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Original Article

Serum trace elements before and 3 months afterrenal transplantation in kidney recipients: AnIranian study

Mohammad Reza Nikoobakht, Gholamreza Pourmand, Farzad Allameh,Hossein Dialameh*, Amirsina Sharifi, Arsalan Hashemiaghdam

Urology Research Center, Sina Hospital, Tehran, Iran

a r t i c l e i n f o

Article history:

Received 21 September 2013

Accepted 3 December 2013

Available online 22 December 2013

Keywords:

Renal transplantation

trace elements

Creatinine

* Corresponding author. Tel.: þ98 9173174014E-mail address: hossein.dialameh@gmail

2212-0017/$ e see front matter Copyright ªhttp://dx.doi.org/10.1016/j.ijt.2013.12.002

a b s t r a c t

Background: Decreased serum levels of trace elements seen in long-term hemodialysied

patients, suppress immune system. The aim of this study was to find if any changes occur

in trace elements after transplantation and assess the correlation between post-

transplantation renal function and levels of trace elements.

Methods: Long-term hemodialysied patients with underlying ESRD were divided into two

groups, who were undergone transplantation (n ¼ 54) and were not (n ¼ 69). Levels of

lithium, magnesium, iron, zinc and copper measured 24 h before and three months after

transplantation in both groups. The transplanted patients’ serum levels of creatinine were

assessed at same intervals as an indicator of graft function.

Results: 54 patients, 18 men (33%), 36 women (67%) with mean age of 47.67 � 14.33 years

underwent transplantation between April 2010 and April 2011. While serum iron (p < 0.001)

and copper levels (p < 0.001) significantly increased after transplantation, there was a

statistically significant reduction in magnesium levels (p < 0.001) .No significant differences

were noted in zinc (p ¼ 0.17) and lithium (p ¼ 0.080) levels in comparison to control group .A

significant relationship was noted between levels of magnesium (p ¼ 0.015) and zinc

(p ¼ 0.025) and creatinine within three months after transplantation.

Conclusion: Our study showed transplantation alters serum levels of trace elements in long-

term hemodialysied patients with underlying ESRD and affects immunity and the results of

renal function (Cr levels).

Copyright ª 2013, Indian Society of Organ Transplantation. All rights reserved.

1. Introduction

Patients with end-stage renal disease (ESRD) and long-term

hemodialysis are at high risk for several disorders.1,2 This is

because of factors like long time dialysis, poor nutritional

(mobile); fax: þ98 21663.com (H. Dialameh).2013, Indian Society of O

status, oxidative stress, inflammation and infection affecting

their immune system, making them more vulnerable.3e6

Decreased serum albumin levels and increased oxidative

stress in these patients are due to poor nutrition and altered

serum levels of essential trace elements.7,8 Metabolic disor-

ders in patients with ESRD can also alter the serum

48500.

rgan Transplantation. All rights reserved.

Table 1 e Serum levels of trace elements before and three

i n d i a n j o u rn a l o f t r a n s p l a n t a t i o n 8 ( 2 0 1 4 ) 8e1 1 9

concentrations of trace elements. On the other hand, changes

in trace elements can be secondary to their disrupted gastro-

intestinal tract function, proteinuria, consumed medications

and the presence of other comorbidities such as diabetes.9e11

Efficient immune system function is related to appropriate

intake of trace elements. Decreased serum levels of trace el-

ements suppress immune system by affecting innate, T cell

mediated and adaptive antibody responses, which is leading

to alter host immune response. It can raise mortality and

morbidity by increasing the chance of infection. On the other

hand infection can worsen serum levels of trace elements by

reduction in trace elements intake, increase in losses via GI

tract and changes in metabolic pathways which is leading to

misusage of trace elements. Trace elements enhance body’s

natural defense in three ways by supporting cellular immu-

nity, physical barriers (skin/mucosa), and antibody produc-

tion. For example zinc enhances skin barrier function and

zinc, iron, selenium and copper work in synergy to advance

the immune cells function. All these trace elements are

needed to antibody production.12 Long-term dialysis is linked

to increased oxidative stress and reduced zinc (Zn) levels.13

This is while Zn, because of its antioxidant and anti-

inflammatory properties, can help reduce inflammation in

dialysis patients.14,15 Copper (Cu), a co-factor of ceruloplasmin

and superoxide dismutase (SOD), is also reported to play an

important role in the synthesis of hemoglobin and having a

healthy immune system.16,17 Some studies have indicated

that uremic patients have lower selenium levels than healthy

individuals.18,19 This is mainly because uremic patients who

underwent chronic dialysis lose trace elements through dial-

ysis membrane.20

The aim of this study was to investigate changes in serum

levels of trace elements after transplantation and determine

its effects on post-transplantation renal function by evalua-

tion of creatinine levels.

months after kidney transplantation.

Beforetransplantation(mean � SD)

3 Months aftertransplantation(mean � SD)

p-value*

Lithium (mmol/L) 0.43 � 0.27 0.53 � 0.44 0.080

Magnesium

(mmol/L)

2.30 � 0.30 1.87 � 0.34 <0.001

Iron (mg/dL) 66.85 � 33.49 90.85 � 29.60 <0.001

Zinc (mg/dL) 110.87 � 38.12 99.48 � 34.40 0.170

Copper (mg/L) 100.92 � 20.69 124.07 � 19.28 <0.001

*p < 0.05 ¼ significant.

Table 2 e Post-transplantation serum levels of traceelements in transplanted patients based on theircreatinine levels.

Cr < 1.4(mean � SD)

Cr � 1.4(mean � SD)

p-value*

Lithium (mmol/L) 0.60 � 0.292 0.46 � 0.34 0.095

Magnesium (mmol/L) 1.78 � 0.32 1.96 � 0.33 0.015*

Iron (mg/dL) 93.00 � 33.78 88.85 � 25.59 0.615

Zinc (mg/dL) 102.23 � 34.95 96.92 � 34.32 0.025*

Copper (mg/L) 123.92 � 15.89 124.21 � 22.26 0.955

*p < 0.05 ¼ significant.

2. Methods

This descriptive prospective study was conducted between

April 2010 and April 2011 on two groups of patients. Group one

were all consecutive ESRD patients (of any etiology) who un-

derwent kidney transplantation from a living donor in our

hospital and group two were ESRD patients with history of

chronic hemodialysis who have not kidney transplantation as

control group. The study was approved by the Ethical Board

Committee of Tehran University of Medical Sciences. All the

patients signed an informed consent before being enrolled

into the study.

The required blood samples were collected from all pa-

tients, 24 h before transplantation, to measure serum levels of

lithium, magnesium, iron, zinc and copper. Three months

after the transplantation, the patient’s serum creatinine level

and kidney function were evaluated. Also blood samples of

patients in control group were taken during three months

period.

The data were analyzed using descriptive statistics anal-

ysis (chi-square, Paired T-Test, Spearman correlation) in

Microsoft SPSS version 20.

Baseline creatinine levels as high as 1.4 were set as the cut

point to divided transplanted patients into two groups. This

amount of creatinine was selected because it is the upper

normal limit of creatinine in healthy individuals which could

help to compare renal functional changes after trans-

plantation to normal population.

3. Results

During the study period, 44 patients (18males and 26 females)

with ESRD who received kidney transplants from a living

donor were recruited. Their mean age was 47.67� 14.33 years,

ranging from 32 to 62 years old. The control group was 69

patients consist of 24 males and 45 females and their mean

age was 35.12 � 15.22 years, ranging from 19 to 51. Mean

serum levels of the trace elements in the beginning of the

study and within post-transplantation period are outlined in

Table 1. Findings revealed a significant reduction in magne-

sium levels after the transplantation (p < 0.001). There was

significant increase in iron and copper after the trans-

plantation (p < 0.001 and p < 0.001, respectively). But for zinc

and lithium reported increase was not statistically significant

(p > 0.05). Mean creatinine levels was 1.4 � 0.46 mg/dL. Based

on their creatinine levels, 26 (48%) were categorized in group 1

(Cr � 1.4) and the other 18 in group 2 (Cr > 1.4).

While serum levels of Li, Fe and Zn were higher in the

group 1; there was no significant difference in this regard

(Table 2). There was a significant correlation between post-

transplantation Cr levels and serum levels of and Mg (p-

value ¼ 0.015, r: 0.355). On the other hand, an inverse and

Table 3 e Serum levels of trace elements in ESRD patientswith history of hemodialysis that did not have kidneytransplantation in three months period.

Baselineserum level

After threemonths period

p-value*

Lithium (mmol/L) 0.44 � 0.35 0.43 � 0.29 p < 0.0185

Magnesium (mmol/L) 2.33 � 0.32 2.280.25 p < 0.070

Iron (mg/dL) 65.9 � 32.8 66.2 � 33.5 p < 0.085

Zinc (mg/dL) 109.9 � 37.2 107.8 � 36.9 p < 0.065

Copper (mg/L) 101.2 � 19.3 104 � 19.8 p < 0.080

*p < 0.05 ¼ significant.

i n d i a n j o u r n a l o f t r an s p l a n t a t i o n 8 ( 2 0 1 4 ) 8e1 110

significant correlation was reported between Zn and these

patients’ creatinine levels (p-value ¼ 0.025, r: 0.362).

In control group all trace elements show no significant

changes during three months period (Table 3).

4. Discussion

Trace elements have recently become a matter of great in-

terest and altered serum levels of elements such as antimony,

arsenic, cadmium, molybdenum, nickel, and selenium have

been reported in ESRD patients who treated with hemodialy-

sis for long-term period,21,22 but there is no reports for trace

element alteration in transplant patients. It is believed that

following kidney transplantation, there would be a normal-

ized renal function, and thus serum levels of different ele-

ments would become close to normal values. The results of

the present study showed a significant increase in Fe and Cu

levels after kidney transplantation. Mg levels, on the other

hand, reduced after the operations and lithium and zinc levels

show no significant changes during three months period.

While post-transplantation Zn levels were significantly

correlated with Cr, an inverse correlation was reported for Mg.

In line with our findings, a Turkish study concluded that long-

term dialysis can increase oxidative damage, but has no effect

on the concentration of trace elements.23

Zachara et al studied selenium and glutathione peroxidase

concentrations in blood samples of patients before and after

renal transplantation. They reported a significant increase in

selenium levels of these patients within three months after

transplantation.24 Chen et al, in 2009 similarly measured

serum levels of selenium, lead and cadmium in Chronic Renal

Failure (CRF) and long-term hemodialysis patients and

compared the results with that of a group with normal renal

function. The results showed that patients with renal failure

had significantly lower selenium serum levels than normal

individuals. While the patients with renal failure were also

reported to have higher content of cadmium, there was no

such difference in lead levels.18 Findings from Kiziltas et al’s

study showed lower albumin and zinc (Zn) levels after dialysis,

while their Mg contentwas higher than the healthy subjects.25

5. Limitation

Considering the cross-sectional nature of the study, causal

inferences cannot bemade.Moreover, the present study failed

to assess all the factors that could have influenced the renal

function after the transplant, including the underlying cause

of renal failure in the patients, the comorbid diseases and the

duration of dialysis before the transplant. Further studies on

larger sample size are therefore needed to take all these fac-

tors into consideration.

6. Conclusion

The present study showed that transplantation can alter

serum levels of trace elements in ESRD patients whit history

of long-term hemodialysis. Considering the importance of

trace elements in improving immune system function and

prevention of infections which can affect the transplantation

acute and chronic results it is needed to observe their serum

levels after transplantation and correct them to normal ranges

which can lead to more efficient transplantations. Thus

monitoring of trace elements after renal transplantation in

order to improve immune system efficacy is needed.

Conflicts of interest

All authors have none to declare.

r e f e r e n c e s

1. US Renal Data System. USRDS. Annual Data Report: Atlas ofChronic Kidney Disease and End-stage Renal Disease in the UnitedStates. Bethesda, MD: National Institutes of Health, NationalInstitute of Diabetes and Digestive and Kidney Diseases; 2008.

2. Rees L. Long-term peritoneal dialysis in infants. Periton DialInt. 2007;27:s180es184.

3. Dounousi E, Papavasiliou E, Makedou A, et al. Oxidative stressis progressively enhanced with advancing stages of CKD. Am JKidney Dis. 2006;48:752e760.

4. Himmelfarb J. Oxidative stress in hemodialysis. ContribNephrol. 2008;161:132e137.

5. Karamouzis I, Sarafidis PA, Karamouzis M, et al. Increase inoxidative stress but not in antioxidant capacity withadvancing stages of chronic kidney disease. Am J Nephrol.2008;28:397e404.

6. Sundl I, Roob JM, Meinitzer A, et al. Antioxidant status ofpatients on peritoneal dialysis: associations withinflammation and glycoxidative stress. Periton Dial Int.2009;29:89e101.

7. Lee EJ, Myint CC, Tay ME, Yusuf N, Ong CN. Serum ascorbicacid and protein calorie malnutrition in continuousambulatory peritoneal dialysis patients. Adv Perit Dial.2001;17:219e222.

8. Guo CH, Ko WS, Chen PC, Hsu GSW, Lin CY, Wang CL.Alterations of trace elements and oxidative stress in uremicpatients with dementia. Biol Trace Elem Res. 2009;131:13e24.

9. Bjarnason NH, Munkner R, Kampmann JP, et al. Optimizinglithium dosing in hemodialysis. Ther Drug Monit.2006;28(2):262e266.

10. Wills MR. Effects of renal failure. Clin Biochem. 1990;23:55e60.11. Bozalio�g lu S, O00 zkan Y, Turan M, Sqims‚ek B. Prevalence of

zinc deficiency and immune response in short-termhemodialysis. J Trace Elem Med Biol. 2005;18:243e249.

i n d i a n j o u rn a l o f t r a n s p l a n t a t i o n 8 ( 2 0 1 4 ) 8e1 1 11

12. Maggini S, Wintergerst ES, Beveridge S, Hornig DH. Selectedvitamins and trace elements support immune function bystrengthening epithelial barriers and cellular and humoralimmune responses. Br J Nutr. 2007;98(suppl 1):S29eS35.

13. Roozbeh J, Hedayati P, Sagheb MM, et al. Effect of zincsupplementation on triglyceride, cholesterol, LDL, and HDLlevels in zinc-deficient hemodialysis patients. Ren Fail.2009;31:798e801.

14. Rashidi AA, Salehi M, Piroozmand A, Sagheb MM. Effects ofzinc supplementation on serum zinc and C-reactive proteinconcentrations in hemodialysis patients. J Ren Nutr.2009;19:475e478.

15. Munguıa C, Paniagua R, Avila-DıazM,Nava-Hernandez J,Rodrıguez E, VenturaMde J, et al. Effect of zinc supplementson the nutritional status of patients undergoing continuousambulatory peritoneal dialysis. Rev Invest Clin.2003;55:519e527.

16. Sahin H, Uyanik F, Inanc N, Erdem O. Serum zinc,plasmaghrelin, leptin levels, selected biochemical parametersand nutritional status in malnourished hemodialysispatients. Biol Trace Elem Res. 2009;127:191e199.

17. Matson A, Wright M, Oliver A, et al. Zinc supplementation atconventional doses does not improve the disturbance of tasteperception in hemodialysis patients. J Ren Nutr.2003;13:224e228.

18. Chen B, Lamberts LV, Behets GJ, et al. Selenium, lead, andcadmium levels in renal failure patients in China. Biol TraceElem Res. 2009;131(1):1e12.

19. Zagrodzki P, Barto�n H, Walas S, et al. Selenium status indices,laboratory data, and selected biochemical parameters in end-stage renal disease patients. Biol Trace Elem Res.2007;116(1):29e41.

20. Hoenich NA, Levin R, Ronco C. How do changes in waterquality and dialysate composition affect clinical outcomes?Blood Purif. 2009;27(1):11e15.

21. Covic A, Gusbeth-Tatomir P. Trace elements in end-stagerenal disease e unfamiliar territory to be revealed. BMCNephrology. 2009;10:12.

22. Tonelli M, et al. Trace elements in hemodialysis patients: asystematic review andmeta-analysis. BMCMedicine. 2009;7:25.

23. Koca T, Berber A, Koca HB, et al. Effects of hemodialysisperiod on levels of blood trace elements and oxidative stress.Clin Exp Nephrol. 2010;14:463e468.

24. Zachara BA, Włodarczyk Z, Masztalerz M, et al. Seleniumconcentrations and glutathione peroxidase activities in bloodof patients before and after allogenic kidney transplantation.Biol Trace Elem Res. 2004 Jan;97(1):1e13.

25. Kiziltas H, Ekin S, Erkoc R. Trace element status of chronicrenal patients undergoing hemodialysis. Biol Trace Elem Res.2008 Aug;124(2):103e109.