scholarly journals The association of two single-nucleotide polymorphisms of the FOXP3 gene (rs3761548 and rs3761547) with renal allograft function and survival in kidney transplant recipients

2020 ◽  
Vol 7 (2) ◽  
pp. e21-e21
Author(s):  
Vahideh Ebrahimzadeh Attari ◽  
Seyed Sadroddin Rasi Hashemi ◽  
Solmaz Oloufi ◽  
Leili Aghebati Maleki ◽  
Dariush Shanehbandi ◽  
...  

Introduction: The FOXP3 protein is an immune regulatory protein that specifically maintains the function and differentiation of regulatory T cells (Tregs) and prevents autoimmunity. Variations in FOXP3 gene may alter its function and also the immune response. Objectives: The present study was conducted to investigate the association of the FOXP3 gene polymorphisms -3499 A/G and -3279 A/C with renal allograft function and survival in kidney transplant recipients. Patients and Methods: In this cross-sectional study, 150 eligible kidney transplant recipients were evaluated. Kidney function was evaluated at three- and five-year post-transplant using serum creatinine level and glomerular filtration rate as indicators. Genotyping of the study participants was performed using the PCR– restriction fragment length polymorphism method. Results: The frequencies of AA, AG, and GG genotypes of the -3499 A/G polymorphism were 62.42%, 29.53%, and 8.05%, respectively. For the -3279 A/C polymorphism, the frequencies of the AA, AC, and CC genotypes were 21.33%, 32%, and 46.67%, respectively. The mean ± SD of serum creatinine level, three and five years after transplantation were 1.70 ± 1.58 and 1.87 ± 1.94, respectively. Serum creatinine level and kidney function did not show any significant association with these polymorphisms. Conclusion: In the present study, only 10% of participants experienced episodes of severe kidney dysfunction and we did not find any significant association between kidney function and the subjects’ genotypes. Further epidemiologic studies with greater sample sizes may be needed to clarify this association.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas Duflot ◽  
Charlotte Laurent ◽  
Anne Soudey ◽  
Xavier Fonrose ◽  
Mouad Hamzaoui ◽  
...  

AbstractThis study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia–reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252979
Author(s):  
Skylar L. Nahi ◽  
Aneesha A. Shetty ◽  
Sajal D. Tanna ◽  
Joseph R. Leventhal

Background Kidney transplant recipients are a unique cohort in regard to SARS-CoV 2 susceptibility and clinical course, owing to their immunosuppressed state and propensity for kidney injury. The primary purpose of this study is to ascertain if, in kidney transplant recipients, SARS-CoV 2 infection impacts long term renal allograft function. Methods This retrospective, single-center study reviewed 53 kidney transplant recipients with a positive SARS-CoV-2 PCR at NMH from January 1, 2020 to June 30, 2020. Results Change in eGFR from baseline kidney function prior to infection to 90 days after the first positive SARS-CoV 2 test was +1.76%, -17.5% and -23.16% the mild, moderate and severe disease groups respectively. There was a significant decline in kidney function in the moderate and severe disease cohorts as compared to the mild disease cohort, with respective p values of p = 0.0002 and p = 0.021. Relative to the mild disease cohort, the moderate and severe disease cohorts also demonstrated significantly increased risk of developing AKI (66%, 85%), both with p values of P = 0.0001. Conclusions Clinically severe SARS-CoV 2 infection is associated with greater risk of acute kidney injury and greater decline in renal allograft function at 90 days post infection, compared to mild disease.


2019 ◽  
Vol 9 (3) ◽  
pp. e24-e24
Author(s):  
Vahideh Ebrahimzadeh Attari ◽  
Zahra Shahvegharasl ◽  
Pouya Fathalizadeh ◽  
Sajjad Pourasghary ◽  
Mohammadali Mohajel Shoja ◽  
...  

Introduction: Kidney transplantation has considerably increased the survival and life quality of patients with end-stage renal disease. Objectives: The current study was designed to investigate the circulating level of dephosphorylateduncarboxylated matrix gamma carboxyglutamate protein (dp-ucMGP) as a marker of vitamin K status and vascular calcification in kidney transplant recipients as well as its association with the allograft function. Patients and Methods: In this cross-sectional study, 90 eligible kidney transplant recipients were evaluated in the post-transplant phase (about 6-12 months after kidney transplantation). The serum levels of dp-ucMGP, urea, creatinine and other biochemical indices were determined. Results: The mean serum level of dp-ucMGP was 3.78±3.79 µg/L. Most of the participants (80%) had a normal range of serum dp-ucMGP (<4 µg/L). However, 10 % had high serum dp-ucMGP (>12 µg/L). Serum dp-ucMGP did not have any statistical significant association with serum urea, creatinine and kidney function (P>0.05). Conclusion: Further epidemiologic studies are needed to assess the time trends of dp-ucMGP after renal transplant and its relation to kidney function, since high serum level of dp-ucMGP may make kidney transplant recipients prone to various cardiovascular disease (CVD) and transplant rejection.


2021 ◽  
Author(s):  
Divya Bajpai ◽  
Satarupa Deb ◽  
Sreyashi Bose ◽  
Chintan Gandhi ◽  
Tulsi Modi ◽  
...  

2018 ◽  
Vol 19 (12) ◽  
pp. 3945 ◽  
Author(s):  
Monika Lindemann ◽  
Johannes Korth ◽  
Ming Sun ◽  
Shilei Xu ◽  
Christoph Struve ◽  
...  

In kidney transplant recipients, the cytomegalovirus (CMV) is frequently causing infection/reactivation and can trigger allograft rejection. To assess the risk of reactivation, the cellular immune response against CMV is increasingly assessed by cellular in vitro methods, such as the interferon (IFN)-γ ELISpot. In the current study we compared the IFN-γ ELISpot with our newly established CMV-specific ELISpot assays determining IL-17A, IL-21, IL-22, granzyme B, and perforin and correlated the results with flow cytometric data and clinical parameters. In 77 kidney transplant recipients, the highest frequency was observed for CMV pp65-specific cells secreting IFN-γ, followed by cells secreting IL-21 (62.9 and 23.2 Δ spot forming cells/105 cells). We observed a positive correlation between the percentage of CMV-specific CD3+ CD4+ CD154+ cells and results of the CMV-specific IL-21 ELISpot (p = 0.002). Results of the CMV pp65-specific IL-21 ELISpot correlated negatively with kidney function (estimated glomerular filtration rate, p = 0.006) and were significantly higher in women (p = 0.005). IL-21, a cytokine involved in aging that is secreted by activated CD4+ T cells, may also impact on allograft function. Thus, the CMV-specific IL-21 ELISpot could become a new tool to assess if CMV seropositivity represents a hazard for the graft.


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