Top

Clinical Rheumatology

Published in:

01-12-2020 | Original Article

Associations of serum iron and ferritin with hyperuricemia and serum uric acid

Authors: Yilun Wang, Zidan Yang, Jing Wu, Dongxing Xie, Tuo Yang, Hui Li, Yilin Xiong

Published in: Clinical Rheumatology | Issue 12/2020

Abstract

Objectives

To assess the serum iron and ferritin levels in relation to the prevalence of hyperuricemia (HU) and the serum uric acid (SUA) level.

Methods

Serum iron and ferritin concentrations were detected by Ferene method and chemiluminescence method, respectively. SUA level was detected by uricase-PAP method. HU was defined as SUA ≥ 416 μmol/L for male and ≥ 357 μmol/L for female. Multivariable-adjusted logistic regressions were constructed to investigate the associations between serum iron/ferritin levels and prevalence of HU. Pearson correlation analysis and multivariable linear regression were performed to examine the correlations between serum iron/ferritin levels and SUA level.

Results

A total of 2824 subjects (mean age 52.2 ± 7.2) were included. The overall prevalence of HU was 17.3%. Compared with the lowest quartile, the multivariable-adjusted odds ratios (OR) and its 95% confidence interval (CI) of HU were 1.33 (95%CI 0.97–1.82), 1.17 (95%CI 0.85–1.60), and 1.56 (95%CI 1.14–2.13) in the second, third, and fourth quartiles of serum iron, respectively (P for trend = 0.012), and were 1.29 (95%CI 0.89–1.88) in the second, 2.13 (95%CI 1.47–3.07) in the third, and 2.25 (95%CI 1.54–3.29) in the fourth quartile of serum ferritin (P for trend < 0.001). Pearson correlation coefficient indicated a weak positive correlation between serum iron (r = 0.2, P < 0.001) and ferritin (r = 0.3, P < 0.001) levels and SUA. Such positive correlations were further confirmed by multiple linear regression (serum iron: standardized β = 0.059, P < 0.001; serum ferritin: standardized β = 0.061, P = 0.001).

Conclusions

Both serum iron and ferritin showed a positive correlation with the prevalence of HU, and a weak positive correlation with SUA level.

Key Points

• Subjects with higher levels of serum iron or ferritin had higher prevalence of HU.

• There was a weak positive correlation between serum iron/ferritin levels and SUA level.

Waring WS, Webb DJ, Maxwell SR (2001) Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. J Cardiovasc Pharmacol 38(3):365–371. https://doi.org/10.1097/00005344-200109000-00005CrossRefPubMed

Hou H, Xu X, Sun F, Zhang X, Dong H, Wang L, Ge S, An K, Sun Q, Li Y, Cao W, Song M, Hu S, Xing W, Wang W, Li D, Wang Y (2019) Hyperuricemia is associated with immunoglobulin G N-glycosylation: a community-based study of glycan biomarkers. OMICS 23:660–667. https://doi.org/10.1089/omi.2019.0004CrossRefPubMed

Arrebola JP, Ramos JJ, Bartolome M, Esteban M, Huetos O, Canas AI, Lopez-Herranz A, Calvo E, Perez-Gomez B, Castano A, Bioambient. Es (2019) Associations of multiple exposures to persistent toxic substances with the risk of hyperuricemia and subclinical uric acid levels in BIOAMBIENT.ES study. Environ Int 123:512–521. https://doi.org/10.1016/j.envint.2018.12.030CrossRefPubMed

Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK (2019) Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: the National Health and Nutrition Examination Survey 2007-2016. Arthritis Rheum 71:991–999. https://doi.org/10.1002/art.40807CrossRef

Trifiro G, Morabito P, Cavagna L, Ferrajolo C, Pecchioli S, Simonetti M, Bianchini E, Medea G, Cricelli C, Caputi AP, Mazzaglia G (2013) Epidemiology of gout and hyperuricaemia in Italy during the years 2005-2009: a nationwide population-based study. Ann Rheum Dis 72(5):694–700. https://doi.org/10.1136/annrheumdis-2011-201254CrossRefPubMed

Liu R, Han C, Wu D, Xia X, Gu J, Guan H, Shan Z, Teng W (2015) Prevalence of Hyperuricemia and gout in mainland China from 2000 to 2014: a systematic review and meta-analysis. Biomed Res Int 2015:762820–762812. https://doi.org/10.1155/2015/762820CrossRefPubMedPubMedCentral

Billa G, Dargad R, Mehta A (2018) Prevalence of Hyperuricemia in Indian subjects attending Hyperuricemia screening programs-a retrospective study. J Assoc Physicians India 66(4):43–46PubMed

Zhu Y, Pandya BJ, Choi HK (2011) Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum 63(10):3136–3141. https://doi.org/10.1002/art.30520CrossRefPubMed

Chen S, Du H, Wang Y, Xu L (1998) The epidemiology study of hyperuricemia and gout in a community population of Huangpu District in Shanghai. Chin Med J 111(3):228–230PubMed

10.

Huang H, Huang B, Li Y, Huang Y, Li J, Yao H, Jing X, Chen J, Wang J (2014) Uric acid and risk of heart failure: a systematic review and meta-analysis. Eur J Heart Fail 16(1):15–24. https://doi.org/10.1093/eurjhf/hft132CrossRefPubMed

11.

Zhu Y, Pandya BJ, Choi HK (2012) Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am J Med 125(7):679–687.e671. https://doi.org/10.1016/j.amjmed.2011.09.033CrossRefPubMed

12.

Ford ES, Li C, Cook S, Choi HK (2007) Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents. Circulation 115(19):2526–2532. https://doi.org/10.1161/CIRCULATIONAHA.106.657627CrossRefPubMed

13.

Wang H, Zhang H, Sun L, Guo W (2018) Roles of hyperuricemia in metabolic syndrome and cardiac-kidney-vascular system diseases. Am J Transl Res 10(9):2749–2763PubMedPubMedCentral

14.

Fernández-Real JM, Manco M (2014) Effects of iron overload on chronic metabolic diseases. Lancet Diabetes Endocrinol 2(6):513–526. https://doi.org/10.1016/s2213-8587(13)70174-8CrossRefPubMed

15.

Schmidt PJ (2015) Regulation of Iron metabolism by Hepcidin under conditions of inflammation. J Biol Chem 290(31):18975–18983. https://doi.org/10.1074/jbc.R115.650150CrossRefPubMedPubMedCentral

16.

Flais J, Bardou-Jacquet E, Deugnier Y, Coiffier G, Perdriger A, Chales G, Ropert M, Loreal O, Guggenbuhl P (2017) Hyperferritinemia increases the risk of hyperuricemia in HFE-hereditary hemochromatosis. Joint Bone Spine 84(3):293–297. https://doi.org/10.1016/j.jbspin.2016.05.020CrossRefPubMed

17.

Haap M, Fritsche A, Mensing HJ, Haring HU, Stumvoll M (2003) Association of high serum ferritin concentration with glucose intolerance and insulin resistance in healthy people. Ann Intern Med 139(10):869–871. https://doi.org/10.7326/0003-4819-139-10-200311180-00029CrossRefPubMed

18.

Dasgupta S, Dasgupta A, Mukhopadhayay T, Bhattacharya S, Swaika B, Banarjee U, Chakrabarty P (2013) Serum uric acid: an early indicator of oxidative stress in beta thalassemia population. Mymensingh Med J 22(3):567–573PubMed

19.

Budzyn M, Iskra M, Krasinski Z, Dzieciuchowicz L, Kasprzak M, Gryszczynska B (2011) Serum iron concentration and plasma oxidant-antioxidant balance in patients with chronic venous insufficency. Med Sci Monit 17(12):CR719–CR727. https://doi.org/10.12659/msm.882132CrossRefPubMedPubMedCentral

20.

Zeng C, Wei J, Li H, Yang T, Zhang FJ, Pan D, Xiao YB, Yang TB, Lei GH (2015) Relationship between serum magnesium concentration and radiographic knee osteoarthritis. J Rheumatol 42(7):1231–1236. https://doi.org/10.3899/jrheum.141414CrossRefPubMed

21.

Zeng C, Wang YL, Wei J, Yang T, Li H, Xie DX, Li YS, Lei GH (2015) Association between low serum magnesium concentration and hyperuricemia. Magnes Res 28(2):56–63. https://doi.org/10.1684/mrh.2015.0384CrossRefPubMed

22.

Zeng C, Wei J, Terkeltaub R, Yang T, Choi HK, Wang YL, Xie DX, Hunter DJ, Zhang Y, Li H, Cui Y, Li LJ, Lei GH (2017) Dose-response relationship between lower serum magnesium level and higher prevalence of knee chondrocalcinosis. Arthritis Res Ther 19(1):236. https://doi.org/10.1186/s13075-017-1450-6CrossRefPubMedPubMedCentral

23.

Zhang YN, Xu C, Xu L, Yu C, Miao M, Xie J, Li Y (2014) High serum ferritin levels increase the risk of hyperuricemia: a cross-sectional and longitudinal study. Ann Nutr Metab 64(1):6–12. https://doi.org/10.1159/000358337CrossRefPubMed

24.

Zhang W, Doherty M, Pascual E, Bardin T, Barskova V, Conaghan P, Gerster J, Jacobs J, Leeb B, Liote F, McCarthy G, Netter P, Nuki G, Perez-Ruiz F, Pignone A, Pimentao J, Punzi L, Roddy E, Uhlig T, Zimmermann-Gorska I, Therapeutics ESCfICSI (2006) EULAR evidence based recommendations for gout. Part I: diagnosis. Report of a task force of the standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 65(10):1301–1311. https://doi.org/10.1136/ard.2006.055251CrossRefPubMedPubMedCentral

25.

Veronese N, Stubbs B, Trevisan C, Bolzetta F, De Rui M, Maggi S, Sartori L, Musacchio E, Zambon S, Perissinotto E, Noale M, Crepaldi G, Manzato E, Sergi G (2017) Results of an observational cohort study of Hyperuricemia as a predictor of poor physical performance in the elderly. Arthritis Care Res 69(8):1238–1244. https://doi.org/10.1002/acr.23118CrossRef

26.

Levey AS, Stevens LA, Schmid CH, Zhang Y, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612. https://doi.org/10.7326/0003-4819-150-9-200905050-00006CrossRefPubMedPubMedCentral

27.

Ghio AJ, Ford ES, Kennedy TP, Hoidal JR (2005) The association between serum ferritin and uric acid in humans. Free Radic Res 39(3):337–342. https://doi.org/10.1080/10715760400026088CrossRefPubMed

28.

Kuo CC, Weaver V, Fadrowski JJ, Lin YS, Guallar E, Navas-Acien A (2015) Arsenic exposure, hyperuricemia, and gout in US adults. Environ Int 76:32–40. https://doi.org/10.1016/j.envint.2014.11.015CrossRefPubMed

29.

Hunnicutt J, He K, Xun P (2014) Dietary iron intake and body iron stores are associated with risk of coronary heart disease in a meta-analysis of prospective cohort studies. J Nutr 144(3):359–366. https://doi.org/10.3945/jn.113.185124CrossRefPubMedPubMedCentral

30.

van der A D, Grobbee DE, Roest M, Marx JJ, Voorbij HA, van der Schouw YT (2005) Serum ferritin is a risk factor for stroke in postmenopausal women. Stroke 36(8):1637–1641. https://doi.org/10.1161/01.STR.0000173172.82880.72CrossRef

31.

Mainous AG 3rd, Knoll ME, Everett CJ, Matheson EM, Hulihan MM, Grant AM (2011) Uric acid as a potential cue to screen for iron overload. J Am Board Fam Med 24(4):415–421. https://doi.org/10.3122/jabfm.2011.04.110015CrossRefPubMed

32.

Li X, He T, Yu K, Lu Q, Alkasir R, Guo G, Xue Y (2018) Markers of Iron status are associated with risk of Hyperuricemia among Chinese adults: nationwide population-based study. Nutrients 10(2):E191. https://doi.org/10.3390/nu10020191CrossRefPubMed

33.

Chen C, Lü J-M, Yao Q (2016) Hyperuricemia-related diseases and xanthine oxidoreductase (XOR) inhibitors: an overview. Med Sci Monit 22:2501–2512. https://doi.org/10.12659/msm.899852CrossRefPubMedPubMedCentral

34.

Martelin E, Lapatto R, Raivio KO (2002) Regulation of xanthine oxidoreductase by intracellular iron. Am J Phys Cell Phys 283(6):C1722–C1728. https://doi.org/10.1152/ajpcell.00280.2002CrossRef

35.

Zeng QY, Chen R, Darmawan J, Xiao ZY, Chen SB, Wigley R, Le Chen S, Zhang NZ (2008) Rheumatic diseases in China. Arthritis Res Ther 10(1):R17. https://doi.org/10.1186/ar2368CrossRefPubMedPubMedCentral

36.

Kelley MK, Amy NK (1984) Effect of molybdenum-deficient and low iron diets on xanthine oxidase activity and iron status in rats. J Nutr 114(9):1652–1659. https://doi.org/10.1093/jn/114.9.1652CrossRefPubMed

37.

Ghio AJ, Kennedy TP, Stonehuerner J, Carter JD, Skinner KA, Parks DA, Hoidal JR (2002) Iron regulates xanthine oxidase activity in the lung. Am J Phys Lung Cell Mol Phys 283(3):L563–L572. https://doi.org/10.1152/ajplung.00413.2000CrossRef

38.

Huang J, Jones D, Luo B, Sanderson M, Soto J, Abel ED, Cooksey RC, McClain DA (2011) Iron overload and diabetes risk: a shift from glucose to fatty acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis. Diabetes 60(1):80–87. https://doi.org/10.2337/db10-0593CrossRefPubMed

39.

Valenti L, Fracanzani AL, Dongiovanni P, Bugianesi E, Marchesini G, Manzini P, Vanni E, Fargion S (2007) Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case-control study. Am J Gastroenterol 102(6):1251–1258. https://doi.org/10.1111/j.1572-0241.2007.01192.xCrossRefPubMed

40.

Quinones Galvan A, Natali A, Baldi S, Frascerra S, Sanna G, Ciociaro D, Ferrannini E (1995) Effect of insulin on uric acid excretion in humans. Am J Phys 268(1 Pt 1):E1–E5. https://doi.org/10.1152/ajpendo.1995.268.1.E1CrossRef

41.

Modan M, Halkin H, Karasik A, Lusky A (1987) Elevated serum uric acid--a facet of hyperinsulinaemia. Diabetologia 30(9):713–718. https://doi.org/10.1007/bf00296994CrossRefPubMed

Title: Associations of serum iron and ferritin with hyperuricemia and serum uric acid
Authors: Yilun Wang
Zidan Yang
Jing Wu
Dongxing Xie
Tuo Yang
Hui Li
Yilin Xiong
Publication date: 01-12-2020
Publisher: Springer International Publishing
Published in: Clinical Rheumatology / Issue 12/2020
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-020-05164-7

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Associations of serum iron and ferritin with hyperuricemia and serum uric acid

Abstract

Objectives

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2020

Investigating correlation between self-reported clinical manifestation and synovial fluid and blood levels of Dickkopf-1 and sclerostin in patients with primary knee osteoarthritis

Comparison of persistence rates between allopurinol and febuxostat as first-line urate-lowering therapy in patients with gout: an 8-year retrospective cohort study

Ultrasonographic features of acute Charcot neuroarthropathy of the foot: a pilot study

Human touch in digital education—a solution

Cachexia in patients with rheumatoid arthritis: a cohort study

Anxiety and depression in adult-onset Still’s disease patients and associations with health-related quality of life

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page