Lead, Cadmium, Selenium, Strontium, And Aluminum Levels In Renal Failure Patients In China

Background and objective:Trace elements is chemical elements and it's content is less than 0.01%in the human body.Essential trace elements include iron,zinc,copper,selenium and so on.In addition,there are some toxic trace elements which enter the body through a variety of ways from the outside environment,such as mercury,cadmium,lead.Although content of trace elements in the body is small,the roles of trace elements are very important.Trace elements involves in a variety of enzymes and metabolism of active substances in the human body in order to maintain the body balance.In the early seventies,abnormal distribution of trace elements had been found to play a role in the pathogenesis of uremia,which may be not only the result of uremia,but also causes of some complications of uremia.So far,data in many literatures have pointed to abnormal distribution of trace elements can cause renal damage in normal healthy people,but literature data on abnormal distribution of trace elements in renal failure patients either or not treated by dialysis are scarce, especially in Chinese renal failure patients. Lead(Pb) and cadmium(Cd) are widespread industrial poisons,which extensively exist and can cause many damages in the human body.Accumulation in renal failure patients is very common and is associated with many complications in renal failure patients such as inflammation and anemia.Selenium(Se) is an essential trace elements,with a variety of important physiological functions.The most important function is that it is the composition of glutathione peroxidase enzyme,which plays an important role in antioxidant in the human bady.Selenium deficiency is associated with many complications in renal failure patients such as heart disease.Strontium(Sr) and Aluminum(Al) also extensively exists in human bodies,accumulation of this element is closely associated with renal osteodystrophy in renal failure patients.The aim of this study consistes in the evaluation of the concentration of trace metals(Lead,Cadmium,Selenium,Strontium and Aluminum so on) in Chinese patients presenting different degrees of chronic renal insufficiency patients as well as in post-transplant patients and hemodialysis patients and investigates a possible relationship with clinical and personal factors.Methods:1.Patients and specimens1.1 Subjects with normal renal functionWhole blood and serum samples were collected from 62 volunteers with normal renal function(NRF),which were mainly students in the Medical College of Shandong University.1.2 Patients with chronic renal insufficiencyChronic renal insufficiency(CRI) patients(N=81) were recruited from 5 hospitals in different regions of Shandong and Jiangsu Provinces.Based on the creatinine clearance(Ccr),patients were divided in two groups:Ccr≥50 ml/min(N=25) and Ccr＜50 ml/min(N=56).The overall mean of Ccr was 56.3±14.7 and 25.2±13.3 ml/min in two groups,respectively.1.3 Patients in dialysis 293 hemodialysis(HD) patients were recruited from 6 different centers in China between June 2007 and October 2008.Three centers were located in the Shandong Province,Jinan,Linyi and Yantai center respectively.One center in the Beijing area.One center in Liaoning Province and One center in Jiangsu Province.The whole blood and serum samples were taken before the start of the HD session. Three samples of tap water and reverse osmosis(RO) water were collected from each dialysis center at different days,as well as five samples of the dialysis fluid. Moreover,serum samples of 172 dialysis patients from Belgium(N=67,2 centers), Portugal(N=34,1 center) and Paraguay(N=71,2 centers) were also collected.1.4 Post-transplant patientsTrace metals under study were also determined in 60 renal post-transplantation patients from Shandong Province.All patients underwent a successful transplantation at least 2 months before being included in the present study and did not have had an acute organ rejection.Patients were divided in 2 groups:Ccr＞ 50 ml/min(N= 42) and Ccr＜50 ml/min(N=18).The overall mean of Ccr was 83.5±23.3 and 33.8±15.4 ml/min in two groups respectively.1.5 Investigation of Patients' informationA questionnaire with personal,clinical and dietary data,together with information about the dialysis modalities of each center was completed for each Chinese patient and each participating center respectively.2.Analyses2.1 Lead and Cadmium in whole blood and water,Selenium and Aluminum(Al) in serum were analyzed using a SIMAA 6000 atomic absorption spectrometer.2.1.1 Pb and Cd in whole blood were measured after a 1:5 dilution in a 0.4% NH₄H₂PO₄-0.4%oxalic acid-2.0%Triton X-100 and 0.2%HNO₃ solution2.1.2 For the measurement of Se 50μL of serum was diluted in 120μL of a 0.1% Triton X-100-0.2%HNO₃ solution to which 75μL Pd/Mg matrix modifier was added.2.1.3 Al in serum was measured after a 1:3 dilution of the samples in RO water. 2.2 Sr in serum and water was analyzed using a Zeeman 3030 atomic absorption spectrometer.Sr in serum samples was determined after a fourfold dilution in a 0.5 ml/L Triton X-100-1 ml/L HNO₃ solution.2.3 Total serum Calcium(Ca) concentration was measured with flame atomic absorption spectrometry after a 1:50 dilution of the samples in 0.1%La (NO₃)₃·6H₂O.2.4 Automatic blood analyzer was used to measure Hematocrit(Hct),automatic biochemical analyzer was used to measure serum albumin level and serum creatinine.2.5 As both Pb and Cd are almost exclusively stored in red blood cells and CRF patients either or not treated by dialysis all have a certain degree of anemia,the concentration of whole blood Pb and Cd in these subjects are also reported after correction for Hct to allow accurate comparison with subjects with NRF.Hereto the following formula:[Corrected concentration]= H/Hct^*[Measured concentration]was used,where H = the mean Hct of the NRF population under study and was defined as 0.4.Results:1.Distribution and Comparison of various trace elements in different groups.1.1 Lead and Cadmium.1.1.1 The mean blood Pb and Cd level was 90.2±38.2 and 1.61±2.20μg/L in subjects with NRF(N= 42) respectively.Significant differences were found between non-smokers(N=33,0.81±0.24μg/L) and smokers(N=9,3.17±3.18μg/L)(P＜0.01).1.1.2 CRI patients with a Ccr≥50 ml/min(N=25) showed a mean blood Pb and Cd evel of 73.3±48.5 and 1.48±0.99μg/L respectively,and in patients with a Ccr＜50 ml/min(N=56) the mean blood Pb and Cd levels was 46.4±28.0 and 1.46±1.02μg/L respectively.No difference was found between two groups(Ccr≥and ＜50 ml/min).Compared to the subjects with NRF however,the overall mean Cd concentration was higher in CRI patients(P＜0.05).1.1.3 The overall mean blood Pb and Cd concentration in the HD population(N= 135) was 87.7 4±32.4 and 1.87±1.05μg/L respectively,0.7%HD patient hac a Pb level above the generally accepted cut-off level of 200μg/L and 20.7%showed a Cd level above the normal upper limit of 2.5μg/L.The blood Cd level in HD patients was also significantly higher compared to that of subjects with CRI(P＜0.01).1.1.4 Post-transplant patients with a Ccr≥50 ml/min(N=42) showed a mean blood Pb and Cd of 97.4±32.1μg/L and 1.70±0.77μg/L respectively,in patients with a Ccr＜50 ml/min(N=18) was 85.4 + 38.7 and 2.50±2.01μg/L respectively. Compared to the subjects with NRF,the overall Cd levels were higher in the post-transplant patients(P＜0.01).1.1.5 Significantly decreased Hct levels were found in CRI patients with a Ccr＜50 ml/min(27.7±6.5%) and HI) patients(30.4±8.3%) as compared to subjects with NRF(39.6±8.7%).Within the total group of renal failure patients(CRI,HD and post-transplant) significant positive correlations between Hct and Pb(r=0.276, P＜0.01),between Hct and blood Cd(r=0.307,P＜0.01) were found,After correcting the result of Pb and Cd for Hct,a mean blood Pb level in dialysis patients of 112.7±42.9μg/L was found,which was significantly higher compared to that of subjects with NRF(P＜0.01) as well as vs the corrected levels of the CRI patients(P＜0.01).Significant(P＜0.05) differences in blood Cd levels were found between the Ccr≥50 ml/min and Ccr＜50 ml/min groups of CRI and post-transplant patients.1.2 Selenium.1.2.1 The mean serum Se level was 65.9±8.1μg/L in subjects with NRF(N=42).1.2.2 CRI patients with a Ccr≥50 ml/min(N=25) showed a mean serum Se level of 54.6±12.6μg/L(P＜0.01 vs NRF),while in patients with a Ccr＜50 ml/min (N=56) the mean serum Se level was 38.4±15.9μg/L(P＜0.01 vs NRF and P＜0.01 vs Ccr≥50 ml/min)1.2.3 45.9%HD patients showed a Se level below the normal cut-off level(45μg/L),whilst the overall mean Se concentration of the HD population(N=135) was 46.8±12.6μg/L,a value which was significantly lower(P＜0.01) compared to subjects with NRF.1.2.4 In the group of post-transplant patients with a Ccr≥50 ml/min(N=42) the mean serum Se level was 66.6±15.7μg/L,as compared to 52.9±15.4μg/L(P＜0.01) in post-transplant patients with a Ccr＜50 ml/min(N=18).Compared with HD patients,the serum Se level of post-transplant patients with a Ccr≥50 ml/min was significantly higher(P＜0.01).1.3 Strontium and Aluminum.1.3.1 The mean serum Sr level in subjects with NRF(N=62) was 32.4±10.5μg/L, and the mean serum Al level in subjects with NRF was bellow 2μg/L.1.3.2 CRI patients with a Ccr≥50 ml/min(N=25) showed a mean Sr level of 46.6±14.3,whilst those with a Ccr＜50 ml/min(N=56) had a concentration of 57.7±23.9(P＜0.01).1.3.3 The overall mean serum Sr and Al levels of dialysis patients(N=293) were 72.1±17.1 and 23.7±21.5μg/L(P＜0.01 vs CRI patients) respectively.7.8% HD patient had a Sr level above the generally accepted cut-off level of 100μg/L and 29,7%showed a Al level above the normal upper limit of 30μg/L.The mean serum Sr level in Chinese dialysis patients was significantly higher than that noted in Belgian(34.0±7.9μg/L) and Portugese(41.5±9.2μg/L) dialysis patients.1.3.4 Post-transplant patients with a Ccr≥50 ml/min(N=42) showed a mean Sr of 49.6±15.5,in patients with a Ccr＜50 ml/min(N=18) was 61.3±18.1(P＜0.01).2.Relationship with clinical and personal factors in dialysis patients.2.1 In the dialysis patients,compared to HD patients that were treated for＜2 years,the serum Se level in HD patients treated＞6 years was significantly lower (P＜0.05),whilst the blood Pb and Cd levels(both non-Hct-corrected and Hct-corrected) in the latter population were significantly higher(P＜0.01).In line herewith,a negative correlation between Se and time on dialysis(r=-0.225,P＜0.01),and positive correlations between non Hct-corrected Pb(r=0.363,P＜0.01), Cd(r=0.298,P＜0.01) and time on dialysis were noted,which became even more pronounced when Hct correction was made(Pb,r=0.495,P＜0.01;Cd,r=0.312,P＜0.01).2.2 The overall mean serum albumin level in HD patients was 35.2±4.4g/L (N=76),a value which was significantly lower(P＜0.01) compared to subjects with NRF(44.1±2.8 g/L).A positive correlation between serum Se and albumin levels(r=0.293,P＜0.05) was noted in HD patients.3.Comparison of trace elements in blood in the Chinese dialysis centers under study.3.1 Comparison of the non-Hct-corrected mean blood Pb and Cd levels in different centers showed more pronounced differences,ranging from 65.6±18.7μg/L,in theYantai center with the lowest value up to 98.2±30.1μg/L in the Beijing center with the highest level for Pb(P＜0.01) and 1.49±1.01μg/L in the Linyi center up to 2.24±1.12μg/L in the Beijing center for Cd respectively.3.2 A center-to-center comparison of the mean serum Se level of the HD population showed relatively minor however,significant differences,ranging from a mean value of 42.6±10.3μg/L in the Jiangsu center with the lowest value up to 51.4±11.9μg/L(P＜0.05) in the Jinan center with the highest level.3.3 A center-to-center comparison of the mean serum Sr levels of the dialysis patients indicated minor,ranging from 62.5±11.6μg/L in theYantai center with the lowest value up to 77.5±16.9μg/L in the Beijing center with the highest level for Sr(P＜0.05).4.Trace elements in dialysate in the dialysis centersWe found that the concentrations of Pb and Cd in the dialysate were significantly higher than that of the RO water in most centers.Significant positive correlations between the mean blood and dialysate Pb levels(r=0.702,P＜0.05) and between the mean blood and dialysate Cd levels(r=0.618,P＜0.05) were noted.The Sr level of the dialysate was a little higher than that of the reverse osmosis water.5.The relationship among these trace elements in dialysis patients.In subjects with serum Sr level exceeding 100μg/L we found serum Al levels to be around 14.7±8.2μg/L,which was significantly lower compared to the overall mean serum Al level(P＜0.05).Although no significant difference was found in serum Ca levels between 'low Sr' and 'high Sr' groups(P=0.15),there was a remarkable tendency forwards lower serum Ca levels in the 'high Sr' groups.No correlation was found in dialysis patients between the blood Cd and Pb levels.Conclusions:1.The high prevalence of Cd exposure and low prevalence of Pb exposure is shown in chronic renal failure patients under study.After correcting the result of Pb and Cd for Hct,the prevalence of Cd and Pb exposure is significantly increased. So the correction of Pb and Cd levels for Hct may be recommended to allow objective comparison of both whole blood Pb and Cd levels in chronic renal failure patients.2.In the dialysis population under study blood Pb and Cd levels were closely related to the time on dialysis,whilst contamination of the dialysate may als0 contribute to the increased blood Cd and to a less extent Pb levels.3.A relatively high prevalence of Se deficiency is seen in the chronic renal failure patients under study.Within the HD populations serum Se levels can be determined by the patients' nutritional status.Moreover,the serum Se level tends to decrease with the time patients are on HD.A second factor may be a relatively low Se intake. moderately increased in dialysis patients.Increased serum Sr levels possibly ace associated with a Sr-rich diet whilst in the subset of dialysis patients the Sr content of the dialysate only seems to play a minor role.Significance:To the best of our knowledge,in the present study for the first time Pb,Cd,Se,Sr and Al levels were assessed in Chinese patients presenting different degrees of CRI as well as in post-transplant patients and hemodialysis patients and a possible relationship with clinical and personal factors was also deeply investigated.This study will help clinicians to understand changes in trace elements in renal failure patients in order to continue to study the role of these trace elements in the complication of hemodialysis.