The level of blood lead, zinc and relationship with the metallothionein gene polymorphism in chronic kidney failure

Authors

DOI:

https://doi.org/10.22141/2307-1257.14.3.2025.538

Keywords:

chronic kidney disease, metallothionein gene polymorphism, lead exposure, zinc deficiency, gene SNP rs28366003, hemodialysis

Abstract

Background. Chronic kidney disease is defined by renal damage or an estimated glomerular filtration rate less than 60 ml/min/1.73 m2. Lead is a ubiquitous environmental factor that can contribute to lengthy clinical complications in individuals with chronic kidney disease. They can be exposed to changes in zinc homeostasis. The MT2A gene also expresses a wide range of physiological and pathological effects. Materials and methods. This study involved 60 blood samples from individuals with kidney disease on hemodialysis, and 60 samples from apparently healthy individuals as a control. The purpose was to identify the molecular character of the genotype of the MT2A gene SNP (A>G) (rs28366003) in a cohort of chronic kidney disease subjects and apparently healthy controls. Results. Blood lead and zinc serum levels were compared between patients and healthy controls by flame atomic absorption spectrophotometry. Lead contents were significantly and considerably higher, with significant differences (p > 0.01) between the patient cohort and the healthy controls, while serum zinc was significantly decreased. Males are more affected than females with chronic kidney disease, and individuals older than 40 years had a greater risk of complications. Hypertension has a meaningful positive relation to chronic kidney disease, and it is therefore considered a possible risk factor. The rs28366003 A>G genotype associated with increased risk of kidney disease in Iraqi patients demonstrated considerable variation. The median age of kidney disease patients was 20 to 69 years. Genotypes and allele frequencies of rs28366003, A>G in the kidney disease population: 51.7 % (n = 31) were wild-type (AA), 33.3 % (n = 20) were heterozygous (AG) and 15 % (n = 9) were homozygous (GG). The allele frequencies of A and G were 68.3 and 31.7 %. Conclusions. Thus, the drop in zinc levels and the harmful increase in blood lead in chronic kidney failure patients who possess SNP variants of the MT2A gene, specifically rs28366003, may be involved in kidney disease susceptibility.

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References

Hamid RH, Al-Jumaily RMKh. Evaluation of Oxidative Stress Activity, DNA Damage and Global DNA Methylation among Patients with Chronic Kidney Disease. Iraqi J Sci. 2024;65(9):4963-4972. doi: 10.24996/ijs.2024.65.9.13.

Mahdi Al-Shattawi SS, Al-Jumili EF, Al-Kawaz UMR. Pin1 Gene Expression and Some Biochemical Parameters in Iraqi Population with Chronic Kidney Disease. Iraqi J Biotechnol. 2024;23(2):105-111.

AL-Razak MJA, Al Saadi BQH, Al Saedi AJH. Investigate Some Biochemical Parameters and Impact of NOS3 Gene Polymorphism among Iraqi Patients with Chronic Kidney Disease. Iraqi J Biotechnol. 2025;24(1):243-252.

Al-Jumaili RA, Al-Jumaili EF, Ramadhan OM. Role of Calcium Sensing Receptor Gene Polymorphism r1801725 in the Evaluation of Kidney Disease. Iraqi J Biotechnol. 2024;23(1):235-240.

Attia RI, Naji Abed NA. Evaluation of Some Biochemical Parameters and the Effect of Oxidative Stress During Hemodialysis in Patients with Chronic Renal Disease. Biochem Cell Arch. 2021;21(1):405.

Abdul-Jabbar MA, Kadhim DJ. Adherence to Different Treatment Modalities among Patients on Maintenance Hemodialysis. Iraqi J Pharm Sci. 2022;31(1):95-101. doi: 10.31351/vol31iss1pp95-101.

Al-Shibly KH, Al-Diwan JK. Effect of the Dietary Protein Intake on Urea Reduction Rate in Patients on Maintenance Hemodialysis in Merjan Teaching Hospital. Med J Babylon. 2022;19(2):244-249. doi: 10.4103/MJBL.MJBL_19_22.

Narayanan M, Setia S. Chronic Kidney Disease. In: Jackson M, Huang R, Kaplan E, Mookherjee S, editors. Perioperative Medicine Consult Handbook. Cham: Springer; 2020. 301-305 pp.doi: 10.1007/978-3-030-19704-9_38.

Filler G, Felder S. Trace elements in dialysis. Pediatr Nephrol. 2014 Aug;29(8):1329-1335. doi: 10.1007/s00467-013-2585-6.

Jebur NJ, Yahya RN. The Actual Benefits of Zinc for Cardiovascular Diseases: Mini Review. Al-Rafidain J Med Sci. 2022 Jul-Dec;3:82-86. doi: 10.54133/ajms.v3i.92.

Marreiro DD, Cruz KJ, Morais JB, Beserra JB, Severo JS, de Oliveira AR. Zinc and Oxidative Stress: Current Mechanisms. Antioxidants (Basel). 2017 Mar 29;6(2):24. doi: 10.3390/antiox6020024.

Gao B, Chi L, Mahbub R, et al. Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways. Chem Res Toxicol. 2017 Apr 17;30(4):996-1005. doi: 10.1021/acs.chemrestox.6b00401.

Ekong EB, Jaar BG, Weaver VM. Lead-related nephrotoxicity: a review of the epidemiologic evidence. Kidney Int. 2006 Dec;70(12):2074-2084. doi: 10.1038/sj.ki.5001809.

Yang R, Roshani D, Gao B, Li P, Shang N. Metallothionein: A Comprehensive Review of Its Classification, Structure, Biological Functions, and Applications. Antioxidants (Basel). 2024 Jul 9;13(7):825. doi: 10.3390/antiox13070825.

Hamed OM, Khalil MI, Alsaffar RS. Metallothionein Gene Polymorphism Is Considered to Be a Risk Factor for Chronic Diseases. Int J Health Sci. 2022;6(S5):1691-1692. doi: 10.53730/ijhs.v6nS5.9021.

Leierer J, Rudnicki M, Braniff SJ, et al. Metallothioneins and renal ageing. Nephrol Dial Transplant. 2016 Sep;31(9):1444-1452. doi: 10.1093/ndt/gfv451.

George D, Mallery P. IBM Statistics 26 Step by Step: A simple guide and reference. 16th ed. New York: Routledge; 2019. 402 p. doi: 10.4324/9780429056765.

Al-Jumaili RA, Al-Jumaili EF. Study of the causes of parathyroid hormone imbalance and some biochemical parameter in patients with chronic kidney disease. Rom J Diabetes Nutr Metab Dis. 2024;31(1):49-57. doi: 10.46389/rjd-2024-0049.

Rebhi F, Khadhar M, Sarra H, et al. Hypertension and Chronic Kidney Disease: A Close and Proportional Relationship. Nephrol Dial Transplant. 2023 Jun;38(Suppl 1):gfad063d_6789. doi: 10.1093/ndt/gfad063d_6789.

Elgenidy A, Amin MA, Awad AK, Husain-Syed F, Aly MG. Serum Zinc Levels in Chronic Kidney Disease Patients, Hemodialysis Patients, and Healthy Controls: Systematic Review and Meta-Analysis. J Ren Nutr. 2023 Jan;33(1):103-115. doi: 10.1053/j.jrn.2022.04.004.

Yao S, Xu D. Relationships between blood concentrations of cadmium, lead, mercury, selenium, and manganese and the risk of chronic kidney disease: a cross-sectional study based on NHANES 2011-2018. Arch Med Sci. 2024 Dec 13;20(6):1822-1830. doi: 10.5114/aoms/181508.

AlAni HT, Al-Lami MQ. Evaluation of Some Biochemical and Hematological Parameters in Patients with Chronic Kidney Disease. J Fac Med Baghdad. 2024;66(2):154-161. doi:10.32007/jfacmedbagdad.2269.

Duff R, Awofala O, Arshad MT, et al. Global health inequalities of chronic kidney disease: a meta-analysis. Nephrol Dial Transplant. 2024 Sep 27;39(10):1692-1709. doi: 10.1093/ndt/gfae048.

Fradelos EC. The Effect of Clinical and Demographic Factors on Quality of Life in End-Stage Renal Disease: A Multicenter Cross-Sectional Study. J Ren Hepat Disord. 2020;4(1):1-9. doi: 10.15586/jrenhep.2020.58.

Baqer HM, Jabur F, Kadhum S. Impact of End Stage Renal Disease Upon Physical Activity for Adult Patients Undergoing Hemodialysis at AL-Najaf Governorate Hospitals. J Pharm Sci Res. 2018;10(5):1170-1174.

Saber A, Tahami AN, Najafipour H, Azmandian J. Assessment of Prevalence of Chronic Kidney Disease and Its Predisposing Factors in Kerman City. Nephro-Urol Monthly. 2017;9(2):e13113. doi: 10.5812/numonthly.41794.

Swastika KD, Tarigan RR. Hypertension on Dialysis Patients: Influence Factors and Management. J Endocrinol Tropic Med Inf Dis. 2022;4(4):176-190. doi: 10.32734/jetromi.v4i4.14734.

Ku E, Lee BJ, Wei J, Weir MR. Hypertension in CKD: Core Curriculum 2019. Am J Kidney Dis. 2019 Jul;74(1):120-131. doi: 10.1053/j.ajkd.2018.12.044.

Abdollahi A, Ghahramani A, Ghahramani N. Zinc and Kidney Disease: A Review. Iran J Kidney Dis. 2022 Mar;16(2):79-87.

Tokuyama A, Kanda E, Itano S, et al. Effect of zinc deficiency on chronic kidney disease progression and effect modification by hypoalbuminemia. PLoS One. 2021 May 11;16(5):e0251554. doi: 10.1371/journal.pone.0251554.

Damianaki K, Lourenco JM, Braconnier P, et al. Renal handling of zinc in chronic kidney disease patients and the role of circulating zinc levels in renal function decline. Nephrol Dial Transplant. 2020 Jul 1;35(7):1163-1170. doi: 10.1093/ndt/gfz065.

Toida T, Toida R, Ebihara S, et al. Association between Serum Zinc Levels and Clinical Index or the Body Composition in Incident Hemodialysis Patients. Nutrients. 2020 Oct 19;12(10):3187. doi: 10.3390/nu12103187.

Harari F, Sallsten G, Christensson A, et al. Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort. Am J Kidney Dis. 2018 Sep;72(3):381-389. doi: 10.1053/j.ajkd.2018.02.358.

Jalili C, Kazemi M, Cheng H, et al. Associations between exposure to heavy metals and the risk of chronic kidney disease: a systematic review and meta-analysis. Crit Rev Toxicol. 2021 Feb;51(2):165-182. doi: 10.1080/10408444.2021.1891196.

Ivanova M, Dyadyk O, Ivanov D, Clerici F, Smith A, Magni F. Matrix-assisted laser desorption/ionization mass spectrometry imaging to uncover protein alterations associated with the progression of IgA nephropathy. Virchows Arch. 2020 Jun;476(6):903-914. doi: 10.1007/s00428-019-02705-7.

Mira FS, Oliveiros B, Carreira IM, Alves R, Ribeiro IP. Genetic Variants Related to Increased CKD Progression-A Systematic Review. Biology (Basel). 2025 Jan 14;14(1):68. doi: 10.3390/biology14010068.

Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V. Chronic kidney disease. Lancet. 2021 Aug 28;398(10302):786-802. doi: 10.1016/S0140-6736(21)00519-5.

Hattori Y, Naito M, Satoh M, et al. Metallothionein MT2A A-5G Polymorphism as a Risk Factor for Chronic Kidney Disease and Diabetes: Cross-Sectional and Cohort Studies. Toxicol Sci. 2016 Jul;152(1):181-193. doi: 10.1093/toxsci/kfw080.

Tamay-Cach F, Quintana-Pérez JC, Trujillo-Ferrara JG, et al. A review of the impact of oxidative stress and some antioxidant therapies on renal damage. Ren Fail. 2016;38(2):171-175. doi: 10.3109/0886022X.2015.1120097.

Kayaaltı Z, Aliyev V, Söylemezoğlu T. The potential effect of metallothionein 2A -5A/G single nucleotide polymorphism on blood cadmium, lead, zinc and copper levels. Toxicol Appl Pharmacol. 2011 Oct 1;256(1):1-7. doi: 10.1016/j.taap.2011.06.023.

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Published

2025-08-09

How to Cite

Nasser, A. M., & Al-Jumaili, E. F. (2025). The level of blood lead, zinc and relationship with the metallothionein gene polymorphism in chronic kidney failure. KIDNEYS, 14(3), 191–198. https://doi.org/10.22141/2307-1257.14.3.2025.538

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Original Articles