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Copper and Zinc Serum Level in Patients Receiving Hemodialysis

Correspondence Address: Akbar Kazemi Research Center for Social Determinant of Health, Jahrom University of Medical Sciences, Jahrom, Iran E-mail: sotoodehj2002@yahoo.com Abstract: Decreased kidney function can accumulate trace elements. Increased trace elements can have toxic features. On the other hand, studies are showing that concentration of some trace elements could be decreased in chronic kidney disease patients as well. Because these patients are at risk for alterations of trace elements, we measured serum level of zinc and copper trace elements in hemodialysis patients and compare it with the control group. We analyzed the trace elements' copper and zinc concentration in the whole blood of 52 ESRD patients who were treated with hemodialysis as case group and also of 52 age and sex matched healthy people as control group. Whole blood trace element concentration was determined by atomic absorption spectrometry. The serum concentrations of zinc and copper were significantly lower in case group compared to control group. The serum concentration of zinc and copper trace elements in end-stage renal failure patients is disturbed. Due to the discrepancy in findings of different studies, further studies in large scale are recommended to determine the serum concentration of trace elements in these patients.


Introduction
Uremia is recognized by functional and biochemical disturbances that are primarily a result of reduced kidney capacity to clear body from organic solutes. Most studies on uremic toxicity have focused on retention and removal of these organic compounds. However, subtle changes in the concentrations of inorganic compounds, including trace elements, may also cause functional or biochemical disturbances (Vanholder et al., 2002;Prodanchuk et al., 2013).
In End-Stage Renal Disease (ESRD) patients, different factors affect whole blood and serum level of trace elements, such as increased oral intake, failure of renal excretion, grade of renal failure and metabolic changesrelated with renal failure (Miura et al., 2002).
Hemodialysis is the most common modality of renal replacement therapy. Unfortunately, dialysis is associated with considerable morbidity and mortality due to cardiovascular disease and infection (Henderson and Beans, 1978).
Hemodialysis patients are at risk for both deficiency and accumulation of trace elements, depending on dietary intake, removal by dialysis, the composition of the source water used for hemodialysis and residual kidney function (D'haese and De Broe, 1996;Zima et al., 1999).
The trace elements have a role in infection control through the immune system function. Deficiency of micronutrients like vitamins, iron, zinc and copper are the most important reasons for immunodeficiency (Foreman et al., 1996).
Regarding what has been said, it can be concluded that copper as a micronutrient has a vital role. In addition, reduced serum level of copper (Cunningham-Rundles et al., 2005) and zinc (Hsieh et al., 2006) in dialysis patients, Therefore, serum levels copper and zinc should be determined in hemodialysis patients.
Achieved information about trace element disorders in ESRD patients receiving hemodialysis could assist in the process of developing a microelement improvement approach. Thus, it would recover the nutritional status of these patients.
In this research, we intend to determine the serum level of copper and zinc in hemodialysis patients and compare with serum level of these trace elements in healthy people.

Materials and Methods
This case-control study was carried out on dialysis patients referring to Jahrom Dialysis Center May 2013 to August 23, 2013. Fifty two dialysis patients visiting Jahrom Dialysis Center as case group and 52 sex and age matched healthy people (having normal serum creatinine and BUN levels) as control group were enrolled to this study.
This research work was approved by ethics research committee of Jahrom University of medical sciences.
Blood samples (3cc) of the both groups were taken and isolated sera were kept at-20°C. Serum level copper and zinc were determined by atomic absorption method by Perkin-elemer A300.
All demographic information of the case and the control groups was kept confidential and all examinations were free of charge.
At the end, all checklist information was fed into SPSS16 and analyzed statically; using t-test, chi-square test and descriptive analysis.

Results
Among the 52 dialysis patients, 35 (67.30%) and 17 (32.70%) subjects were male and female, respectively, with the mean age of 57.75±4.26 years. In the control group, 34 (65.40%) and 18 (34.60%) subjects were male and female, respectively, with the mean age of 58.98±14.32 years. There was no statistically significant difference between the two groups in terms of mean age and gender frequency (p>0.100).
In the case group, dialysis therapy duration was 25.55±25.67 months.
The serum concentrations of zinc and copper were significantly lower in case group compared to control group (Table 1).
There was no statistically significant difference in serum level of copper between male and female in the case and the control groups (Table 2).
Also there was no statistically significant difference in serum level of zinc between male and female in the case and the control groups (Table 3).
The results showed an inverse relationship between the serum level of copper and zinc, with age in case group, but it was not statistically significant (r = -0.033, P = 0.819) and (r = -0.164, P = 0.244), respectively. The same result was observed in the control group (r = -0.036, P = 0.802) and (r = -0.075, P = 0.595) respectively for copper and zinc. An inverse relationship was observed between the serum level copper and zinc with duration of dialysis therapy in the case group. Patients with longer dialysis history had lower serum level of copper and zinc, which were statistically significant (r = -0.444, P=0.001) and (r = -0.330, P = 0.017), respectively.

Discussion
Our data shows that the decreasing amounts of the trace elements copper and zinc in blood levels is observed for hemodialysis patients, in comparison with healthy people. This result has an agreement with previous study in Spain (Cunningham-Rundles et al., 2005) and another research in Taiwan (Hsieh et al., 2006) but it is inconsistent with the result of Navarro-Alarcon study. Their findings showed that the zinc serum level in hemodialysis patients was higher than normal people, which was not statistically significant (Navarro-Alarcon et al., 2006). They attributed this to blood doping or release of copper in dialysis membrane (Oh and Meyerhoff, 2004;De La Torre et al., 2014).
In present study, there was no significant correlation between the serum level copper and zinc with the factors age and gender, which agreed with other studies (Navarro-Alarcon et al., 2006;Churchwell et al., 2007).
In this study, the serum level copper and zinc in female and male groups was not significantly different in the case and in the control groups. Similar results were observed in other research (Anees et al., 2011). Yet, findings of Navarro-Alarcon et al. (2006) contradicted ours, as that level was significantly higher among the investigated men than women.
Incorrect implementation of dialysis process, including disorder in the concentration ratio of blood and dialysis fluid or in permeability of dialysis membrane, can reduce the level of trace element. However, other cases including loss of appetite and decreasing in daily food intake can be other influential reasons. Paying attention to this further signifies the very important and vital role of such trace elements (copper, zinc) for these patients (Anees et al., 2011).
Also, some studies said that the copper serum level did change during dialysis process (Johnson and Kays, 1990;Ikee et al., 2012;De la Torre et al., 2014).
Regarding on this matter, the relationship between the dialysis processes with trace elements serum level is controversial. Although, the findings of this study show the level reduction, further investigations are recommended.
In this study, an inverse association was observed between the serum level copper and zinc and age in the both groups. Since this relationship was not significant in any of the two investigated groups, it could be concluded that aging did not affect the copper and zinc serum level.
In this study, an inverse statistically significant relationship was observed between the serum level of copper and zinc with the history hemodialysis therapy in the case group, which was consistent with previous study (Lönnerdal, 1998;Bhogade et al., 2013). On the other hand, other results of this study were inconsistent with the result of Kaliuzhinas research (Kaliuzhina et al., 2005).
Some important roles of copper and zinc in the body include: The presence in biological enzymes as cofactors including anti-oxidant, electron carriers, clotting enzymes, etc. (Kaliuzhina et al., 2005); its role in human health like infection control through the immune system, inhibition of viral replication (Girndt et al., 1993), improving the function of T lymphocyte (Vacher-Coponat et al., 2008), in vivo cooperation for cell-mediated immune response.
Although, hemodialysis facilities the symptoms and signs of ESRD, it does not change the disease natural flow and faces the patients with several complications. Some of those problems are the direct outcomes of the hemodialysis process.

Conclusion
This study aims at investigating the serum level trace elements in ESRD, since copper and zinc have an important role in health, as mentioned. Therefore, disorder in their level can lead to several problems to the dialysis patients who are prone to several infections and other diseases. According to our results, the serum level of copper and zinc were significantly lower in the case group than healthy people. Therefore, it can be concluded that the use of copper and zinc supplement for such patients is essential for preventing further complications. However, further investigations in that area are recommended.