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Table of Contents
Year : 2022  |  Volume : 5  |  Issue : 1  |  Page : 33-36

Serum zinc level in patients on maintenance hemodialysis and its relationship to anemia

1 Department of Pediatrics, Bouali Hospital, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
2 Department of Pediatric Nephrology, Bahrami Children Hospital, Tehran, Iran
3 Pediatric Chronic Kidney Disease Research Center, Department of Pediatric Nephrology, Children Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran

Date of Submission17-May-2021
Date of Decision25-Sep-2021
Date of Acceptance27-Oct-2021
Date of Web Publication28-Jun-2022

Correspondence Address:
Mastaneh Moghtaderi
Department of Pediatric Nephrology, Pediatric Chronic Kidney Disease Research Center, Children Medical Center Hospital, Tehran University of Medical Sciences, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajpn.ajpn_23_21

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Hemodialysis patients are at risk for deficiency or excess of trace elements, both of which can affect their health. Zinc is an essential trace element and its deficiency results in the dysfunction of plasma membrane proteins and enhanced oxidative stress in cells, especially red blood cells, thus decreasing their lifespan. Zinc deficiency is reported in 40%–78% of hemodialysis patients and may be associated with anemia. Both anemia and zinc deficiency are common in patients with kidney failure. In this study, serum zinc levels and their relationship to anemia were evaluated in 24 patients on maintenance hemodialysis for 6 months or longer at either of two tertiary pediatric hemodialysis centers in Tehran, Iran. Serum zinc level and various blood indices were recorded before, during, and after the evaluation over 6 months. Patients receiving zinc-containing supplements in the 3 months before enrolment were ineligible. Patients with zinc deficiency received oral supplements of zinc sulfate at 1 mg/kg daily for 3 months, following which serum zinc level and other blood indices were retested to examine the influence of zinc supplementation on anemia. Our findings indicate that serum zinc levels may correlate with anemia in hemodialysis patients. Providing zinc supplements may improve anemia and the quality of life in patients with low zinc levels.

Keywords: Anemia, chronic kidney disease, kidney failure, micronutrient

How to cite this article:
Ekhlasi N, Mojtahedi Y, Afshin A, Bazargani B, Abbasi A, Askarian F, Fahimi D, Moghtaderi M. Serum zinc level in patients on maintenance hemodialysis and its relationship to anemia. Asian J Pediatr Nephrol 2022;5:33-6

How to cite this URL:
Ekhlasi N, Mojtahedi Y, Afshin A, Bazargani B, Abbasi A, Askarian F, Fahimi D, Moghtaderi M. Serum zinc level in patients on maintenance hemodialysis and its relationship to anemia. Asian J Pediatr Nephrol [serial online] 2022 [cited 2022 Dec 2];5:33-6. Available from: https://www.ajpn-online.org/text.asp?2022/5/1/33/348525

  Introduction Top

Zinc is an essential trace element in human life. It is an essential part of many enzymes, including those involved in hemoglobin synthesis, is the chief regulator of red cell growth, and regulates erythropoiesis. It also plays essential biological roles, including in gene expression, protein synthesis, and immune responses.[1],[2] Increased expression of intracellular metallothionein or oxidative stress during chronic diseases can decrease serum zinc levels.[3] Zinc deficiency is reported in patients with kidney failure and may stem from hypoproteinemia, proteinuria, impaired tubular reabsorption, and deficiency of vitamin D, which has an important role in the intestinal absorption of zinc.[2] Patients on maintenance hemodialysis are exposed to large amounts of highly purified dialysis solution repeatedly, which removes zinc, iron, selenium, and other essential trace elements, resulting in clinically relevant micronutrient deficiencies.[4] These patients are also at risk of reduced dietary intake of these micronutrients due to uremia-related anorexia and dietary restrictions, as well as frequent changes in their metabolism.[1] In addition, patients with kidney failure may have decreased intestinal absorption or excess fecal excretion of trace elements including zinc.[5] Since zinc is less reactive than sodium, it does not react with sodium bicarbonate and presumably crosses the dialysis membranes by diffusion from serum into dialysate; hence, the dialysate bicarbonate concentration does not affect serum zinc during hemodialysis.[2],[5] Zinc supplementation in patients on maintenance hemodialysis is known to increase hemoglobin levels even in those without apparent zinc deficiency.

This study was designed to estimate serum zinc concentration in patients undergoing maintenance hemodialysis to find potential correlations between serum zinc level and the presence of anemia before and following zinc supplementation.

  Materials and Methods Top

This study was conducted as part of a fellowship project that was approved by the Research and Institutional Ethics Committees (IR.TUMS.CHMC.REC.1399.055) of the Tehran University of Medical Science. Details of the study were explained to the participants and their parents followed by their written consent before enrolment in the study. Patients on maintenance hemodialysis were enrolled at two referral centers from February to December 2019. Patients were eligible if they were on maintenance hemodialysis for kidney failure for at least 6 months. Exclusion criteria were the presence of malignancy or chronic infection and the use of zinc-containing supplements or peritoneal dialysis. Use of supplements containing iron (2–6 mg/kg daily), folic acid (1 mg daily when required), erythropoietin (50–150 IU/kg weekly), and supplements containing essential vitamins was permitted, but no use of zinc supplements, for the past 3 months and during the study period. The doses of these medications, the duration and frequency of hemodialysis sessions, and the size and type of dialyzers used were not altered during the study.

Serum levels of zinc and blood indices were checked in these patients using 5 mL of predialysis blood samples collected in acid-washed tubes and centrifuged at 3000 rpm for 10 min. The serum was separated and frozen at −20°C until analysis for serum zinc levels using a GBC 932 atomic absorption spectrophotometer (GBC Scientific Pty Ltd., Melbourne, Australia). Each sample was checked twice at 213.9 nm wavelength. Peak high measurements were compared with values for standards of known concentrations made up in serum. Zinc deficiency was defined as serum zinc concentration of <70 μg/dL, as recommended previously.[6] Complete blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, red blood cell count, serum iron, total iron-binding capacity (TIBC), ferritin, albumin, acute phase C-reactive protein, and serum electrolytes were measured in all patients. Transferrin saturation (TSAT) was calculated by the following formula: TSAT = serum iron × 100/TIBC.

Patients with serum zinc levels lower than 70 μg/dL received 1 mg/kg (maximum 50 mg) of zinc sulfate daily orally. Hemoglobin, other blood indices, and serum zinc levels were evaluated monthly in the next 3 months. Collected data were analyzed using the SPSS software version 23 (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp. IBM Corp. Released 2016). For data that were normally distributed, as assessed by Kolmogorov Smirnov test, the correlation between continuous variables was assessed using the Pearson correlation test. Statistical significance was assigned at P < 0.05.

  Results Top

Twenty-four patients (50% boys) were enrolled. The mean ± standard deviation age was 15.1±3.6 years, and the majority of patients were between 10 and 15 years old. The mean duration of hemodialysis was 4.7±3.9 years (maximum 11 years), but the mean duration from the establishment of kidney failure was 9.4±3.5 years. Fifteen (62.5%) patients had low serum zinc levels (serum zinc <70 μg/dL). Patients with zinc deficiency were older (11.4±6.4 years vs. 10.3±4.9 years; P = 0.025) and had longer duration on dialysis (5.7±3.7 years vs. 3.1±3.7 years) than the zinc-sufficient patients.

[Table 1] demonstrates serum levels of parameters at the beginning and end of the study in both groups. Serum zinc levels were 66.1±9.2 μg/dL in the zinc-deficient group and 95.2±22.6 μg/dL in the zinc-sufficient group. Levels of hemoglobin, hematocrit, and MCV improved significantly from baseline to the end of the study in the zinc-supplemented group [from 10.8±1.9 g/dL, 35.7±12.9 and 92.5±7.9 fL, respectively, before supplementation to 12.2±2.2 g/dL, 39.3±2.7 and 98.0±14.8 fL, respectively, after zinc supplementation; [Figure 1]]. The level of serum ferritin was higher in patients with zinc deficiency and decreased after zinc supplementation, from 1020.9±867.2 ng/mL to 970.5±775.9 ng/mL.
Table 1: Serum levels before and following 3 months of zinc supplementation

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Figure 1: Mean values of hemoglobin (g/dL), hematocrit, and mean corpuscular volume (fL) during the study in the group of patients receiving zinc supplementation

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  Discussion Top

The management of refractory anemia in patients with kidney failure is challenging. Anemia in patients with kidney failure is associated with cardiovascular mortality and morbidity, while correction of anemia is linked to improvement in quality of life.[7]

This present study suggests an association between serum zinc levels and the presence of anemia in patients on hemodialysis. An inverse correlation of serum zinc level with age was previously demonstrated for patients on hemodialysis as well as peritoneal dialysis.[8] However, we found zinc deficiency to be more prevalent in younger patients. Neither we nor others found any differences in the levels of zinc and hemoglobin between boys and girls.[8],[9],[10]

Supplementation of zinc led to improvement in anemia and quality of life in patients with zinc deficiency. These findings are similar to those of Fukushima et al. who reported that serum levels of zinc correlate with all parameters indicating anemia and that patients with higher zinc levels show better improvement in anemia and zinc supplementation reduces erythropoietin requirement.[9] Dashti-Khavidaki et al. showed that the levels of zinc and hemoglobin were significantly lower in patients' refractory to erythropoietin as compared to those responsive to erythropoietin.[8] In our study, patients receiving zinc supplements showed improvement in levels of hemoglobin and red cells indices and reduced the need for erythropoietin.

Serum levels of zinc should be monitored periodically in patients on hemodialysis. Deficient patients may benefit from zinc supplementation, with correction of anemia. Future studies should examine the utility of routine zinc supplementation in all patients on hemodialysis.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Tonelli M, Wiebe N, Hemmelgarn B, Klarenbach S, Field C, Manns B, et al. Trace elements in hemodialysis patients: A systematic review and meta-analysis. BMC Med 2009;7:25.  Back to cited text no. 1
Cabral PC, Diniz Ada S, de Arruda IK. Vitamin A and zinc status in patients on maintenance haemodialysis. Nephrology (Carlton) 2005;10:459-63.  Back to cited text no. 2
Bozalioğlu S, Ozkan Y, Turan M, Simşek B. Prevalence of zinc deficiency and immune response in short-term hemodialysis. J Trace Elem Med Biol 2005;18:243-9.  Back to cited text no. 3
Lönnerdal B. Dietary factors influencing zinc absorption. J Nutr 2000;130:1378S-83S.  Back to cited text no. 4
Dvornik S, Cuk M, Racki S, Zaputović L. Serum zinc concentrations in the maintenance hemodialysis patients. Coll Antropol 2006;30:125-9.  Back to cited text no. 5
Gibson RS. Principals of Nutrition Assessment. New York: Oxford University Press; 1990. p. 542-53.  Back to cited text no. 6
Mariak I, Grzegorzewska AE. Serum zinc concentration with reference to other markers of continuous ambulatory peritoneal dialysis patients status. Pol Merkur Lekarski 2002;12:282-7.  Back to cited text no. 7
Dashti-Khavidaki S, Khalili H, Vahedi SM, Lessan-Pezeshki M. Serum zinc concentrations in patients on maintenance hemodialysis and its relationship with anemia, parathyroid hormone concentrations and pruritus severity. Saudi J Kidney Dis Transpl 2010;21:641-5.  Back to cited text no. 8
[PUBMED]  [Full text]  
Fukushima T, Horike H, Fujiki S, Kitada S, Sasaki T, Kashihara N. Zinc deficiency anemia and effects of zinc therapy in maintenance hemodialysis patients. Ther Apher Dial 2009;13:213-9.  Back to cited text no. 9
Elbadri A, Kheiri I, Abdalla AM. Evaluation of serum zinc level in Sudanese patients of erythropoietin resistant in hemodialysis. Health Sci J 2018;12:613.  Back to cited text no. 10


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