine a significant correlation between them.
Vitamin D treatment has given different results on fetuin-A levels in patients undergoing HD.,, Norenstedt et al. reported that the additive effect of vitamin D supplementation lowers the PTH level after parathyroidectomy in patients with PHPT. In our study, vitamin D treatment was given to patients who had low vitamin D levels in the preoperative period. Fetuin-A measurement method and vitamin D treatment could affect fetuin-A levels. Fetuin-A levels might have increased as a compensatory in the preoperative period in our patients.
Furthermore, our study had some limitations. First, some correlations may have not been identified due to the small sample size. The identification of the relation of fetuin-A with PTH and BMD may require a longer time of disease history. The third limitation may be the requirement of following the patients for a longer time in the postoperative period. Larger multicenter studies with longer follow-up intervals are needed to confirm these findings.
| Conclusion|| |
Patients with PHPT had higher fetuin-A levels than control subjects, which decreased significantly after parathyroidectomy. Thus, fetuin-A levels could be a beneficial marker to determine the changes in bone metabolism of patients with PHPT and to detect the patients suitable for surgery.
Financial support and sponsorship
Conflict of interest
There are no conflicts of interest.
| References|| |
Jahnen-Dechent W, Heiss A, Schafer C, Ketteler M. Fetuin-A regulation of calcified matrix metabolism. Circ Res 2011;108:1494-509.
Marechal C. Schlieper G, Nguyen P, Krüger T, Coche E, Robert A, et al
. Serum fetuin-A levels are associated with vascular calcifications and predict cardiovascular events in renal transplant recipients. Clin J Am Soc Nephrol 2011;6:974-85.
Wang H, Sama AE. Anti-inflammatory role of fetuin-A in injury and infection. Curr Mol Med 2012;12:625-33.
Binkert C, Demetriou M, Sukhu B, Szweras M, Tenenbaum HC, Dennis JW. Regulation of osteogenesis by fetuin. J Biol Chem 1999;274:28514-520.
Brylka L, Jahnen-Dechent W. The role of fetuin-A in physiological and pathological mineralization. Calcif Tissue Int 2013;93:355-64.
Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P, et al
. Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 2005;20:1676-85.
Mori K, Emoto M, Inaba M. Fetuin A: A multifunctional protein. Recent Pat Endocr Metab Immune Drug Discov 2011;5:124-46.
Haddad M, Tajbakhsh R, Farajollahi M, Qorbani M, Besharat S, Joshaghani HR. Association of serum fetuin-A and biochemical parameters in hemodialysis patients. Saudi J Kidney Dis Transpl 2014;25:769-73.
] [Full text]
Masi L. Epidemiology of osteoporosis. Clinical Cases Miner Bone Metab 2008;5:11-3.
Jahnen-Dechent W, Schinke T, Trindl A, Müler-Estrel W, Sablitzky F, Kaiser S, et al
. Cloning and targeted deletion of the mouse fetuin gene. J Biol Chem 1997;272:31496-503.
Ix JH, Wassel CL, Bauer DC, Toroian D, Tylavsky FA, Cauley JA, et al
. Fetuin-A and BMD in older persons: The Health Aging and Body Composition (Health ABC) Study. J Bone Miner Res 2009;24:514-21.
Chailurkit L. Kruavit A, Rajatanavin R, Ongphiphadhanakul B. The relationship of fetuin-A and lactoferrin with bone mass in elderly women. Osteoporos Int 2011;22:2159-64.
Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, et al
. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003;112:357-66.
Moosgaard B, Christensen SE, Vestergaard P, Heickendorff L, Christiansen P, Mosekilde L. Vitamin D metabolites and skeletal consequences in primary hyperparathyroidism. Clin Endocrinol 2008;68:707-15.
Hamano T, Matsui I, Mikami S, Tomida K, Fujii N, Imai E, et al
. Fetuin-mineral complex reflects extraosseous calcification stress in CKD. J Am Soc Nephrol 2010;21:1998-2007.
Román-García P, Rodríguez-García M, Cabezas-Rodríguez I, López-Ongil S, Díaz-López B, Cannata-Andía JB. Vascular calcification in patients with chronic kidney disease: types, clinical impact and pathogenesis. Med Princ Pract 2011;20:203-12.
Wu Q, Xiao DM, Fan WF, Ye XW, Niu JY, Gu Y. Effect of serum fibroblast growth factor-23, matrix Gla protein and fetuin-A in predicting osteoporosis in maintenance hemodialysis patients. Ther Apher Dial 2014;18:427-33.
Reynolds JL, Skepper JN, Mcnair R, Kasama T, Gupta K, Weissberg PL, et al
. Multifunctional roles for serum protein fetuin-A in inhibition of human vascular smooth muscle cell calcification. J Am Soc Nephrol 2005;16:2920-30.
Wang CC, Hsu YJ, Wu CC, Yang SS, Chen GS, Lin SH, et al
. Serum fetuin-A levels increased following parathyroidectomy in uremic hyperparathyroidism. Clin Nephrol 2012;77:89-96.
Pertosa G, Simone S, Ciccone M, Porreca S, Zaza G, Dalfino G, et al
. Serum fetuin-A in hemodialysis: A link between derangement of calcium-phosphorus homeostasis and progression of atherosclerosis? Am J Kidney Dis 2009;53:467-74.
Luboshitzky R, Chertok-Schaham Y, Lavi I, Ishay A. Cardiovascular risk factors in primary hyperparathyroidism. J Endocrinol Invest 2009;32:317-21.
Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA. Association between human fetuin-A and the metabolic syndrome: Data from the Heart and Soul Study. Circulation 2006;113:1760-67.
Dabrowska AM, Tarach JS, W Duma B, Duma D. Feuin-A (AHSG) and its usefulness in clinical practise. Review of the literature. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2015;159:352-9.
Mohamed AK, Abdallah AM, Hassan MA, Mohammed NA, Kamel SA. Association of fetuin-A level with vascular disease in hemodialysis patients with or without type II diabetes mellitus. Egypt J Intern Med 2013;25:218-24. [Full text]
Hennige AM, Staiger H, Wicke C, Machicao F, Fritsche A, Häring HU, et al
. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One 2008;3:e1765, 1-9.
Massart A, Debelle FD, Racape J, Gervy C, Husson C, Dhaene M, et al
. Biochemical parameters after cholecalciferol repletion in hemodialysis: Results from the Vitadial Randomized Trial. Am J Kidney Dis 2014;64:696-705.
Manenti L, Vaglio A, Pasquali S. Increased fetuin-A levels following treatment with a Vitamin D analog. Letter to The Editor. Kidney Int 2010;78:1187.
Price PA, Williamson MK, Nguyen TM, Than TN. Serum levels of the fetuin-mineral complex correlate with artery calcification in the rat. J Biol Chem 2004;279:1594-1600.
Norenstedt S, Pernow Y, Brismar K, Saaf M, Ekip A, Granath F, et al
. Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind Study. Eur J Endocrinol 2013;169:795-804.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]