With recent advances studies of pathophysiology, inflammation and dysregulated immune responses have emerged as important factors contributing to the gradual loss of renal function in CKD patients [10]. Moreover, the risk of heart diseases and cancers increases markedly in CKD patients [11, 12]. Also, the CKD patients are at the risk of developing severe trace elements imbalances [13, 14]. Trace elements are indispensable and often combined with proteins, coenzyme, hormones and vitamins. In ESRD patients, many different factors affect the serum concentrations of trace elements, such as increased oral intake, failure of renal excretion, loss of appetite and metabolic alterations and so on. During dialysis processes some trace elements can accumulate because of dialysis fluid impurities, and others may move from blood to the dialysate, leading to deficiency [15].
In our study, plasma Fe, Cu and Mg trace element levels of CKD patients, were compared with control group and compared with each other. We found that plasma Fe have no statistically differences between patients and the control group. This may be attributed to the fact that we often supplement iron in CKD patients because most of them have anemia, especially in CKD5. Again there were no difference in plasma Cu and Mg, we analyze that the control and patients had the similar regional changes and dietary habits which soil and water contamination. Adversely, Serum Zn and Ca values were significantly lower in our CKD patients than the controls, and the tendency became more obvious as the disease progressed, especially in CKD5 patients. Zn is an essential component of various proteins and biomembrane [16]. Recent studies suggest that, both of the increased urinary zinc excretion and decreased intestinal zinc absorption may be the primary cause of hypozincemia in patients. Also dietary restrictions and anorexia lead to an insufficient micronutrient intake. Shrimpton[17] argue zinc deficiency is a leading cause of diseases in developing countries and is associated with immune deficiencies by impaired cell proliferation, abnormal T-cell function, and cytokine expression, all of which might contribute to the high risk of infection observed in uraemia patients. Meanwhile we found Zn amounts in HD and PD lower than other CKD patients. We think it is because of these patients are more seriously and renal replacement therapies consume more zinc. Ca is one of the most abundant mineral elements in human body, and the normal function of tissues and organs regulating various systems of human body depends on its existence. The person can become sensitive, emotional instability and attention deficit if they lack of Ca. In CKD patients the kidney damage leading to the body of phosphorus excretion disorder, on the other hand the diet excessive intake of phosphorus, so the combined with Ca induced deposition, it caused the loss of calcium and insufficient production of 1.25-(OH)2VitD3 which reduce calcium absorption. We found that the decrease in blood calcium is more significant in PD patients which were more likely to use low calcium dialysis fluid. These consequences consistent with several other investigators [18]. Miura et al. [19] compared serum Mg and Cu levels between HD patients and control groups and found no statistically significant differences. The results of Miura study also found Zn is lower in HD patients. But Krachler et al. [20]found elemental composition changes in plasma and observed a decrease in Mg levels over a 6-month period in uremia. Regulating trace element levels is essential to prevent some complications in HD patients. Differing results have been reported with respect to plasma levels of trace elements in HD patients. Tonelli et al [21] found low plasma Zn and high plasma Cu levels in HD patients compared with controls. The distribution of trace elements can be affected by insufficient dietary intake, anorexia, degrees of gastrointestinal absorption, and drug treatment, it lead to some clinical abnormalities in uremic patients (D’Haese [22] ).The uremic state, medication, the dialysis process, dietary intake, and the quality of water used for dialysis may contribute to such clinical abnormalities of trace elements [23]. Although recent improvements of technology in the dialysis can prevent some serious complications by changes in trace elements, problems still remained [24]. In our study, although dialysis treatment improved the survival of CKD patients, it had a limited effect on trace elements. Dialysis augments reduced renal function by removing metabolic waste products and maintaining the electrolyte balance and acid-base equilibrium. However, due to the possible risks present in HD, such as blood loss during treatment, dietary restrictions, anorexia, aluminum intoxication [25] and dialyzer biocompatibility [26], there is no effect in trace elements balance compared with No-dialysis patients. Although PD has advantages over HD in these respects [27], problems such as increased protein loss, excessive glucose intake and triglyceride abnormalities make it ineffective in restoring immune balance. Further investigation is required to identify new therapeutic agents or strategies to improve the patient’s microenvironment.
OS refers to an imbalance in the body oxidation and antioxidation, results in neutrophils inflammatory infiltrates, proteases secretion to increase, and produces a large number of oxide intermediate. Several studies have confirmed that the occurrence of complications in CKD such as accompany hypertension [26], disease of heart and nervous system lesions, OS is one of the important risk factors affecting prognosis of CKD [28]. SOD and MDA can be used to evaluate the body's resistance to oxidation and peroxidation level. In our study the Serum levels of MDA were significantly higher and SOD significantly lower in CKD patients than in controls. Meanwhile we found that Serum levels of MDA and SOD were be closely related with serum creatinine levels. The results reiterate that the severity of CKD correlates with the degree of OS. However, as the renal function deteriorates, OS response might impair renal function and the extent of renal damage could conceivably increase during progression of CKD. So we think that the OS reaction which caused by metabolic disorder and apoptosis may be involved in the development process of renal fibrosis. But serum levels of SOD were altered by dialysis treatment compared with no-dialysis, so we think replacement can improve the imbalance in the body oxidation and antioxidation system of CKD patients.
We also compared trace element levels and oxidant–antioxidant parameters and found that in patient groups, there was a significant positive correlation between serum levels of SOD with Ca (Fig. 3B, r = 0.273, P < 0.01), Zn (Fig. 3A, r = 0.277, P < 0.01). Adversely, there was a significant negative correlation between serum levels of MDA with Ca(Fig. 3C, r=-0.282,P < 0.01, Zn༈Fig. 3D, r=-0.358༌P < 0.01)as well as a positive correlation between MDA and serum Cu, but the relationship did not quite reach statistical significance. According to the above description, OS is one of the important risk factors affecting prognosis of CKD, so we have reasons to regard that Zn and Cu are closely influenced by OS. Cu is a transition element and a cause of radical ROS formation through Fenton reaction. These ROS radicals cause lipid peroxidation, an end product of MDA. Consistent with our study, Rijkgauer et al [29], analyzed trace elements and MDA concentrations in healthy persons and compared Cu levels and MDA concentrations, and found no correlations between them. Other trace elements (Mg. Fe) have no obvious correlation with SOD and MDA.
According to our results, elevate OS may play a role in the trace elements imbalance in CKD. Dialysis itself seems to have no obvious effect on plasma trace elements concentrations compared with No-dialysis CKD5 patients. Therefore, decreasing sources of oxidative stress and at the same time increasing oxidative capacity can be beneficial to these patients. These findings show that whereas prolonged replacement treatment leads to improved oxidative stress damage, trace element concentrations are not affected. Since both deficiency and excess of trace elements are potentially harmful yet amenable to therapy, the hypothesis that trace element status influences the risk of adverse clinical outcomes is worthy of investigation. And it is critical if micronutrient interventions are to be not only effective, but also targeted to those with the greatest need.