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Relationship between serum nickel and homocysteine concentration in hemodialysis patients
Monika Katko1, Ildiko Kiss, Istvan Karpati
1First Department of Medicine, Medical and Health Science Center, Debrecen, Hungary. vargazs@internal.med.unideb.hu
Insights
In hemodialysis patients, lower nickel and higher folate and vitamin B12 levels correlate with lower homocysteine. Nickel inhibits homocysteine production in human cells, suggesting a role in the methionine-folate cycle.
Area of Science:
- Biochemistry
- Nephrology
- Trace Element Metabolism
Background:
- Severe hyperhomocysteinemia (HHC) is linked to atherosclerosis and cardiovascular disease, a leading cause of death in hemodialysis (HD) patients.
- Trace elements like cobalt, copper, iron, and nickel have shown potential in ameliorating HHC in animal models.
- The relationship between plasma total homocysteine (tHcy) and trace elements in HD patients remains under-investigated.
Purpose of the Study:
- To investigate the correlations between plasma total homocysteine (tHcy) and various trace elements (cobalt, copper, iron, nickel) in hemodialysis patients.
- To explore the association of tHcy with key vitamins (folate, vitamin B12) and other laboratory parameters in HD patients.
- To assess the in vitro effect of nickel and cobalt on homocysteine production in human peripheral mononuclear cells (PBMCs).
Main Methods:
- Measured plasma tHcy, folate, vitamin B12, trace elements (cobalt, copper, iron, nickel), and other laboratory parameters in 122 HD patients.
- Grouped patients based on tHcy levels to compare trace element and vitamin concentrations.
- Performed univariate regression analysis to identify correlations between tHcy and measured parameters.
- Assessed the impact of nickel and cobalt on homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs.
Main Results:
- Patients with lower tHcy exhibited higher levels of nickel, folate, and vitamin B12, and lower iron levels compared to those with higher tHcy.
- Univariate regression revealed negative correlations between tHcy and folate, vitamin B12, nickel, and C-reactive protein (CRP).
- tHcy positively correlated with serum albumin and hemoglobin.
- Nickel, but not cobalt, significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs at concentrations relevant to HD patients.
Conclusions:
- Nickel may play a role in regulating the methionine-folate cycle in humans, similar to findings in animal studies.
- Lower nickel and higher folate and vitamin B12 levels are associated with lower tHcy in hemodialysis patients.
- These findings highlight potential therapeutic targets for managing HHC and cardiovascular risk in HD populations.
Abstract:
Severe hyperhomocysteinemia (HHC) is associated with atherosclerosis. In hemodialysis (HD) patients, one of the main causes of death is cardiovascular disease. In animals, trace elements such as cobalt, copper, iron, and nickel ameliorated vitamin B(12) deficiency-induced HHC. However, correlations between plasma total homocysteine (tHcy) and trace elements in HD patients have not been investigated. Therefore, tHcy, folate, vitamin B(12), trace elements (cobalt, copper, iron, and nickel), and some laboratory parameters such as serum total protein, albumin, transferrin, ferritin, C-reactive protein (CRP), and interleukin-6 concentrations were determined in 122 hemodialysis patients. When patients were divided into groups according to their tHcy, we found no significant differences in concentrations of cobalt, copper, and total protein, while nickel was higher, and folate, vitamin B(12), and iron were lower in patients with lower than higher tHcy. In univariate regression analysis, tHcy negatively correlated with concentrations of folate (r = -0.302, p < 0.006), vitamin B(12) (r = -0.347, p < 0.0001), nickel (r = -0.289, p < 0.006), and CRP (r = -0.230, p < 0.02) and positively with serum albumin (r = 0.316, p < 0.0004) and hemoglobin (r = 0.329, p < 0.0001) values. No relationship between tHcy and serum concentrations of cobalt, copper, iron, or other laboratory parameters was found in HD patients. The effect of cobalt and nickel on homocysteine production was assessed in human peripheral mononuclear cells (PBMCs). Nickel but not cobalt at concentrations found in HD patients significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs. These results suggest that nickel might also be involved in the regulation of the methionine-folate cycle in humans, as was demonstrated in animal experiments.
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