Diyaliz Hastalarında Yükselmiş Kadmiyum Düzeyleri ve Bunların İnflamasyon, Oksidatif Stres ve Malnütrisyon ile İlişkisi

Abstract

Amaç: Bu çalışmanın amacı, hemodiyaliz (HD) ve periton diyalizi (PD) hastaları ile sağlıklı bireyler arasında kandaki kadmiyum (Cd) düzeylerini karşılaştırmak ve Cd düzeylerinin inflamatuar, oksidatif ve beslenme belirteçleri ile ilişkisini değerlendirmektir. Gereç ve Yöntemler: Bu kesitsel çalışmaya 61 diyaliz hastası (31 HD, 30 PD) ve 15 sağlıklı kontrol dahil edilmiştir. Tam kan Cd düzeyleri atomik absorbsiyon spektrometrisi ile ölçülmüş ve hemoglobin düzeyine göre düzeltilmiştir (cCd). Serum interlökin-6 (IL-6), yüksek duyarlılıklı C-reaktif protein (hs-CRP), malondialdehit (MDA) ve ileri oksidasyon protein ürünleri (AOPP) inflamasyon ve oksidatif stresin göstergeleri olarak analiz edilmiştir. Bulgular: Hem HD hem de PD hastalarında, tam kan Cd ve cCd düzeyleri, sağlıklı kontrollere kıyasla anlamlı derecede yüksekti (sırasıyla, p=0,021 ve p=0,001), ancak iki diyaliz yöntemi arasında anlamlı bir fark saptanmamıştır. Korelasyon analizlerinde Cd düzeylerinin inflamasyon ve oksidatif stres belirteçleri olan IL-6 (rs=0,338, p=0,003), hs-CRP (rs=0,464, p=0,001), MDA (rs=0,464, p=0,001) ve AOPP (rs=0,454, p=0,001) ile pozitif yönde korelasyon gösterdiği belirlenmiştir. Buna karşılık, cCd düzeylerinin serum albümin konsantrasyonları ile negatif yönde anlamlı korelasyon gösterdiği saptanmıştır (rs=-0,454, p=0,001). Sonuç: Cd birikimi, tedavi yönteminden bağımsız olarak diyaliz hastalarında belirgin şekilde artmıştır ve bu sistemik inflamasyon, oksidatif hasar ve bozulmuş beslenme durumu ile yakından ilişkilidir. Çevresel Cd maruziyeti, kronik böbrek hastalığında (KBH) olumsuz klinik sonuçlara katkıda bulunan yeterince tanınmamış bir faktör olabilir ve Cd yükünü azaltmaya yönelik önleyici stratejiler, bu hasta grubunda prognozu iyileştirmeye katkı sağlayabilir.

Keywords

• Kadmiyum
• Kronik böbrek hastalığı
• Hemodiyaliz
• Periton diyalizi
• İnflamasyon
• Oksidatif stres
• Malnütrisyon

Elevated Cadmium Levels in Dialysis Patients and Their Links to Inflammation, Oxidative Stress, and Malnutrition

Abstract

Aim: This study aimed to compare blood cadmium (Cd) levels between hemodialysis (HD) and peritoneal dialysis (PD) patients and healthy controls, and to evaluate the associations between Cd levels and inflammatory, oxidative, and nutritional markers. Material and Methods: Sixty-one dialysis patients (31 HD, 30 PD) and 15 healthy controls were included in this cross-sectional study. Whole-blood Cd was measured by atomic absorption spectrometry and corrected for hemoglobin (cCd). Serum interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) were analyzed as indicators of inflammation and oxidative stress. Results: Both whole-blood Cd and cCd levels were significantly higher in both HD and PD patients compared with healthy controls (p=0.021 and p=0.001, respectively), while no statistically significant difference was observed between the two dialysis modalities. Correlation analyses demonstrated that Cd levels were positively correlated with inflammatory and oxidative stress markers, including IL-6 (rs=0.338, p=0.003), hs-CRP (rs=0.464, p=0.001), MDA (rs=0.464, p=0.001), and AOPP (rs=0.454, p<0.001). In contrast, cCd levels showed a significant negative correlation with serum albumin concentrations (rs=-0.454, p=0.001). Conclusion: Cd accumulation is markedly increased in dialysis patients regardless of treatment modality and is closely linked to systemic inflammation, oxidative damage, and reduced nutritional status. Environmental Cd exposure may represent an under-recognized contributor to adverse clinical outcomes in chronic kidney disease (CKD), and preventive strategies to minimize Cd burden may help improve prognosis in this population.

Keywords

• Cadmium
• Chronic kidney disease
• Hemodialysis
• Peritoneal dialysis
• Inflammation
• Oxidative stress
• Malnutrition

References

1. Xie Y, Liu F, Zhang X, Jin Y, Li Q, Shen H, et al. Benefits and risks of essential trace elements in chronic kidney disease: a narrative review. Ann Transl Med. 2022;10(24):1400.
2. Fernando BNT, Nanayakkara N, Chandrajith R, Abeysundara HTK, Herath D. Distinctive patterns of trace elements in chronic kidney disease of uncertain etiology: comparative analysis across multiple control groups. Kidney Dial. 2025;5(1):11.
3. Hill NR, Fatoba ST, Oke JL, Hirst JA, O'Callaghan CA, Lasserson DS, et al. Global prevalence of chronic kidney disease - A systematic review and meta-analysis. PloS One. 2016;11(7):e0158765.
4. Charkiewicz AE, Omeljaniuk WJ, Nowak K, Garley M, Nikliński J. Cadmium toxicity and health effects-a brief summary. Molecules. 2023;28(18):6620.
5. Rafati Rahimzadeh M, Rafati Rahimzadeh M, Kazemi S, Moghadamnia AA. Cadmium toxicity and treatment: An update. Caspian J Intern Med. 2017;8(3):135-45.
6. Davidova S, Milushev V, Satchanska G. The mechanisms of cadmium toxicity in living organisms. Toxics. 2024;12(12):875.
7. Rasin P, Ashwathi A, Basheer SM, Haribabu J, Santibanez JF, Garrote CA, et al. Exposure to cadmium and its impacts on human health: A short review. J Hazard Mater Adv. 2025;17:100608.
8. Dai Y, Liu J, Liang N, Guo Z, Jin J, Bi C, et al. Phase partitioning and toxicity prediction of metals in blood plasma, platelets, leukocytes and erythrocytes. Ecotoxicol Environ Saf. 2025;303:118803.

9. Satarug S. Is chronic kidney disease due to cadmium exposure inevitable and can it be reversed? Biomedicines. 2024;12(4):718.
10. Prozialeck WC, Edwards JR, Woods JM. The vascular endothelium as a target of cadmium toxicity. Life Sci. 2006;79(16):1493-506.
11. Yang Y, Hassan MF, Ali W, Zou H, Liu Z, Ma Y. Effects of cadmium pollution on human health: A narrative review. Atmosphere. 2025;16(2):225.
12. Qu F, Zheng W. Cadmium exposure: mechanisms and pathways of toxicity and implications for human health. Toxics. 2024;12(6):388.
13. Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T, Jacobo-Albavera L. Endothelial dysfunction, inflammation and coronary artery disease: potential biomarkers and promising therapeutical approaches. Int J Mol Sci. 2021;22(8):3850.
14. López E, Arce C, Oset-Gasque MJ, Cañadas S, González MP. Cadmium induces reactive oxygen species generation and lipid peroxidation in cortical neurons in culture. Free Radic Biol Med. 2006;40(6):940-51.
15. Wang X, Dong B, Gan Q, Li J, Wu P, Guan Y, et al. Unraveling the vicious cycle: oxidative stress and neurotoxicity in neurodegenerative diseases. FASEB Bioadv. 2025;7(8):e70041.
16. Al-Naemi HA, Das SC. Cadmium-induced endothelial dysfunction mediated by asymmetric dimethylarginine. Environ Sci Pollut Res Int. 2020;27(14):16246-53.
17. Baaten CCFMJ, Vondenhoff S, Noels H. Endothelial cell dysfunction and increased cardiovascular risk in patients with chronic kidney disease. Circ Res. 2023;132(8):970-92.
18. Chen F, Lin H, Zhang Y, Zhang Y, Chen S. Investigating how blood cadmium levels influence cardiovascular health scores across sexes and dose responses. Front Public Health. 2024;12:1427905.
19. Vida C, Oliva C, Yuste C, Ceprián N, Caro PJ, Valera G, et al. Oxidative stress in patients with advanced CKD and renal replacement therapy: the key role of peripheral blood leukocytes. Antioxidants (Basel). 2021;10(7):1155.
20. Hsu CW, Lin JL, Lin-Tan DT, Huang WH, Chen KH, Yen TH. Association between blood cadmium levels and malnutrition in peritoneal dialysis. BMC Nephrol. 2014;15:17.
21. Hsu CW, Yen TH, Chen KH, Lin-Tan DT, Lin JL, Weng CH, et al. Effect of blood cadmium level on mortality in patients undergoing maintenance hemodialysis. Medicine (Baltimore). 2015;94(42):e1755.
22. Abernathy TV, Lee KB, Parker RJ, Reed E. The measurement of cadmium in biological materials, using graphite furnace atomic absorption spectrometry with Zeeman background correction. Oncol Rep. 1999;6(1):155-9.
23. Xu C, Li Z, Hao S, Zhang J, Li J, Liang K, et al. Association of blood cadmium levels with all-cause and cause-specific mortality among adults with non-alcoholic fatty liver disease: a prospective cohort study. Front Public Health. 2025;13:1573760.
24. Yan LJ, Allen DC. Cadmium-induced kidney injury: oxidative damage as a unifying mechanism. Biomolecules. 2021;11(11):1575.
25. Satarug S, C Gobe G, A Vesey D, Phelps KR. Cadmium and lead exposure, nephrotoxicity, and mortality. Toxics. 2020;8(4):86.
26. Moody EC, Coca SG, Sanders AP. Toxic metals and chronic kidney disease: a systematic review of recent literature. Curr Environ Health Rep. 2018;5(4):453-63.
27. Aslan Sirakaya H, Sipahioglu H, Cetinkaya A, Aydin K. Relationship between inflammatory markers (IL-6, neutrophil-lymphocyte ratio, and C-reactive protein-albumin ratio) and diabetic ketoacidosis severity: correlation with clinical outcomes. Medicina (Kaunas). 2025;61(2):321.
28. Cordiano R, Di Gioacchino M, Mangifesta R, Panzera C, Gangemi S, Minciullo PL. Malondialdehyde as a potential oxidative stress marker for allergy-oriented diseases: an update. Molecules. 2023;28(16):5979.
29. Assani MZ, Novac MB, Dijmărescu AL, Stroe-Ionescu AȘ, Boldeanu MV, Siloși I. Intersecting pathways of inflammation, oxidative stress, and atherogenesis in the evaluation of CKD: emerging biomarkers PCSK9, EPHX2, AOPPs, and TBARSs. Life (Basel). 2025;15(8):1287.
30. Ahmad A, Manjrekar P, Yadav C, Agarwal A, Srikantiah RM, Hegde A. Evaluation of ischemia-modified albumin, malondialdehyde, and advanced oxidative protein products as markers of vascular injury in diabetic nephropathy. Biomark Insights. 2016;11:63-8.
31. Kalantar-Zadeh K, Ficociello LH, Bazzanella J, Mullon C, Anger MS. Slipping through the pores: hypoalbuminemia and albumin loss during hemodialysis. Int J Nephrol Renovasc Dis. 2021;14:11-21.
32. Tobón-Cornejo S, Sanchez-Tapia M, Guizar-Heredia R, Velázquez Villegas L, Noriega LG, Furuzawa-Carballeda J, et al. Increased dietary protein stimulates amino acid catabolism via the gut microbiota and secondary bile acid production. Gut Microbes. 2025;17(1):2465896.
33. Pasini E, Corsetti G, Aquilani R, Romano C, Picca A, Calvani R, et al. Protein-amino acid metabolism disarrangements: The hidden enemy of chronic age-related conditions. Nutrients. 2018;10(4):391.
34. Aydin G, Topal C, Konur K, Ilmaz O. Effects of different peritoneal dialysis solutions on serum lipid levels and lipid profile in end-stage chronic kidney disease patients undergoing peritoneal dialysis. BMC Nephrol. 2025;26(1):483.
35. Kezić A, Gajić S, Ostojić AR, Bekić I, Bontić A, Pavlović J, et al. Glycemic control in patients with diabetes on peritoneal dialysis: from glucose sparing approach to glucose monitoring. Life (Basel). 2025;15(5):798.
36. Lee CC, Weng CH, Huang WH, Yen TH, Lin JL, Lin-Tan DT, et al. Association between blood cadmium levels and mortality in peritoneal dialysis. Medicine (Baltimore). 2016;95(19):e3717.
37. Bonanni A, Mannucci I, Verzola D, Sofia A, Saffioti S, Gianetta E, et al. Protein-energy wasting and mortality in chronic kidney disease. Int J Environ Res Public Health. 2011;8(5):1631-54.
38. Mihai S, Codrici E, Popescu ID, Enciu AM, Albulescu L, Necula LG, et al. Inflammation-related mechanisms in chronic kidney disease prediction, progression, and outcome. J Immunol Res. 2018;2018:2180373.
39. Liu J, Chen K, Tang M, Mu Q, Zhang S, Li J, et al. Oxidative stress and inflammation mediate the adverse effects of cadmium exposure on all-cause and cause-specific mortality in patients with diabetes and prediabetes. Cardiovasc Diabetol. 2025;24(1):145.