Analysis of Cadmium, Mercury, and Lead Concentrations in Erythrocytes of Renal Transplant Recipients from Northwestern Poland

Cadmium (Cd), mercury (Hg), and lead (Pb) exhibit highly nephrotoxic properties, and their high concentrations can lead to renal failure. Much research has been conducted on the concentrations of heavy metals, microelements, and macroelements in the blood, but little is known about the concentration of Cd, Pb, and Hg in erythrocytes of renal recipients. The aim of this study is to determine the blood erythrocyte concentrations of toxic metals (Cd, Pb, and Hg) in renal transplant recipients (RTRs). Additionally, we analyzed the effect of selected biological and environmental factors, including the intake of various immunosuppressive drug regimens and smoking, on these xenobiotic concentrations. The material consisted of erythrocyte samples from 115 patients of the Department of Nephrology, Transplantology, and Internal Medicine at Independent Public Clinical Hospital No. 2, Pomeranian Medical University, Szczecin, in northwestern Poland. Cd, Hg, and Pb levels in the erythrocytes were quantified by inductively coupled mass spectroscopy (ICP-MS). Equal concentrations of Cd were found in erythrocytes of both female and male transplant recipients. The highest level of Hg was seen in women, and women overall had statistically higher concentrations of Pb than men. Comparison of metal concentrations between those over 50 years and those under it showed that Pb concentration was also significantly higher in renal transplant recipients over 50. Pb concentration was almost twice as high in RTRs who used tacrolimus with mycophenolate mofetil than in RTRs who used cyclosporine A with mycophenolate mofetil. The highest level of Cd was seen in smokers, who had 3.25 µg/L. This value was significantly higher than in ex-smokers (p = 0.001) and with RTRs who had never smoked. There were significantly higher levels of Pb in the erythrocytes of RTRs who were ex-smokers than in those who had never smoked. A statistically significant correlation was found between Cd and Pb concentrations. Additionally, we have noticed significant positive correlation between Pb and age (R = 0.37), gender (R = 0.24) and significant negative correlation of Pb with GFR (R = −0.33). We have also found significant positive correlation between Hg and age (R = 0.21). In summary, our data suggest that, smoking is associated with Pb and Cd concentrations, and gender, age change depending on Pb concentration in erythrocytes of RTRs. Additionally, this is the first research that suggests that immunosuppressive regimen, depending on type of immunosuppressive drugs combination affects Pb concentration in erythrocytes of RTRs. It seems to be crucial information for patients who use immunosuppressive drugs.

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Serum Selenium, Iron, Zinc, and Copper Concentrations in Renal Transplant Recipients Treated with Mycophenolate Mofetil

Biological Trace Element Research ◽

10.1007/s12011-020-02074-2 ◽

2020 ◽

Vol 198 (2) ◽

pp. 371-379 ◽

Cited By ~ 1

Author(s):

Aleksandra Wilk ◽

Dagmara Szypulska-Koziarska ◽

Małgorzata Marchelek-Myśliwiec ◽

Wojciech Głazek ◽

Barbara Wiszniewska

Keyword(s):

Trace Elements ◽

Mycophenolate Mofetil ◽

Renal Transplant ◽

Immunosuppressive Drugs ◽

Normal Function ◽

Serum Selenium ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Inductively Coupled ◽

Cu And Zn

Abstract There are data available in the literature on bioelement concentrations in the serum of various groups of patients; however, very little is known about the serum concentration of selenium (Se), iron (Fe), zinc (Zn), and copper (Cu) in renal transplant patients treated with immunosuppressive drugs, including mycophenolate mofetil (MMF). Monitoring of serum bioelement concentrations in renal transplant recipients is of profound importance, as the proper bioelement levels seem to prolong the normal function of the transplanted organ. Thus, the aim of this current study was to examine and carry out comparative analysis involving serum concentrations of Se, Fe, Cu, and Zn of renal transplant recipients treated with MMF and without MMF. The material consisted of blood samples from 115 patients of the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University, in the city of Szczecin in the northwestern Poland. Serum Se, Fe, Cu, and Zn levels were quantified by inductively coupled mass spectroscopy (ICP-MS). Taking into account all patients, MMF increases Cu level. Cu and Fe concentrations were significantly higher in women treated with MMF; in group of younger patients treated with MMF, Se level was significantly lower comparing with those whose regimen did not include MMF. Additionally, MMF in combination with prednisone increased Se concentration in blood of transplant recipients. Our study highlights that trace elements should be monitored to allow for an early detection of trace elements deficits, which can easily be corrected for by an adjusted diet or supplemental intake.

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Arsenic and Selenium Profile in Erythrocytes of Renal Transplant Recipients

Biological Trace Element Research ◽

10.1007/s12011-019-02021-w ◽

2019 ◽

Vol 197 (2) ◽

pp. 421-430 ◽

Cited By ~ 1

Author(s):

Aleksandra Wilk ◽

Barbara Wiszniewska

Keyword(s):

Mycophenolate Mofetil ◽

Renal Transplant ◽

Chemical Elements ◽

Immunosuppressive Treatment ◽

Selenium Concentration ◽

Immunosuppressive Drugs ◽

International Agency ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Inductively Coupled

AbstractArsenic and selenium elements play extremely important roles in organisms. Too high As concentration in blood may lead to functional disorders within organs, including cancer. Arsenic is designated as a Group 1 human carcinogen by the International Agency for Research on Cancer that has established causal role of arsenic in cancers of the urinary bladder, lung, and skin in humans. In contrast, Se is believed to be the antioxidant trace element that is important in the biological defense against oxidative damage. We tested the hypothesis that immunosuppressive treatment based on mycophenolate mofetil (MMF), that is one of the most commonly used drug by renal transplant recipients, affects arsenic and selenium concentration in erythrocytes of renal transplant recipients. Current research was undertaken due to the fact that there are few studies on the concentration of chemical elements in the erythrocytes in kidney patients receiving immunosuppressive drugs. Monitoring of the concentration of chemical elements in the blood in patients who underwent kidney transplantation could be helpful, since chemical elements play an important role in many biological processes and it seems to be crucial in the prevention of cancer to which renal transplant recipients are more often exposed.The material consisted of blood from 115 renal transplant recipients of the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University, in the city of Szczecin in northwestern Poland. Arsenic and selenium levels in erythrocytes were quantified by inductively coupled mass spectroscopy.Men MMF+ had significantly higher As concentration than men MMF−. Se concentration was significantly higher in younger patients compared with older patients. The patients with lower creatinine level who used MMF had significantly higher As than MMF− patients. Patients whose therapy was based on MMF, cyclosporine A and glucocorticosteroids exhibited significantly higher concentration of As compared with patients whose regimen was based on MMF, tacrolimus, and glucocorticosteroids.This is the first study that demonstrates that regimen based on mycophenolate mofetil affects As and Se concentrations in erythrocytes in renal transplant recipients.

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Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients

Journal of Clinical Medicine ◽

10.3390/jcm9020386 ◽

2020 ◽

Vol 9 (2) ◽

pp. 386 ◽

Cited By ~ 8

Author(s):

J. Casper Swarte ◽

Rianne M. Douwes ◽

Shixian Hu ◽

Arnau Vich Vila ◽

Michele F. Eisenga ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Renal Transplant ◽

Gut Microbiome ◽

Linear Models ◽

Immunosuppressive Drugs ◽

Renal Transplant Recipients ◽

Healthy Controls ◽

Transplant Recipients ◽

Microbiome Composition ◽

Intestinal Dysbiosis

Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5–12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome.

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Relationship of transitional regulatory B and regulatory T cells and immunosuppressive drug doses in stable renal transplant recipients

Immunity Inflammation and Disease ◽

10.1002/iid3.473 ◽

2021 ◽

Author(s):

Eman H Ibrahim ◽

Mostafa Aly ◽

Christian Morath ◽

Douaa M Sayed ◽

Naruemol Ekpoom ◽

...

Keyword(s):

T Cells ◽

Renal Transplant ◽

Regulatory T Cells ◽

Immunosuppressive Drug ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Drug Doses ◽

Relationship Of

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Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients

BMC Nephrology ◽

10.1186/s12882-021-02374-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Eman H. Ibrahim ◽

Mostafa G. Aly ◽

Gerhard Opelz ◽

Christian Morath ◽

Martin Zeier ◽

...

Keyword(s):

Renal Transplant ◽

B Cell ◽

Graft Function ◽

Cell Subset ◽

Immunosuppressive Drugs ◽

Renal Transplant Recipients ◽

Healthy Controls ◽

Transplant Recipients ◽

Significant Positive Association ◽

Ifn Γ

Abstract Background The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups. Method Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ. Results ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015). Conclusions Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

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