Zinc and haemodialysis
Zn concentration has been accepted as a valid indicator of whole-body Zn in the absence of influencing factors such as infection or stress [11]. Zn deficiency in HD patients has a prevalence of 40–78% [12]. Only 1 out of 61 (1.6%) included dialysis patients had zinc deficiency in our study. An association between low serum Zn level and multiple protein energy malnutrition (PEM) parameters was proposed, which can predict poor clinical outcomes in chronic HD patients [12]. Low serum Zn concentrations could be a consequence of Zn removal by dialysis, low levels of albumin, and reduced absorption of Zn by gastrointestinal tract [2]. What is more, inflammation processes can reduce the plasma Zn levels [2]. Older HD patients had lower serum Zn levels than younger, however, a direct correlation between age and Zn level was not found [13]. In patients on peritoneal dialysis, Zn had a positive correlation with serum prealbumin level [13]. The same was shown in HD patients [12].
However, Zn deficiency was not present in our group of HD patients that can be explained by the fact that more than 40% of our patients used ONS continuously and independently from Zn values.
Zinc and inflammation
Fifteen randomized controlled trials meta-analysis showed that supplementing Zn had anti-inflammatory and antioxidant effects in chronic HD patients [3]. The antioxidant activity of Zn involves two mechanisms connected with sulfhydryl and metallothionein [3]. Zn could also decrease CRP and other inflammatory cytokines by increased antioxidant activity, the major target is most likely the NF-kappa B-related signalling pathway [3]. It was found that Zn supplementation decreased the level of CRP in dialysis patients [14].
In our study no statistically significant difference in CRP values between the patients that had serum Zn level above or below the median value was found.
Zinc and atherosclerosis
The progression of atherosclerosis is influenced by nutritional parameters including Zn. Zn deficiency could contribute to atherosclerotic process and there was an inverse relationship between atherosclerosis and serum Zn levels [4]. In the study conducted by Yang et al. the subclinical atherosclerosis was determined by using carotid intima-media thickness (cIMT) and analysed its relationship with the dietary Zn intake. In the middle-aged and elderly, lower Zn intake was associated with a higher cIMT than the higher Zn intake [15]. Ari et al. proposed that the copper/Zn ratio is an independent determinant of cIMT in chronic HD patients without known atherosclerosis. A negative correlation between cIMT and serum levels of Zn was found [16].
Despite the fact that ABI is known as a marker of atherosclerosis in haemodialysis patients [17], there is no study relating Zn and ABI in haemodialysis patients to our knowledge.
In our study, lower ABI was associated with lower Zn levels. Since lower ABI is a marker of atherosclerosis, it appears that in our patients lower Zn values relate to a higher risk of atherosclerosis.
Zinc and lipids
Although studies suggested that Zn supplementation improves blood lipid metabolism, the effects of Zn supplementation are conflicting with several possible reasons mentioned [3, 12]. Zn supplementation could increase blood lipids in patients with anorexia and have an opposite effect in patients with hyperlipidaemia or insulin resistance [3]. Hypercholesterolemia and hypertriglyceridemia have been observed in patients with Zn-deficient diets, which could lead to cardiovascular complications and insulin resistance in CKD patients [3]. A positive correlation between Zn and serum total cholesterol concentrations in the malnourished HD patients has been shown [10]. A higher mortality of HD patients was found with predialysis cholesterol levels below 3.88 mmol/l [12]. Since HD patients are often Zn-deficient, Zn supplementation may also increase abnormally low serum lipid concentrations, connected with malnutrition and morbidity in the HD patients [12].
However, in our study the mortality was higher in the group of patients with serum Zn above the median value, and this group also had a higher total cholesterol level (although not statistically significant). The group of patients with lower Zn level had serum total cholesterol slightly above the minimum value for the above-mentioned increased mortality and the group of the patients with higher Zn level had normal total cholesterol.
Zinc and mortality
The study of Yang et al. included 111 patients on maintenance HD, which were followed for 2 years or until their death. The authors concluded that in chronic dialysis patients, the serum level of Zn was an independent predictor of hospitalisations caused by infectious diseases and of all-cause mortality. They found that lower serum level of Zn independently predicts all-cause mortality, the mean serum value of Zn in the study was in the range of low normal [18]. In the study of Lobo et al., HD patients had low serum Zn levels, and high LDL and TNF-alpha levels compared to healthy subjects. Serum Zn levels correlated negatively with TNF-alpha and LDL, low Zn levels were associated with lipid peroxidation and inflammation and the inflammation markers were significant predictors of cardiovascular mortality [19]. Most above-mentioned studies are dealing with malnutrition, the lack of Zn and consequently higher mortality.
In our study, patients were already taking ONS that included Zn. Patients with higher levels of serum Zn had a higher risk of death, which was not statistically significant, however, our mean value of Zn was in normal range. Patients with higher Zn level had statistically significantly higher level of serum albumin, the percentage of patients taking ONS in this group was higher, however, the difference was not statistically significant. The difference in BMI between the two groups was not statistically significant. We propose that the decreased survival of patients with higher Zn values and ONS supplementation was not directly affected by these two parameters but was only a marker of previous malnourishment and generally worse condition of these patients (since the criteria for prescription was serum albumin level below 40 g/l). However, due to the retrospective design of the study, this is only a possible explanation and therefore further prospective research should be conducted to draw definitive conclusions.
Study limitations
A small number of patients is a limitation to our study. Only Caucasian patients were included.
Substitution volume differences during HDF between the patients which could have had an effect on serum Zn level were not considered. We also did not factor in different high-flux membranes between patients and their individual properties, especially regarding micro-trace elements removal. The history of ONS consumption should have also been considered.