Abstract
The relationship between exposure to certain metals and the risk of hyperuricemia (HUA) has biological plausibility, yet prior studies have presented inconsistent findings. We aim to clarify the relationship between exposure to certain metals and HUA using a systematic review and meta-analysis approach. We searched the Web of Science, Embase, MEDLINE, Pubmed, Corchrane and China National Knowledge Infrastructure databases from inception through December, 2021 in order to identify studies that assessed the relationships between metals and the risk of HUA. Data were pooled by random-effects models and expressed as pooled odds ratios (OR) and 95% confidence intervals (CIs). The risk of bias was assessed using a tool from Agency for Healthcare Research and Quality (AHRQ). Twenty eligible articles (nineteen cross-sectional studies and one cohort) were included in our analysis, involving 63,283 participants in total. The studies showed that arsenic (pooled OR = 1.702, 95% CI: 1.44, 2.011; n = 6, I2 = 29.5%), calcium (pooled OR = 1.765, 1.111, 2.804; 4, 82.3%), cadmium (pooled OR = 1.199,1.020, 1.410; 11, 38.5%) and lead (pooled OR = 1.564,1.205, 2.030; 11, 72.9%) exposure were, all linked to an increased risk of HUA. Exposure to molybdenum (pooled OR = 0.804, 0.724, 0.975, 3, 0%) was linked to a decreased risk of HUA, however. Exposure to arsenic, calcium, cadmium and lead is associated with an increased risk of HUA. Molybdenum exposure was associated with a decreased prevalence of HUA; however, aluminum, cobalt, copper, iron, magnesium, manganese, mercury, selenium, thallium and zinc are not associated with HUA risk. Further experimental studies are warranted to decipher the mechanisms by which exposure to the above metals affect HUA risk. The findings reinforced the importance of metals in the HUA risk, and provided a reference for legislation to prevent HUA and protect people's health.
Similar content being viewed by others
Data availability
All data generated or analyzed during this study can be found at the 3 databases (PubMed, EMBASE, Corchrane and China National Knowledge Infrastructure).
References
Li Y, Shen Z, Zhu B et al (2021) Demographic, regional and temporal trends of hyperuricemia epidemics in mainland China from 2000 to 2019: a systematic review and meta-analysis. Glob Health Action 14(1):1874652. https://doi.org/10.1080/16549716.2021.1874652
Kim Y, Kang J, Kim GT (2018) Prevalence of hyperuricemia and its associated factors in the general Korean population: an analysis of a population-based nationally representative sample. Clinical Rheumatol 37(9):2529–2538. https://doi.org/10.1007/s10067-018-4130-2
Zuo T, Liu X, Jiang L et al (2016) Hyperuricemia and coronary heart disease mortality: a meta-analysis of prospective cohort studies. BMC Cardiovasc Disord 16(1):207. https://doi.org/10.1186/s12872-016-0379-z
Kuwabara M, Hisatome I, Niwa K, Hara S et al (2018) Uric acid is a strong risk marker for developing hypertension from prehypertension: a 5-year Japanese cohort study. Hypertension 71(1):78–86. https://doi.org/10.1161/HYPERTENSIONAHA.117.10370
Kielstein JT, Pontremoli R, Burnier M (2020) Management of hyperuricemia in patients with chronic kidney disease: a focus on renal protection. Curr Hypertens Rep 22(12):102. https://doi.org/10.1007/s11906-020-01116-3
Park DY, Kim YS, Ryu SH, Jin YS (2019) The association between sedentary behavior, physical activity and hyperuricemia. Vasc Health Risk Manag 15:291–299. https://doi.org/10.2147/VHRM.S200278
Gao Y, Cui LF, Sun YY et al (2021) Adherence to the dietary approaches to stop hypertension diet and hyperuricemia: a cross-sectional study. Arthritis Care Res (Hoboken) 73(4):603–611. https://doi.org/10.1002/acr.24150
Juraschek SP, Yokose C, McCormick N et al (2021) Effects of dietary patterns on serum urate: results from a randomized trial of the effects of diet on hypertension. Arthritis Rheumatol 73(6):1014–1020. https://doi.org/10.1002/art.41614
Li L, Zhang Y, Zeng C (2020) Update on the epidemiology, genetics, and therapeutic options of hyperuricemia. Am J Transl Res 12(7):3167–3181
Garza-Lombó C, Posadas Y, Quintanar L et al (2018) Neurotoxicity linked to dysfunctional metal ion homeostasis and xenobiotic metal exposure: redox signaling and oxidative stress. Antioxid Redox Signal 28(18):1669–1703. https://doi.org/10.1089/ars.2017.7272
Roberts EA, Sarkar B (2014) Metalloproteomics: focus on metabolic issues relating to metals. Curr Opin Clin Nutr Metab Care 17(5):425–430. https://doi.org/10.1097/MCO.0000000000000085
Zoroddu MA, Aaseth J, Crisponi G et al (2019) The essential metals for humans: a brief overview. J Inorg Biochem 195:120–129. https://doi.org/10.1016/j.jinorgbio.2019.03.013
Sun H, Wang N, Chen C et al (2017) Cadmium exposure and its association with serum uric acid and hyperuricemia. Sci Rep 7(1):550. https://doi.org/10.1038/s41598-017-00661-3
Park J, Kim Y (2021) Associations of blood heavy metals with uric acid in the Korean general population: analysis of data from the 2016–2017 Korean national health and nutrition examination Survey. Biol Trace Elem Res 199(1):102–112. https://doi.org/10.1007/s12011-020-02152-5
Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis OF Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–2012. https://doi.org/10.1001/jama.283.15.2008
Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097
Higgins JP, Thompson SG, Deeks JJ et al (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. https://doi.org/10.1136/bmj.327.7414.557
Cao J, Zhang J, Zhang Y et al (2020) Plasma magnesium and the risk of new-onset hyperuricaemia in hypertensive patients. Br J Nutr:1–8. https://doi.org/10.1017/S0007114520001099
Dai H, Huang Z, Deng Q et al (2015) The Effects of lead exposure on serum uric acid and hyperuricemia in Chinese adults: a cross-sectional study. Int J Environ Res Public Health 12(8):9672–9682. https://doi.org/10.3390/ijerph120809672
Gao E (2020) Effect of urinary metal concentration and food intake pattern on hyperuricemia in urban elderly. Dissertation, Huazhong University of Science and Technology
He X (2020) Association of plasma multiple metals with hyperuricemia risk in medical examination population. Dissertation, Jinan University
Jiang T, Xie D, Wu J et al (2020) Association between serum copper levels and prevalence of hyperuricemia: a cross-sectional study. Sci Rep 10(1):8687. https://doi.org/10.1038/s41598-020-65639-0
Jung W, Kim Y, Lihm H, Kang J (2019) Associations between blood lead, cadmium, and mercury levels with hyperuricemia in the Korean general population: A retrospective analysis of population-based nationally representative data. Int J Rheum Dis 22(8):1435–1444. https://doi.org/10.1111/1756-185X.13632
Krishnan E, Lingala B, Bhalla V (2012) Low-level lead exposure and the prevalence of gout: an observational study. Ann Intern Med 157(4):233–241. https://doi.org/10.7326/0003-4819-157-4-201208210-00003
Kuo CC, Weaver V, Fadrowski JJ et al (2015) Arsenic exposure, hyperuricemia, and gout in US adults. Environ Int 76:32–40. https://doi.org/10.1016/j.envint.2014.11.015
Lai LH, Chou SY, Wu FY et al (2008) Renal dysfunction and hyperuricemia with low blood lead levels and ethnicity in community-based study. Sci Total Environ 401(1–3):39–43. https://doi.org/10.1016/j.scitotenv.2008.04.004
Lee D, Choi WJ, Oh JS et al (2013) The relevance of hyperuricemia and metabolic syndrome and the effect of blood lead level on uric Acid concentration in steelmaking workers. Ann Occup Environ Med 25(1):27. https://doi.org/10.1186/2052-4374-25-27
Li CC, Lv YB, Chen C et al (2021) Association of blood arsenic level with hyperuricemia among elderly aged 65 years and older in 9 longevity areas of China. Chin J Prevent Med 55(1):60–65. https://doi.org/10.3760/cma.j.cn112150-20200720-01028
Liu Z, Ding X, Wu J et al (2019) Dose-response relationship between higher serum calcium level and higher prevalence of hyperuricemia: A cross-sectional study. Medicine 98(20):e15611. https://doi.org/10.1097/MD.0000000000015611
Hernández-Serrato MI, Fortoul TI, Rojas-Martínez R et al (2006) Lead blood concentrations and renal function evaluation: study in an exposed Mexican population. Environ Res 100(2):227–231. https://doi.org/10.1016/j.envres.2005.03.004
Wang Y, Wei J, Zeng C et al (2018) Association between serum magnesium concentration and metabolic syndrome, diabetes, hypertension and hyperuricaemia in knee osteoarthritis: a cross-sectional study in Hunan Province, China. BMJ Open 8(9):e019159. https://doi.org/10.1136/bmjopen-2017-019159
Wang Y, Yang Z, Wu J et al (2020) Associations of serum iron and ferritin with hyperuricemia and serum uric acid. Clin Rheumatol 39(12):3777–3785. https://doi.org/10.1007/s10067-020-05164-7
Wang T, Lv Z, Wen Y et al (2022) Associations of plasma multiple metals with risk of hyperuricemia: A cross-sectional study in a mid-aged and older population of China. Chemosphere 287(Pt 3):132305. https://doi.org/10.1016/j.chemosphere.2021.132305
Zeng C, Wang YL, Wei J et al (2015) Association between low serum magnesium concentration and hyperuricemia. Magnes Res 28(2):56–63. https://doi.org/10.1684/mrh.2015.0384
Zeng A, Li S, Zhou Y et al (2022) Association Between Low-Level Blood Cadmium Exposure and Hyperuricemia in the American General Population: a Cross-sectional Study. Biol Trace Elem Res 200(2):560–567. https://doi.org/10.1007/s12011-021-02700-7
Pan L, Li G, Li J et al (2022) Heavy metal enrichment in drinking water pipe scales and speciation change with water parameters. Sci Total Environ 806(Pt 2):150549. https://doi.org/10.1016/j.scitotenv.2021.150549
Ekong EB, Jaar BG, Weaver VM (2006) Lead-related nephrotoxicity: a review of the epidemiologic evidence. Kidney Int 70(12):2074–2084. https://doi.org/10.1038/sj.ki.5001809
Kshirsagar MS, Patil AJ, Research D (2019) Impact of Occupational Lead Exposure on Liver and Kidney Function Tests on Silver Jewellery Workers. J Clin Diagn Res 13(1). https://doi.org/10.7860/JCDR/2019/38084.12442
Tsou TC, Chao HR, Yeh SC et al (2011) Zinc induces chemokine and inflammatory cytokine release from human promonocytes. J Hazard Mater 196:335–341. https://doi.org/10.1016/j.jhazmat.2011.09.035
Marreiro DD, Cruz KJ, Morais JB et al (2017) Zinc and Oxidative Stress: Current Mechanisms. Antioxidants (Basel) 6(2):24. https://doi.org/10.3390/antiox6020024
Dobrakowski M, Pawlas N, Kasperczyk A et al (2017) Oxidative DNA damage and oxidative stress in lead-exposed workers. Hum Exp Toxicol 36(7):744–754. https://doi.org/10.1177/0960327116665674
Liu G, Wang ZK, Wang ZY et al (2016) Mitochondrial permeability transition and its regulatory components are implicated in apoptosis of primary cultures of rat proximal tubular cells exposed to lead. Arch Toxicol 90(5):1193–1209. https://doi.org/10.1007/s00204-015-1547-0
Loghman-Adham M (1997) Renal effects of environmental and occupational lead exposure. Environ Health Perspect 105(9):928–938. https://doi.org/10.1289/ehp.97105928
Sabath E, Robles-Osorio ML (2012) Renal health and the environment: heavy metal nephrotoxicity. Nefrologia 32(3):279–286. https://doi.org/10.3265/Nefrologia.pre2012.Jan.10928
Wang W, Wang Q, Zou Z et al (2020) Human arsenic exposure and lung function impairment in coal-burning areas in Guizhou, China. Ecotoxicol Environ Saf 190:110174. https://doi.org/10.1016/j.ecoenv.2020.110174
Bai AM, Li Q, Li Y et al (2022) Investigation into environmental selenium and arsenic levels and arseniasis prevalence in an arsenic-affected coal-burning area. Front Nutr 9:922481. https://doi.org/10.3389/fnut.2022.922481
Gao W, Tong L, Zhao S et al (2022) Exposure to Cadmium, Lead, Mercury, and Arsenic and Uric Acid Levels: Results from NHANES 2007–2016. Biol Trace Elem Res. Advance online publication https://doi.org/10.1007/s12011-022-03309-0
Al-Brakati AY, Kassab RB, Lokman MS et al (2019) Role of thymoquinone and ebselen in the prevention of sodium arsenite-induced nephrotoxicity in female rats. Hum Exp Toxicol 38(4):482–493. https://doi.org/10.1177/0960327118818246
Prakash C, Chhikara S, Kumar V (2022) Mitochondrial Dysfunction in Arsenic-Induced Hepatotoxicity: Pathogenic and Therapeutic Implications. Biol Trace Elem Res 200(1):261–270. https://doi.org/10.1007/s12011-021-02624-2
Cormick G, Belizán JM (2019) Calcium Intake and Health. Nutrients 11(7):1606. https://doi.org/10.3390/nu11071606
Coe FL, Worcester EM, Evan AP (2016) Idiopathic hypercalciuria and formation of calcium renal stones. Nat Rev Nephrol 12(9):519–533. https://doi.org/10.1038/nrneph.2016.101
Khan SR (2013) Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations. J Urol 189(3):803–811. https://doi.org/10.1016/j.juro.2012.05.078
Li X, Ma J, Shi W et al (2016) Calcium Oxalate Induces Renal Injury through Calcium-Sensing Receptor. Oxid Med Cell Longev 2016:5203801. https://doi.org/10.1155/2016/5203801
Cole LK, Sparagna GC, Dolinsky VW et al (2022) Altered cardiolipin metabolism is associated with cardiac mitochondrial dysfunction in pulmonary vascular remodeled perinatal rat pups. PLoS One 17(2):e0263520. https://doi.org/10.1371/journal.pone.0263520
Vu TT, Dieterich P, Vu TT, Deussen A (2019) Docosahexaenoic acid reduces adenosine triphosphate-induced calcium influx via inhibition of store-operated calcium channels and enhances baseline endothelial nitric oxide synthase phosphorylation in human endothelial cells. Korean J Physiol Pharmacol 23(5):345–356. https://doi.org/10.4196/kjpp.2019.23.5.345
Tewari D, Sah AN, Bawari S et al (2021) Role of Nitric Oxide in Neurodegeneration: Function, Regulation, and Inhibition. Curr Neuropharmacol 19(2):114–126. https://doi.org/10.2174/1570159X18666200429001549
Schaefer HR, Dennis S, Fitzpatrick S (2020) Cadmium: Mitigation strategies to reduce dietary exposure. J Food Sci 85(2):260–267. https://doi.org/10.1111/1750-3841.14997
Genchi G, Sinicropi MS, Lauria G et al (2020) The Effects of Cadmium Toxicity. Int J Environ Res Public Health 17(11):3782. https://doi.org/10.3390/ijerph17113782
Shaikh ZA, Smith LM (1984) Biological indicators of cadmium exposure and toxicity. Experientia 40(1):36–43. https://doi.org/10.1007/BF01959100
Johri N, Jacquillet G, Unwin R (2010) Heavy metal poisoning: the effects of cadmium on the kidney. Biometals 23(5):783–792. https://doi.org/10.1007/s10534-010-9328-y
Nemmiche S (2017) Oxidative Signaling Response to Cadmium Exposure. Toxicol Sci 156(1):4–10. https://doi.org/10.1093/toxsci/kfw222
Wang SH, Shih YL, Ko WC et al (2008) Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway. Cell Mol Life Sci 65(22):3640–3652. https://doi.org/10.1007/s00018-008-8383-9
Pavón N, Buelna-Chontal M, Macías-López A et al (2019) On the oxidative damage by cadmium to kidney mitochondrial functions. Biochem Cell Biol 97(2):187–192. https://doi.org/10.1139/bcb-2018-0196
Johnson JL, Coyne KE, Rajagopalan KV et al (2001) Molybdopterin synthase mutations in a mild case of molybdenum cofactor deficiency. Am J Med Genet 104(2):169–173. https://doi.org/10.1002/1096-8628(20011122)104:2<169::aid-ajmg1603>3.0.co;2-8
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/114.9.1652
Seldén AI, Berg NP, Söderbergh A et al (2005) Occupational molybdenum exposure and a gouty electrician. Occup Med (Lond) 55(2):145–148. https://doi.org/10.1093/occmed/kqi018
Rasheed H, Kay P, Slack R et al (2019) Assessment of arsenic species in human hair, toenail and urine and their association with water and staple food. J Expo Sci Environ Epidemiol 29(5):624–632. https://doi.org/10.1038/s41370-018-0056-7
Salcedo-Bellido I, Gutiérrez-González E, García-Esquinas E et al (2021) Toxic metals in toenails as biomarkers of exposure: A review. Environ Res 197:111028. https://doi.org/10.1016/j.envres.2021.111028
Wu X, Cobbina SJ, Mao G et al (2016) A review of toxicity and mechanisms of individual and mixtures of heavy metals in the environment. Environ Sci Pollut Res Int 23(9):8244–8259. https://doi.org/10.1007/s11356-016-6333-x
Lin X, Gu Y, Zhou Q et al (2016) Combined toxicity of heavy metal mixtures in liver cells. J Appl Toxicol 36(9):1163–1172. https://doi.org/10.1002/jat.3283
Acknowledgements
The authors thank AiMi Academic Services (www.aimieditor.com) for the English language editing and review services.
Author information
Authors and Affiliations
Contributions
Tingting Gu conceived the study design; Tingting Gu, Guorong Cao, Nannan Zhang, Miao Luo, Ting Xue and Rongchun Hou searched and selected the articles, extracted, analyzed and interpreted the data; Tingting Gu and Guorong Cao drafted the manuscript; Min Leng revised the manuscript critically for important intellectual content. All authors approved the final version of the manuscript and agreed to be responsible for all aspects of the work. The authors had no conflicts of interest.
Corresponding author
Ethics declarations
Conflict of interest
None
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Gu, T., Cao, G., Luo, M. et al. A systematic review and meta-analysis of the hyperuricemia risk from certain metals. Clin Rheumatol 41, 3641–3660 (2022). https://doi.org/10.1007/s10067-022-06362-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-022-06362-1