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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 4  |  Page : 641-645
Serum zinc concentrations in patients on maintenance hemodialysis and its relationship with anemia, parathyroid hormone concentrations and pruritus severity


1 Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Nephrology and Dialysis, Imam Referral Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Date of Web Publication26-Jun-2010
 

   Abstract 

Zinc (Zn) deficiency has been reported in 40-78% of hemodialysis (HD) patients and may be associated with anemia and pruritus and probably limiting the expression of renal osteodystrophy. This study was designed to explore possible correlation between serum zinc concentration and anemia, intact parathyroid hormone (iPTH) concentration and pruritus severity in HD patients. During a case-control study, the serum Zn concentration of patients on main­tenance HD was compared with those of the healthy controls and with the cut-off point of 70 mcg/dL as the risk of Zn deficiency. The mean serum Zn concentration in patients on main­tenance HD was significantly lower than that of the control group; however, it was not different with the cut-off point of 70 μg/dL. No correlation between serum Zn concentration and hema­tologic indices was detected. A significant positive correlation between serum Zn concentration and erythropoietn dose was noted. No correlation was found between serum Zn concentration and PTH level or pruritus severity. In conclusion the results of this study showed that zinc concentrations were lower in HD patients compared to controls, however, the effects of routine supplementation of zinc to control anemia, serum PTH level or pruritus severity are yet doubtful.

How to cite this article:
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

How to cite this URL:
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 [serial online] 2010 [cited 2019 Jul 20];21:641-5. Available from: http://www.sjkdt.org/text.asp?2010/21/4/641/64620

   Introduction Top


Trace element deficiencies (more commonly for zinc (Zn), iron and possibly selenium) occur in hemodialysis (HD) patients. [1] Trace element metabolism change frequently in patients with Chronic Kidney Disease (CKD) who undergo HD. [2] Zinc deficiency in CKD patients may be due to fecal excretion or decrease in its ab­sorption. [3] Zn deficiency may be associated with some of the uremic symptoms such as ano­rexia, hypogeusia, sexual dysfunction or de­creased immunologic function. [2]

Animal research showed depressed hemato­poiesis due to low plasma erythropoietin (EPO) concentration in Zn deficient rats. [4] In another renal ablation model producing uremia in rats, parathyroid hormone (PTH) increase was limi­ted with the presence of Zn deficiency. [5]

Some authors proposed Zn deficiency as a possible cause of histamine release and the de­velopment of uremic pruritus in HD patients. [6]

This study was designed to assess the serum Zn concentration in patients undergoing main­tenance HD and to find any possible corre­lation between serum zinc concentration and anemia, PTH concentration and pruritus seve­rity. The relation between serum Zn concen­tration and co-medications, preliminary disor­ders leading to CKD and other biochemical indices of the patients were evaluated as se­condary endpoints.


   Materials and Methods Top


During a cross-sectional, case-control study, the serum Zn concentration of patients on maintenance HD was compared with those of the control group. Case group consisted of pa­tients who were undergoing HD three times per week for four hours in each session using acetate buffer, single use polysulfone mem­brane, for more than three months. Control group included healthy volunteers who were matched in age and sex with the case group and did not use any supplementary Zn products or were not on severe weight reducing diet.

The study protocol was approved by the local ethics committee and all patients provided informed consent.

Five milliliters of pre dialysis blood samples were collected in acid-washed tubes and centri­fuged at 3000 r.p.m for ten minutes. The serum was frozen at -20° C until analysis. Serum Zn levels were measured using a GBC 932 atomic absorption spectrophotometer (GBC Scientific Pty Ltd, Melbourne, Australia). Each sample was read twice at 213.9 nm wave-length. Peak high measurements were compared with values for standards of known concentrations made up in serum. Serum Zn concentration of HD patients were also compared with the cut-off point of 70 μg/dL for analyzing the risk of Zn deficiency, as recommended by Gibson. [7]

Demographic characteristics of patients and their baseline disease and medications were recorded. Complete blood count including: he­moglobin (Hgb), hematocrit (Hct), mean cor­puscular hemoglobin concentration (MCHC), red blood cell (RBC) count, serum iron, total iron binding capacity (TIBC), ferritin, albumin (Alb), C-reactive protein (CRP), intact parathy­roid hormone (iPTH), serum electrolytes, total and direct bilirubin and alkaline phosphatase (AlkP) were measured for all patients. Trans­ferin saturation (TSAT) was calculated for each patient by following formula:

TSAT= serum ironΧ100/TIBC

Pruritus severity was assessed using Pauli-­Magnus method [8] for each patient as well.

Data was analyzed using SPSS version 11.5. Due to normal distribution of variables accor­ding to Kolmogorov-Smirnov normal distribu­tion test, independent sample student t-test and one-sample t-test was used to compare serum zinc concentration of HD patients with that of the control group and cut-off point of 70 μg/dL respectively. The correlation between zinc and other laboratory parameters was assessed by Pearson correlation test. One way ANOVA test was used to compare serum Zn concentrations in patients with different underlying disease leading to CKD. Statistical significant level of difference was considered at P< 0.05.


   Results Top


As shown in [Table 1], ninety-four cases (60 males and 34 females) with the mean age of 52.90 ± 18.28 years old and 47 controls (26 males and 21 females) with the mean age of 46.70 ± 18.28 years old completed the study. The mean serum Zn concentration in patients on maintenance HD was significantly lower than that of the control group (69.16 ± 17.29 μg/dL vs 82.93 ± 14.75 μ/dL; P= 0.001); how­ever, it was not different with the cut-off point of 70 μ/dL that is recommended by Gibson [7] (P= 0.66).

The results of this study showed zinc defi­ciency (serum Zn concentration of less than 70 μ/dL) in 57.83% of the HD patients. [Table 2] shows relationship between serum Zn concen­tration and demographic characteristic of HD patients.

[Table 3] shows no correlation between serum Zn concentration and laboratory parameters except total bilirubin.

[Table 4] again shows no significant correlation comparing the mean of serum Zn concentra­tion in patients who were using Calcium car­bonate, Sevelamer, Intravenous iron, Calcitriol, or Erythropoietin with those who did not.

However, a significant positive correlation bet­ween serum Zn concentration and EPO daily dose was noted (r=0.24, P= 0.03).


   Discussion Top


Our study did not find any significant corre­lation between the serum Zn levels and clinical and laboratory parameters.

Serum Zn deficiency has been reported in CKD patients due to hypoproteinemia, protei­nuria, tubular reabsorption impairment and cal­citriol deficiency which has a role in the intes­tinal absorption of Zn. [9] Normal tissue level of Zn despite serum Zn deficiency may show re­distribution of this ion rather than total body deficiency. [9],[10] In another study platelet and plasma Zn status of HD patients were com­pared with the values of the healthy controls. Their results showed low levels compared to controls and post hemodialysis levels of Zn increase due to hemoconcentration and pos­sibly redistribution of platelet Zn levels during hemodialysis. [11]

Some investigators have proposed neutro­phils and platelets as more reliable indices of short-term changes in Zn status than erythro­cytes due to their short life-span. [12]

Studies have documented inverse correlation of serum Zn levels and age both in hemo­dialysis and peritoneal dialysis patients. [13],[14]

We also noted an inverse correlation between age and serum Zn concentration however it was insignificant, P=0.3. Similar to other studies 58% of patients had Zn deficiency. [15] HD fre­quency and time since initiation of HD did not correlate with the serum Zn levels in our pa­tients in contrast to other reports. [16] Medi­cations frequently used in HD patients such as calcium carbonate, calcitriol, and erythropoie­tin may or may not have any correlation with the serum Zn levels as shown by others. [15],[17] We did not find any correlation with any of the medications used except the dose of EPO was significantly higher in patients with higher se­rum Zn concentration.

It is suggested that Zn deficiency in humans may be associated with anemia and correlation was found between decrease in erythroblasts and degree of Zn deficiency. [18]

Positive correlations between serum Zn con­centration and prealbumin, iron, TSAT, Hgb and MCHC have been shown in subjects on continuous ambulatory peritoneal dialysis. [14]

There is an association between Zn defi­ciency and decline in serum insulin-like growth factor (IGF-1) level. [19] It seems that Zn depleted CKD patients respond to supplementary Zn by increase in IGF-1 level and the latter could augment, at least in part, erythropoiesis. [18]

In another study in pregnant women with anemia, two months of supplementary Zn plus iron showed increase in Hgb concentrations and reticulocyte counts compared to controls. [20] Therefore, it may be proposed to add supple­mentary Zn to the regimen of Zn deficient, CKD patients to help in possible reduction in the dose of erythropoietic agents . [18]

Zinc deficiency may also be a representative of nutritional status. Studies show a positive correlation of Zn with albumin, hematocrit and prealbumin, suggesting better nutritional status as reason of higher Zn levels. [21],[22],[23]

Contrary to our findings, [24] an animal study suggested lower levels of iPTH in Zn defi­cient uremic rats suggesting a role of Zn in renal osteodystrophy that needs further elabo­ration. [5] We also looked at the severity of pru­ritis in HD patients and its correlation with Zn. Although we did not find any correlation bet­ween serum Zn concentration of the patient and their pruritus severity, a Japanese study suggests that Zn deficiency may participate in increase histamine level in HD patients and result in the development of uremic pruritus. Oral Zn sulfate supplementation relieved pru­ritus in 53% of their patients. They explained this finding with the inhibitory effect of Zn on various functions of some cells including mast cells. [6]

In conclusion, the results of this study showed that zinc concentrations were lower in HD pa­tients compared to controls, however, revealed no correlation among serum Zn concentration and anemia, serum PTH concentration or pru­ritus severity in HD patients. Further studies are needed to further elaborate on the Zn defi­ciency and its effects in HD patients.


   Acknowledgements Top


This research had been supported by Tehran University of Medical Sciences grant and there is no conflict of interest. The authors thank Ms. Jahanmardi, RN (Imam Hospital nursing de­partment) for her valuable help.

 
   References Top

1.Kalantar-Zadeh K, kopple JD. Trace metals and vitamins in maintenance dialysis patients. Adv Ren Replace Ther 2003;10(3):170-82.  Back to cited text no. 1      
2.Cabral PC, Diniz AS, Arrruda LK. Vitamin A and zinc status in patients on maintenance haemodialysis. Nephrology 2005;10:459-63.  Back to cited text no. 2      
3.Mahajan SK, Bowersox EM, Rye DL. Factors undergoing abnormal zinc metabolism in uremia. Kidney Int 1989;36(27):S269-73.  Back to cited text no. 3      
4.Konomi A, Yokoi K. Zinc deficiency decrease plasma erythropoietin concentration in rats. Biol Trace Elem Res 2005;107(3):289-92.  Back to cited text no. 4      
5.Kimmel PL, Langman CB, Bognar B, et al. Zinc nutritional status modifies renal osteo­dystrophy in uremic rats. Clin Nephrol 2001; 56(6):445-58.  Back to cited text no. 5      
6.Sanada S, Kuze M, Yoshida O. Beneficial effect of zinc supplementation on pruritus in hemodialysis patients with special reference to changes in serum histamine release. Hinyokika Kiyo 1987;33(12):1955-60.  Back to cited text no. 6      
7.Gibson RS. Principals of nutrition assessment. New York: Oxford University Press. 1990: 542-53.  Back to cited text no. 7      
8.Pauli-Magnus C, Mikus G, Alscher DM, et al. Naltrexone does not relieve uremic pruritus: results of a randomized, double blind, placebo­controlled cross-over study. J Am Soc Nephrol 2000;11:514-9.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Candan F, Gultekin F, Candan F. Effect of vitamin C and zinc on osmotic fragility and lipid peroxidation in zinc-deficient haemodia­lysis patients. Cell Biochem funct 2002;20:95-­8.  Back to cited text no. 9      
10.Mafra D, Cuppari L, Cozzolino SM. Iron and zinc status of patients with chronic renal failure who are not on dialysis. J Ren Nutr 2002;12:38-41.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Iotova P, Ionova D, Kuleva V, Antonov S, Tzacher K, Nachev Ch. Zinc in plasma and platelets in patients on regular haemodialysis. Nephrol Dial Transplant 1997;12(2):370-1.  Back to cited text no. 11      
12.Ruz M, Cavan K, Bettger W, Gibsom RS. Erythrocytes, erythrocyte membranes, neutron­phils and platelets as biopsy materials for the assessment of Zn status in humans. Br J Nutr1992;68:515-27.  Back to cited text no. 12      
13.Bozalioglu S, Ozkan Y, Turan M, Simsek B. Prevalence of zinc deficiency and immune response in short-term hemodialysis. J Trace Elem Med Biol 2005;18(3):243-9.  Back to cited text no. 13      
14.Mariak L, Grzegorzewska AE. Serum zinc concentration with reference to other markers of continuous ambulatory peritoneal dialysis patients status. Pol Merkur Lekarski 2002;12 (70):282-7.  Back to cited text no. 14      
15.Lee SH, Huang JW, Hung KY, et al. Trace Metals' abnormalities in hemodialysis patients: relationship with medications. Artif Organs 2000;24(11):841-4.  Back to cited text no. 15      
16.Locsey L, Papp L. Study of trace elements in patients on haemodialysis. Int Urol Nephrol 1983;15(3):289-95.  Back to cited text no. 16      
17.Skarupskiene I, Kuzminskis V, Abdrachmanovas O, Ryselis S, Smalinskiene A. Zinc and alumi­num concentrations in blood of hemodialysis patients and its impact on the frequency of infections. Medicina (Kaunas) 2005;41(1):65-8.  Back to cited text no. 17      
18.Deicher R, HOrl WH. Hormonal adjutants for the treatment of renal anaemia. Eur J Clin Invest 2005;35(3):75-84.  Back to cited text no. 18      
19.Cossack ZT. Decline in somatomedin-C, insulin-like growth factor-1 with experimen­tally induced zinc deficiency in human subjects. Clin Nutr 1991;10:284-91.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]  
20.Nishiyama S, Kiwaki K, Miyazaki Y, Hasuda T. Zinc and IGF-1 concentrations in pregnant women with anemia before and after supple­mentation with iron and/or zinc. J Am Coll Nutr 1999;18:261-7.  Back to cited text no. 20  [PUBMED]  [FULLTEXT]  
21.Schleicher MM, Dutra de Moura FJ, Torreao Braz Diniz EG, et al. Serum zinc and hormonal profile in male dialysis patients receiving hu­man recombinant erythropoietin. J Bras Patol Med Lab 2005;41(4):245-50.  Back to cited text no. 21      
22.Hosokawa S, Yoshida O. Effect of rHuEPO on protein, Zn, Ni, and Mn in patients undergoing haemodialysis. Int Urol Nephrol 1995;27(2): 207-14.  Back to cited text no. 22      
23.Grzegorzewska AE, Mariak I. Zinc as a marker of nutrition in continuous ambulatory peri­toneal dialysis patients. Adv Perit Dial 2001; 17(1):223-9.  Back to cited text no. 23      
24.Navarro-Alarcon M, Reyers-Perez A, Lopez­Garcia H, Palomares-Bayo M, Olalla-Herrera M, Lopez-Martinez MC. Longitudinal study of serum zinc and copper levels in hemodialysis patients and their relation to biochemical mar­kers. Biol Trace Elem Res 2006;113(3):209-22.  Back to cited text no. 24      

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Correspondence Address:
Simin Dashti-Khavidaki
Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran
Iran
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PMID: 20587866

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

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