- Email: [email protected]
Trace elements in renal disease and hemodialysis
Nuclear Instruments and Methods in Physics Research B 189 (2002) 443–449 www.elsevier.com/locate/nimb
Trace elements in renal disease and hemodialysis Yoshinori Miura a b
a,*
, Keiko Nakai a, Akira Suwabe a, Koichiro Sera
b
Department of Clinical Pathology, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan Cyclotron Research Center, Iwate Medical University, 348-58 Tomegamori, Takizawa 020-0173, Japan
Abstract A number of considerations suggest that trace element disturbances might occur in patients with renal disease and in hemodialysis (HD) patients. Using particle induced X-ray emission, we demonstrated the relations between serum concentration, urinary excretion of the trace elements and creatinine clearance (Ccr) in randomized 50 patients. To estimate the effects of HD, we also observed the changes of these elements in serum and dialysis fluids during HD. Urinary silicon excretion decreased, and serum silicon concentration increased as Ccr decreased, with significant correlation (r ¼ 0:702, p < 0:001 and r ¼ 0:676, p < 0:0001, respectively). We also observed the increase of serum silicon, and the decrease of silicon in dialysis fluids during HD. These results suggested that reduced renal function and also dialysis contributed to silicon accumulation. Although serum selenium decreased significantly according to Ccr decrease (r ¼ 0:452, p < 0:01), we could detect no change in urinary selenium excretion and no transfer during HD. Serum bromine and urinary excretion of bromine did not correlate to Ccr. However we observed a bromine transfer from the serum to the dialysis fluid that contributed to the serum bromine decrease in HD patients. Ó 2002 Elsevier Science B.V. All rights reserved. PACS: 29.30.Kv; 83.80.Lz Keywords: Particle induced X-ray emission; Human serum; Renal disease; Hemodialysis
1. Introduction It is known that in hemodialysis (HD) patients, serum concentrations of elements may be affected by several factors, i.e. the reduction of excretion in urine, the disturbed absorption by digestive systems and the effects of concentrations in dialysate. Although recent improvement of the dialysis technique made it possible to prevent some serious complications due to these changes of trace ele-
*
Corresponding author. Tel.: +81-19-651-5111; fax: +81-19624-5030. E-mail address: [email protected] (Y. Miura).
ments, problems still remain. Changes in the tissue content of trace elements of patients with renal diseases (RD) who have been treated with or without HD have been only occasionally described. Alfrey and Gary reported that aluminum in brain gray matter was higher in all patients with the dialysis-associated encephalopathy syndrome than any of the control subjects or the other uremic patients on dialysis and suggested that this syndrome might be due to aluminum intoxication [1,2]. Also the analysis of serum from dialyzed patients revealed highly significant elevations in the concentration of silicon. Silicon accumulation is reported to be one of the possible causes of osteopathy and neuropathy in dialysis patients [3,4].
0168-583X/02/$ - see front matter Ó 2002 Elsevier Science B.V. All rights reserved. PII: S 0 1 6 8 - 5 8 3 X ( 0 1 ) 0 1 1 2 2 - 3
444
Y. Miura et al. / Nucl. Instr. and Meth. in Phys. Res. B 189 (2002) 443–449
Serum nickel, zinc and manganese are known to be generally decreased in patients undergoing chronic hemodialysis [5–10]. Using particle induced X-ray emission (PIXE) we have determined concentrations of trace elements in sera of HD patients, RD patients who were not undergoing HD, and normal controls [11–13]. In our data, the HD group had significantly higher silicon concentrations than the normal controls. In general, serum aluminum is known to be elevated in HD patients. Although the RD group had significantly higher aluminum concentrations than in the normal controls, we did not find any significant difference between the HD patients and the normal controls. Both the HD group and the RD group had significantly lower zinc concentrations than the normal controls. Lower bromine concentration in the HD patients, and higher bromine concentration in the RD group were observed, compared to that in normal controls. We demonstrate the relationship between serum concentration, urinary excretion of the trace elements and creatinine clearance (Ccr). Ccr is more commonly used for the clinical assessment of renal function. To estimate the effects of hemodialysis, we also observed the changes of these elements between serum and dialysis fluids during hemodialysis.
2. Experiment 2.1. Subjects Serum and urine samples for trace elements and Ccr analysis were obtained from 50 patients (41 male, 9 female; average age 49.7 years). These patients were admitted to the IWATE Medical University Hospital with various diseases. Five chronic HD patients were examined. There were 5 males (average age: 49.0 years). They received 5-h dialysis 3 times a week by dialyzer with high-performance membrane (polysulfone, polyarylethersulfone, polyacrylonytrile). Dialysate was made by adding one part of a salt solution, Kindary AF2 or AF3 (Fuso, KK, Japan), to 34 parts of reverse osmosis (RO)-treated water. The blood
and dialysis fluids sampling was performed with a sterile syringe before and after the dialysis session (predialysis, postdialysis). 2.2. Measurement of 24 h creatinine clearance In our laboratory the standard procedure for measuring the endogenous 24 h creatinine clearance (24hCcr) is to collect, twenty-four hour urine specimens and blood samples according to standard procedures. The subject’s height and weight were recorded. We measured the creatinine value by use of enzyme-method (creatininase/creatinase/ sarcosine dehydrogenase). The values for the serum concentration, creatinine excretion and endogenous clearance were then calculated. The clearances were calculated in the standard fashion (C ¼ UV/P, C: creatinine clearance, U: urine creatinine, V: urine specimens, P: serum creatinine) and are expressed in ml/min, the amount of creatinine excreted (mg/min) being divided by the serum concentration (mg/ml). 2.3. PIXE analysis A 100 lg of silver was added to 1 ml of sample serum and dialysis fluids (50 lg of silver was added to 1 ml of sample urine), for quantitative analysis as internal standard, by dropping silver nitrate solution. A 10 ll aliquot of the mixture was deposited onto a 4 lm-thick polypropylene backing film and dried at room temperature. These films were used as targets for PIXE [14]. In practice, the thin target films were bombarded with a 2.9 MeV proton beam from the small cyclotron in the Takizawa facility [15]. The X-ray spectra obtained with two Si(Li) X-ray detectors were analyzed by the S A P I X program [16]. A 500 lm polystyrene film was inserted in front of one of the two detectors to absorb low-energy X-rays and thereby improve detection of the medium- and heavy-Z elements ( P Ca). No film was used in front of the other detector that was used to detect low-Z elements (
Y. Miura et al. / Nucl. Instr. and Meth. in Phys. Res. B 189 (2002) 443–449
445
Fig. 1. The procedure of PIXE spectrum analysis. (A) PIXE spectrum from serum, (B) Determination of a basic background function, (C-1, C-2) Peak fitting with S A P I X program.
3. Results 3.1. Relationship between urinary excretion or serum concentration and 24hCcr in each element Table 1 shows the correlation between urinary excretion or serum concentration and 24hCcr. Urinary silicon excretion decreased, and serum silicon concentration increased as 24hCcr decreased, with a significant correlation (r ¼ 0:702, p < 0:001, y ¼ 1:667x þ 93:200, n ¼ 50 and r ¼ Table 1 Relationship between urinary excretion or serum concentration and creatinine clearance (24hCcr) Urine
Serum
Element
r
p
r
p
Mg Al Si P Ca Fe Cu Zn Se Br Rb Sr
0.383 0.039 0.702 0.405 0.630 0.196 0.152 0.103 0.202 0.216 0.346 0.470
<0.01 NS <0.0001 <0.01 <0.001 NS NS NS NS NS NS <0.01
0.331 0.125 0.676 0.309 0.138 0.139 0.227 0.190 0.452 0.126 0.677 0.069
NS NS <0.0001 NS NS NS NS NS <0.01 NS NS NS
r ¼ Correlation coefficient, p ¼ probability value, n ¼ 50.
0:676, p < 0:0001, y ¼ 136:992 logðxÞ þ 313:803, n ¼ 42, respectively) (Fig. 2(A-1) and (A-2)). Although serum selenium decreased significantly according to 24hCcr decrease (r ¼ 0:452, p < 0:01, y ¼ 0:005x þ 0:811, n ¼ 49) (Fig. 2(C)), we could detect no change in urinary selenium excretion. Urinary magnesium excretion decreased significantly according to 24hCcr decrease (r ¼ 0:383, p < 0:01, y ¼ 6:835x þ 963:629, n ¼ 50) (Fig. 2(D)), but we could detect no change in serum magnesium concentration. 3.2. The changes of trace elements levels in serum and dialysis fluids before and after hemodialysis Table 2 shows the change of trace elements levels in serum and dialysis fluid before and after HD. Paired comparisons in serum and dialysis fluid indicated a statistical significant difference for p < 0:05 for the silicon and bromine. After HD, the levels of silicon in serum significantly increased, and the levels of silicon in dialysis fluid significantly decreased (Fig. 3). After HD, the levels of bromine in serum significantly decreased, and the levels of bromine in dialysis fluid significantly increased (Fig. 4). After HD, the levels of zinc in serum significantly increased (data not shown). There were not significant change during HD treatment in magnesium, aluminum and
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Fig. 2. Relationship between urinary Si, Mg excretion or serum Si, Se concentration and 24hCcr.
Table 2 Changes of element concentration in serum and dialysis fluid before and after hemodialysis (n ¼ 5) After/before ratio (mean SD) Element
Serum
Dialysis fluid
Mg Al Si Zn Se Br
1:10 1:23 0:79 0:20 3:05 1:64a 1:54 0:39a 1:00 0:60 0:58 0:16a
1:10 1:25 1:12 0:62 0:25 0:12a 0:85 0:10 1:00 0:50 1:24 0:26a
a
Difference significant for p < 0:05 in a t-test.
selenium. Total serum protein values increased from 6:5 0:2 g/dl before HD to 7:5 0:6 g/dl after HD.
4. Discussion and conclusion In HD patients, accumulation of aluminum has been reported. Aluminum encephalopathy and aluminum-related bone disease are important trace element-related complications [18,19]. Dialysis itself might be an important cause of aluminum
accumulation [20,21]. Platts et al. [20] reported that patients with dialysis dementia in England were detected in high percentages when using tap water containing a high concentration of aluminum for HD. In this context, using reverse osmosed water for preparing the dialysate may prevent accumulation of aluminum. Accumulation of aluminum via the oral intake of aluminum containing phosphate binders is well known. But in this context, using another phosphate binder may prevent accumulation of aluminum. Also we did not find any significant difference between serum aluminum concentrations in HD patients and normal controls [13]. There was not significant change during HD treatment in aluminum. Serum aluminum and urinary excretion of aluminum did not correlate to 24hCcr. Serum Si levels of chronic HD patients are reported to be high [3,4]. Thus high silicon concentration in the chronic HD patients may probably be due to impaired excretion of silicon through the urine. We previously reported that serum silicon concentrations in HD patients were significantly higher than in normal subjects [13]. Urinary silicon excretion decreased, and serum silicon concentra-
Y. Miura et al. / Nucl. Instr. and Meth. in Phys. Res. B 189 (2002) 443–449
447
Fig. 3. Change of Si levels in serum and dialysis fluid before and after hemodialysis.
tion increased as 24hCcr decreased, with significant correlation. This result suggests that the accumulation of serum silicon concentration in the HD was apparently caused by reduction of renal function. Another possible cause for accumulation of serum silicon in the HD patients is HD treatment using water loaded with silicon [13,22]. We observed an increase of serum silicon, and decreased silicon in the dialysis fluids during HD. Silicon is found in brain, liver, lung, kidney, bone, blood, urine and sweat of humans. Abnormal accumulation of silicon causes hepatic disease [23,24], neuropathy [4] and bone disease [25]. In general, serum magnesium concentrations have been reported to elevate in HD patients because of decrease of the magnesium excretion in a kidney [26]. Previously, we reported that the HD and RD patients did not show any significant elevation of serum magnesium compared to normal
Fig. 4. Change of Br levels in serum and dialysis fluid before and after hemodialysis.
subjects [13]. In the present study, urinary magnesium excretion decreased as 24hCcr decreased with significant correlation. Selenium is one of the elements whose clinical importance for patients on HD has not been clearly evaluated [27]. In the present study, although serum selenium decreased significantly according to 24hCcr decrease, we could detect no change in urinary selenium excretion. These results suggest that the change of serum selenium concentrations in HD patients is not influenced by renal function. We did not find any significant difference between serum selenium and the selenium in the dialysis fluids during HD treatment. The low selenium level may be one of the factors responsible for the increased incidence of malignancy in patients with chronic renal failure (CRF).
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This is supported by several facts such as: (a) low serum selenium levels detected in patients with malignant diseases, (b) the higher cancer incidence in inhabitants of low-selenium areas [28], and (c) the ability of selenium to inhibit many types of experimental carcinogenesis. Previously, we reported that both the HD patients and the RD patients had significantly lower serum zinc concentrations than the normal subjects [13]. In the present study, urinary zinc excretion and serum zinc concentrations did not correlate to 24hCcr. These results suggest that the lowering of serum zinc concentrations in HD and RD patients is not influenced by renal function. Clinical characteristics of chronic zinc decrease are poor growth, poor wound healing, taste disturbance, poor appetite and hypogonadism. In chronic HD patients, similar clinical symptoms are often observed. It is known that zinc plays an important role in the nutritional condition of chronic HD patients [29]. The low zinc concentrations in chronic HD patients may probably be due to the restricted food intake combined with impaired absorption of zinc through the intestine. In the present study, although we observed a significant increase of serum zinc concentrations in HD patients during HD treatment, we could not observed a significant change of zinc in the dialysis fluids during HD. So supplementation of zinc should be kept in mind in the treatment of CRF. Previously, we reported that lower bromine concentration in the HD patients, and higher bromine concentration in the RD patients were observed, compared to that in normal subjects [13]. In the present study, serum bromine and urinary excretion of bromine did not correlate to 24hCcr. These results suggest that the change of serum bromine concentrations in HD and RD patients is not influenced by renal function. We demonstrated bromine transfer from serum to dialysis fluid that contributed to the serum bromine decrease in HD patients. In conclusion, in confirmation of previous studies, we have demonstrated an increase of the concentration in serum silicon of the patients with HD patients [13]. The effects of renal function and HD treatment are to cause an increase in serum silicon concentration. To prevent some complica-
tions in HD patients, it is important to regulate levels of trace elements.
Acknowledgements We are indebted to the staff of Nishina Memorial Cyclotron Center (NMCC). We would like to thank Michiro Sato for the help with the sample preparation. We would like to express our sincere gratitude to Prof. Chuichi Itoh for his helpful discussion on this paper.
References [1] A.C. Alfrey, J.M. Michell, J. Burks, S.R. Contigulia, J.H. Holmes, Trans. Am. Soc. Art. Intern. Org. 18 (1972) 257. [2] A.C. Alfrey, G.R. LeGendr, W.D. Kaehney, New Engl. J. Med. 294 (1976) 184. [3] S. Hosokawa, A. Oyamaguchi, O. Yoshida, Nephron 55 (1990) 375. [4] C.O. Hershey, E.S. Ricnati, L.A. Hershey, A.W. Varnes, P.J.M. Lavin, M. Strain, Neurology 33 (1983) 786. [5] S. Hosokawa, Int. J. Artif. Organs. 8 (1985) 245. [6] G.C. Cotziiacs, Physiol Rhysiol Rev. 38 (1958) 503. [7] S. Hosokawa, Int. J. Artif. Organs. 10 (1987) 14. [8] S. Hosokawa, H. Nishitani, K. Umemura, T. Tomoyoshi, K. Sawanishi, O. Yoshida, Nephron. 45 (1987) 151. [9] K.S. Mahajan, S.A. Prasad, P. Rabbani, W.A. Priggs, D.F. McDonald, J. Lab. Clin. Med. 94 (1979) 693. [10] J.A. Halsted, J.C. Smith, Lancet (1970) 322. [11] Y. Miura, K. Nakai, C. Itoh, M. Sato, K. Sera, NMCC Annu. Rep. 3 (1995) 65. [12] Y. Miura, K. Nakai, C. Itoh, M. Sato, K. Sera, NMCC Annu. Rep. 5 (1997) 180. [13] Y. Miura, K. Nakai, K. Sera, M. Sato, Nucl. Instr. and Meth. B 150 (1999) 218. [14] S. Futatsugawa, S. Hatakeyama, Y. Saitou, K. Sera, NMCC Ann. Rep. 1 (1993) 70. [15] K. Sera, T. Yanagisawa, et al., Int. J. PIXE 2 (3) (1992) 325. [16] K. Sera, T. Yanagisawa, H. Tsunoda, S. Futatsugawa, S. Hatakeyama, Y. Saitou, S. Suzuki, H. Orihara, Int. J. PIXE 3 (4) (1993) 319. [17] K. Sera, S. Futatsugawa, NMCC Annu. Rep. 1 (1993) 55. [18] J.A. O’Hare, D.J. Murnaghan, New. Engl. J. Med. 306 (1982) 654. [19] G.S. Warker, A.M. Peacock, D.J.A. Robinson, et al., Kidney Int. 21 (1982) 411. [20] M.M. Platts, G.C. Goode, J.S. Hislop, Brit. Med. J. ii (1977) 657.
Y. Miura et al. / Nucl. Instr. and Meth. in Phys. Res. B 189 (2002) 443–449 [21] W.D. Kaehny, A.C. Alfrey, R.E. Holfman, W.J. Shorr, Kidney Int. 12 (1977) 361. [22] P.C. D’Haese, F.A. Shoheen, S.O. Huraib, et al., Nephrol. Dial. Transplant. 10 (1995) 1838. [23] A.S.Y. Leong, Annales Acad. Med. 12 (1983) 304. [24] T. Laohapand, E.M. Osman, A.R. Morley, Proc. EDTA 19 (1982) 143. [25] K. Schwarz, D.B. Milne, Nature 239 (1972) 333.
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[26] W.E.C. Wacker, B.L. Vallee, New Engl. J. Med. 259 (1958) 431. [27] G. Kallistratos, A. Evanigelou, K. Sefriadis, P. Veezyraki, K. Barbouti, Nephron 41 (1985) 217. [28] Keshan Disease Research Group of the Chinese Academy of Medical Science, Chinese. Med. J. 92 (1979) 471. [29] C.J. Condon, R.M. Freeman, Annals Intern. Med. 73 (1970) 531.
Trace elements in renal disease and hemodialysis Yoshinori Miura a b
a,*
, Keiko Nakai a, Akira Suwabe a, Koichiro Sera
b
Department of Clinical Pathology, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan Cyclotron Research Center, Iwate Medical University, 348-58 Tomegamori, Takizawa 020-0173, Japan
Abstract A number of considerations suggest that trace element disturbances might occur in patients with renal disease and in hemodialysis (HD) patients. Using particle induced X-ray emission, we demonstrated the relations between serum concentration, urinary excretion of the trace elements and creatinine clearance (Ccr) in randomized 50 patients. To estimate the effects of HD, we also observed the changes of these elements in serum and dialysis fluids during HD. Urinary silicon excretion decreased, and serum silicon concentration increased as Ccr decreased, with significant correlation (r ¼ 0:702, p < 0:001 and r ¼ 0:676, p < 0:0001, respectively). We also observed the increase of serum silicon, and the decrease of silicon in dialysis fluids during HD. These results suggested that reduced renal function and also dialysis contributed to silicon accumulation. Although serum selenium decreased significantly according to Ccr decrease (r ¼ 0:452, p < 0:01), we could detect no change in urinary selenium excretion and no transfer during HD. Serum bromine and urinary excretion of bromine did not correlate to Ccr. However we observed a bromine transfer from the serum to the dialysis fluid that contributed to the serum bromine decrease in HD patients. Ó 2002 Elsevier Science B.V. All rights reserved. PACS: 29.30.Kv; 83.80.Lz Keywords: Particle induced X-ray emission; Human serum; Renal disease; Hemodialysis
1. Introduction It is known that in hemodialysis (HD) patients, serum concentrations of elements may be affected by several factors, i.e. the reduction of excretion in urine, the disturbed absorption by digestive systems and the effects of concentrations in dialysate. Although recent improvement of the dialysis technique made it possible to prevent some serious complications due to these changes of trace ele-
*
Corresponding author. Tel.: +81-19-651-5111; fax: +81-19624-5030. E-mail address: [email protected] (Y. Miura).
ments, problems still remain. Changes in the tissue content of trace elements of patients with renal diseases (RD) who have been treated with or without HD have been only occasionally described. Alfrey and Gary reported that aluminum in brain gray matter was higher in all patients with the dialysis-associated encephalopathy syndrome than any of the control subjects or the other uremic patients on dialysis and suggested that this syndrome might be due to aluminum intoxication [1,2]. Also the analysis of serum from dialyzed patients revealed highly significant elevations in the concentration of silicon. Silicon accumulation is reported to be one of the possible causes of osteopathy and neuropathy in dialysis patients [3,4].
0168-583X/02/$ - see front matter Ó 2002 Elsevier Science B.V. All rights reserved. PII: S 0 1 6 8 - 5 8 3 X ( 0 1 ) 0 1 1 2 2 - 3
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Y. Miura et al. / Nucl. Instr. and Meth. in Phys. Res. B 189 (2002) 443–449
Serum nickel, zinc and manganese are known to be generally decreased in patients undergoing chronic hemodialysis [5–10]. Using particle induced X-ray emission (PIXE) we have determined concentrations of trace elements in sera of HD patients, RD patients who were not undergoing HD, and normal controls [11–13]. In our data, the HD group had significantly higher silicon concentrations than the normal controls. In general, serum aluminum is known to be elevated in HD patients. Although the RD group had significantly higher aluminum concentrations than in the normal controls, we did not find any significant difference between the HD patients and the normal controls. Both the HD group and the RD group had significantly lower zinc concentrations than the normal controls. Lower bromine concentration in the HD patients, and higher bromine concentration in the RD group were observed, compared to that in normal controls. We demonstrate the relationship between serum concentration, urinary excretion of the trace elements and creatinine clearance (Ccr). Ccr is more commonly used for the clinical assessment of renal function. To estimate the effects of hemodialysis, we also observed the changes of these elements between serum and dialysis fluids during hemodialysis.
2. Experiment 2.1. Subjects Serum and urine samples for trace elements and Ccr analysis were obtained from 50 patients (41 male, 9 female; average age 49.7 years). These patients were admitted to the IWATE Medical University Hospital with various diseases. Five chronic HD patients were examined. There were 5 males (average age: 49.0 years). They received 5-h dialysis 3 times a week by dialyzer with high-performance membrane (polysulfone, polyarylethersulfone, polyacrylonytrile). Dialysate was made by adding one part of a salt solution, Kindary AF2 or AF3 (Fuso, KK, Japan), to 34 parts of reverse osmosis (RO)-treated water. The blood
and dialysis fluids sampling was performed with a sterile syringe before and after the dialysis session (predialysis, postdialysis). 2.2. Measurement of 24 h creatinine clearance In our laboratory the standard procedure for measuring the endogenous 24 h creatinine clearance (24hCcr) is to collect, twenty-four hour urine specimens and blood samples according to standard procedures. The subject’s height and weight were recorded. We measured the creatinine value by use of enzyme-method (creatininase/creatinase/ sarcosine dehydrogenase). The values for the serum concentration, creatinine excretion and endogenous clearance were then calculated. The clearances were calculated in the standard fashion (C ¼ UV/P, C: creatinine clearance, U: urine creatinine, V: urine specimens, P: serum creatinine) and are expressed in ml/min, the amount of creatinine excreted (mg/min) being divided by the serum concentration (mg/ml). 2.3. PIXE analysis A 100 lg of silver was added to 1 ml of sample serum and dialysis fluids (50 lg of silver was added to 1 ml of sample urine), for quantitative analysis as internal standard, by dropping silver nitrate solution. A 10 ll aliquot of the mixture was deposited onto a 4 lm-thick polypropylene backing film and dried at room temperature. These films were used as targets for PIXE [14]. In practice, the thin target films were bombarded with a 2.9 MeV proton beam from the small cyclotron in the Takizawa facility [15]. The X-ray spectra obtained with two Si(Li) X-ray detectors were analyzed by the S A P I X program [16]. A 500 lm polystyrene film was inserted in front of one of the two detectors to absorb low-energy X-rays and thereby improve detection of the medium- and heavy-Z elements ( P Ca). No film was used in front of the other detector that was used to detect low-Z elements (
Y. Miura et al. / Nucl. Instr. and Meth. in Phys. Res. B 189 (2002) 443–449
445
Fig. 1. The procedure of PIXE spectrum analysis. (A) PIXE spectrum from serum, (B) Determination of a basic background function, (C-1, C-2) Peak fitting with S A P I X program.
3. Results 3.1. Relationship between urinary excretion or serum concentration and 24hCcr in each element Table 1 shows the correlation between urinary excretion or serum concentration and 24hCcr. Urinary silicon excretion decreased, and serum silicon concentration increased as 24hCcr decreased, with a significant correlation (r ¼ 0:702, p < 0:001, y ¼ 1:667x þ 93:200, n ¼ 50 and r ¼ Table 1 Relationship between urinary excretion or serum concentration and creatinine clearance (24hCcr) Urine
Serum
Element
r
p
r
p
Mg Al Si P Ca Fe Cu Zn Se Br Rb Sr
0.383 0.039 0.702 0.405 0.630 0.196 0.152 0.103 0.202 0.216 0.346 0.470
<0.01 NS <0.0001 <0.01 <0.001 NS NS NS NS NS NS <0.01
0.331 0.125 0.676 0.309 0.138 0.139 0.227 0.190 0.452 0.126 0.677 0.069
NS NS <0.0001 NS NS NS NS NS <0.01 NS NS NS
r ¼ Correlation coefficient, p ¼ probability value, n ¼ 50.
0:676, p < 0:0001, y ¼ 136:992 logðxÞ þ 313:803, n ¼ 42, respectively) (Fig. 2(A-1) and (A-2)). Although serum selenium decreased significantly according to 24hCcr decrease (r ¼ 0:452, p < 0:01, y ¼ 0:005x þ 0:811, n ¼ 49) (Fig. 2(C)), we could detect no change in urinary selenium excretion. Urinary magnesium excretion decreased significantly according to 24hCcr decrease (r ¼ 0:383, p < 0:01, y ¼ 6:835x þ 963:629, n ¼ 50) (Fig. 2(D)), but we could detect no change in serum magnesium concentration. 3.2. The changes of trace elements levels in serum and dialysis fluids before and after hemodialysis Table 2 shows the change of trace elements levels in serum and dialysis fluid before and after HD. Paired comparisons in serum and dialysis fluid indicated a statistical significant difference for p < 0:05 for the silicon and bromine. After HD, the levels of silicon in serum significantly increased, and the levels of silicon in dialysis fluid significantly decreased (Fig. 3). After HD, the levels of bromine in serum significantly decreased, and the levels of bromine in dialysis fluid significantly increased (Fig. 4). After HD, the levels of zinc in serum significantly increased (data not shown). There were not significant change during HD treatment in magnesium, aluminum and
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Fig. 2. Relationship between urinary Si, Mg excretion or serum Si, Se concentration and 24hCcr.
Table 2 Changes of element concentration in serum and dialysis fluid before and after hemodialysis (n ¼ 5) After/before ratio (mean SD) Element
Serum
Dialysis fluid
Mg Al Si Zn Se Br
1:10 1:23 0:79 0:20 3:05 1:64a 1:54 0:39a 1:00 0:60 0:58 0:16a
1:10 1:25 1:12 0:62 0:25 0:12a 0:85 0:10 1:00 0:50 1:24 0:26a
a
Difference significant for p < 0:05 in a t-test.
selenium. Total serum protein values increased from 6:5 0:2 g/dl before HD to 7:5 0:6 g/dl after HD.
4. Discussion and conclusion In HD patients, accumulation of aluminum has been reported. Aluminum encephalopathy and aluminum-related bone disease are important trace element-related complications [18,19]. Dialysis itself might be an important cause of aluminum
accumulation [20,21]. Platts et al. [20] reported that patients with dialysis dementia in England were detected in high percentages when using tap water containing a high concentration of aluminum for HD. In this context, using reverse osmosed water for preparing the dialysate may prevent accumulation of aluminum. Accumulation of aluminum via the oral intake of aluminum containing phosphate binders is well known. But in this context, using another phosphate binder may prevent accumulation of aluminum. Also we did not find any significant difference between serum aluminum concentrations in HD patients and normal controls [13]. There was not significant change during HD treatment in aluminum. Serum aluminum and urinary excretion of aluminum did not correlate to 24hCcr. Serum Si levels of chronic HD patients are reported to be high [3,4]. Thus high silicon concentration in the chronic HD patients may probably be due to impaired excretion of silicon through the urine. We previously reported that serum silicon concentrations in HD patients were significantly higher than in normal subjects [13]. Urinary silicon excretion decreased, and serum silicon concentra-
Y. Miura et al. / Nucl. Instr. and Meth. in Phys. Res. B 189 (2002) 443–449
447
Fig. 3. Change of Si levels in serum and dialysis fluid before and after hemodialysis.
tion increased as 24hCcr decreased, with significant correlation. This result suggests that the accumulation of serum silicon concentration in the HD was apparently caused by reduction of renal function. Another possible cause for accumulation of serum silicon in the HD patients is HD treatment using water loaded with silicon [13,22]. We observed an increase of serum silicon, and decreased silicon in the dialysis fluids during HD. Silicon is found in brain, liver, lung, kidney, bone, blood, urine and sweat of humans. Abnormal accumulation of silicon causes hepatic disease [23,24], neuropathy [4] and bone disease [25]. In general, serum magnesium concentrations have been reported to elevate in HD patients because of decrease of the magnesium excretion in a kidney [26]. Previously, we reported that the HD and RD patients did not show any significant elevation of serum magnesium compared to normal
Fig. 4. Change of Br levels in serum and dialysis fluid before and after hemodialysis.
subjects [13]. In the present study, urinary magnesium excretion decreased as 24hCcr decreased with significant correlation. Selenium is one of the elements whose clinical importance for patients on HD has not been clearly evaluated [27]. In the present study, although serum selenium decreased significantly according to 24hCcr decrease, we could detect no change in urinary selenium excretion. These results suggest that the change of serum selenium concentrations in HD patients is not influenced by renal function. We did not find any significant difference between serum selenium and the selenium in the dialysis fluids during HD treatment. The low selenium level may be one of the factors responsible for the increased incidence of malignancy in patients with chronic renal failure (CRF).
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This is supported by several facts such as: (a) low serum selenium levels detected in patients with malignant diseases, (b) the higher cancer incidence in inhabitants of low-selenium areas [28], and (c) the ability of selenium to inhibit many types of experimental carcinogenesis. Previously, we reported that both the HD patients and the RD patients had significantly lower serum zinc concentrations than the normal subjects [13]. In the present study, urinary zinc excretion and serum zinc concentrations did not correlate to 24hCcr. These results suggest that the lowering of serum zinc concentrations in HD and RD patients is not influenced by renal function. Clinical characteristics of chronic zinc decrease are poor growth, poor wound healing, taste disturbance, poor appetite and hypogonadism. In chronic HD patients, similar clinical symptoms are often observed. It is known that zinc plays an important role in the nutritional condition of chronic HD patients [29]. The low zinc concentrations in chronic HD patients may probably be due to the restricted food intake combined with impaired absorption of zinc through the intestine. In the present study, although we observed a significant increase of serum zinc concentrations in HD patients during HD treatment, we could not observed a significant change of zinc in the dialysis fluids during HD. So supplementation of zinc should be kept in mind in the treatment of CRF. Previously, we reported that lower bromine concentration in the HD patients, and higher bromine concentration in the RD patients were observed, compared to that in normal subjects [13]. In the present study, serum bromine and urinary excretion of bromine did not correlate to 24hCcr. These results suggest that the change of serum bromine concentrations in HD and RD patients is not influenced by renal function. We demonstrated bromine transfer from serum to dialysis fluid that contributed to the serum bromine decrease in HD patients. In conclusion, in confirmation of previous studies, we have demonstrated an increase of the concentration in serum silicon of the patients with HD patients [13]. The effects of renal function and HD treatment are to cause an increase in serum silicon concentration. To prevent some complica-
tions in HD patients, it is important to regulate levels of trace elements.
Acknowledgements We are indebted to the staff of Nishina Memorial Cyclotron Center (NMCC). We would like to thank Michiro Sato for the help with the sample preparation. We would like to express our sincere gratitude to Prof. Chuichi Itoh for his helpful discussion on this paper.
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