scholarly journals The Microbiota and Kidney Transplantation: Influence on the Graft

EMJ Urology ◽  
2021 ◽  
pp. 95-105
Author(s):  
Maurizio Salvadori ◽  
Aris Tsalouchos

The gut microbial community may be associated with complications after kidney transplantation. The indigenous microbiota has a significant and protective function that influences the transplant recipient response. Genetic or environmental factors may modify the indigenous microbiota and pathobionts appear. In this condition, several disturbances of the kidney graft may be observed. These include acute rejection, infection, diarrhoea, disturbance in the induction of tolerance, and modification of immunosuppressive drug metabolism. Recently, the use of prebiotics, probiotics, and synbiotics has been demonstrated to be effective in normalising these conditions and in restoring the generation of the normal indigenous microbiota. An improved understanding of the function and composition of the indigenous microbiota may help in finding further solutions to stabilise the microbiota after kidney transplantation.

2016 ◽  
Vol 283 (1831) ◽  
pp. 20160312 ◽  
Author(s):  
Kathrin Näpflin ◽  
Paul Schmid-Hempel

Microbial communities are a key component of host health. As the microbiota is initially ‘foreign’ to a host, the host's immune system should respond to its acquisition. Such variation in the response should relate not only to host genetic background, but also to differences in the beneficial properties of the microbiota. However, little is known about such interactions. Here, we investigate the gut microbiota of the bumblebee, Bombus terrestris , which has a protective function against the bee's natural trypanosome gut parasite, Crithidia bombi . We transplanted ‘resistant’ and ‘susceptible’ microbiota into ‘resistant’ and ‘susceptible’ host backgrounds, and studied the activity of the host immune system. We found that bees from different resistance backgrounds receiving a microbiota differed in aspects of their immune response. At the same time, the elicited immune response also depended on the received microbiota's resistance phenotype. Furthermore, the microbial community composition differed between microbiota resistance phenotypes (resistant versus susceptible). Our results underline the complex feedback between the host's ability to potentially exert selection on the establishment of a microbial community and the influence of the microbial community on the host immune response in turn.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hengcheng Zhang ◽  
Zijie Wang ◽  
Jiayi Zhang ◽  
Zeping Gui ◽  
Zhijian Han ◽  
...  

BackgroundCostimulatory blockade provides new therapeutic opportunities for ensuring the long-term survival of kidney grafts. The adoption of the novel immunosuppressant Belatacept has been limited, partly due to concerns regarding higher rates and grades of acute rejection in clinical trials. In this study, we hypothesized that a combined therapy, Belatacept combined with BTLA overexpression, may effectively attenuate acute rejection after kidney transplantation.Materials and MethodsThe rat kidney transplantation model was used to investigate graft rejection in single and combined therapy. Graft function was analyzed by detecting serum creatinine. Pathological staining was used to observe histological changes in grafts. The expression of T cells was observed by immunohistochemistry and flow cytometry. In vitro, we constructed an antigen-stimulated immune response by mixed lymphocyte culture, treated with or without Belatacept and BTLA-overexpression adenovirus, to observe the proliferation of receptor cells and the expression of cytokines. In addition, western blot and qRT-PCR analyses were performed to evaluate the expression of CTLA-4 and BTLA at various time points during the immune response.ResultsIn rat models, combined therapy reduced the serum creatinine levels and prolonged graft survival compared to single therapy and control groups. Mixed acute rejection was shown in the allogeneic group and inhibited by combination treatment. Belatacept reduced the production of DSA and the deposition of C4d in grafts. Belatacept combined with BTLA overexpression downregulated the secretion of IL-2 and IFN-γ, as well as increasing IL-4 and IL-10 expression. We also found that Belatacept combined with BTLA overexpression inhibited the proliferation of spleen lymphocytes. The duration of the elevated expression levels of CTLA-4 and BTLA differentially affected the immune response.ConclusionBelatacept combined with BTLA overexpression attenuated acute rejection after kidney transplantation and prolonged kidney graft survival, which suggests a new approach for the optimization of early immunosuppression after kidney transplantation.


2020 ◽  
Vol 104 (S3) ◽  
pp. S342-S342
Author(s):  
Hengcheng Zhang ◽  
Hao Chen ◽  
Li Sun ◽  
Zijie Wang ◽  
Zhijian Han ◽  
...  

2009 ◽  
Vol 77 (6) ◽  
pp. 2367-2375 ◽  
Author(s):  
Dionysios A. Antonopoulos ◽  
Susan M. Huse ◽  
Hilary G. Morrison ◽  
Thomas M. Schmidt ◽  
Mitchell L. Sogin ◽  
...  

ABSTRACT Shifts in microbial communities are implicated in the pathogenesis of a number of gastrointestinal diseases, but we have limited understanding of the mechanisms that lead to altered community structures. One difficulty with studying these mechanisms in human subjects is the inherent baseline variability of the microbiota in different individuals. In an effort to overcome this baseline variability, we employed a mouse model to control the host genotype, diet, and other possible influences on the microbiota. This allowed us to determine whether the indigenous microbiota in such mice had a stable baseline community structure and whether this community exhibited a consistent response following antibiotic administration. We employed a tag-sequencing strategy targeting the V6 hypervariable region of the bacterial small-subunit (16S) rRNA combined with massively parallel sequencing to determine the community structure of the gut microbiota. Inbred mice in a controlled environment harbored a reproducible baseline community that was significantly impacted by antibiotic administration. The ability of the gut microbial community to recover to baseline following the cessation of antibiotic administration differed according to the antibiotic regimen administered. Severe antibiotic pressure resulted in reproducible, long-lasting alterations in the gut microbial community, including a decrease in overall diversity. The finding of stereotypic responses of the indigenous microbiota to ecologic stress suggests that a better understanding of the factors that govern community structure could lead to strategies for the intentional manipulation of this ecosystem so as to preserve or restore a healthy microbiota.


2014 ◽  
Vol 98 (7) ◽  
pp. 697-705 ◽  
Author(s):  
John R. Lee ◽  
Thangamani Muthukumar ◽  
Darshana Dadhania ◽  
Nora C. Toussaint ◽  
Lilan Ling ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ulrich Jehn ◽  
Katharina Schütte-Nütgen ◽  
Joachim Bautz ◽  
Hermann Pavenstädt ◽  
Barbara Suwelack ◽  
...  

AbstractBK polyomavirus (BKPyV) and cytomegalovirus (CMV) are the main viral pathogens affecting the graft and recipient outcome after allogenic kidney transplantation. It has recently been found that infection with both viruses has a greater impact on kidney graft function than a single infection. We retrospectively analyzed a cohort of 723 recipients who received kidney transplantation between 2007 and 2015 after living and postmortal donation for differences in risk and outcome parameters regarding BKPyV (DNAemia) and CMV (CMV DNAemia) co-infection compared to sole viremias and to patients without viremia. Of all kidney allograft recipients in our cohort, 8.2% developed co-infection with BKPyV DNAemia and CMV DNAemia, 15.1% showed BKPyV viremia alone and 25.2% sole CMV DNAemia. Acute rejection was closely linked with co-infection (multivariable analysis, p = 0.001). Despite the fact that the estimated glomerular filtration rate of patients with co-infection was noticeably reduced compared to patients with BKV or CMV infection alone, transplant survival and patient survival were not significantly reduced. Co-infection with BKPyV and CMV in kidney transplanted patients is significantly associated with inferior allograft function. Since co-infection is strongly associated with acute rejection, co-infected individuals should be considered a risk collective.


2020 ◽  
Vol 21 (16) ◽  
pp. 5616
Author(s):  
Koen E. Groeneweg ◽  
Jacques M.G.J. Duijs ◽  
Barend W. Florijn ◽  
Cees van Kooten ◽  
Johan W. de Fijter ◽  
...  

Acute rejection (AR) of a kidney graft in renal transplant recipients is associated with microvascular injury in graft dysfunction and, ultimately, graft failure. Circulating long noncoding RNAs (lncRNAs) may be suitable markers for vascular injury in the context of AR. Here, we first investigated the effect of AR after kidney transplantation on local vascular integrity and demonstrated that the capillary density markedly decreased in AR kidney biopsies compared to pre-transplant biopsies. Subsequently, we assessed the circulating levels of four lncRNAs (LNC-RPS24, LNC-EPHA6, MALAT1, and LIPCAR), that were previously demonstrated to associate with vascular injury in a cohort of kidney recipients with a stable kidney transplant function (n = 32) and recipients with AR (n = 15). The latter were followed longitudinally six and 12 months after rejection. We found higher levels of circulating LNC-EPHA6 during rejection, compared with renal recipients with a stable kidney function (p = 0.017), that normalized one year after AR. In addition, LNC-RPS24, LNC-EPHA6, and LIPCAR levels correlated significantly with the vascular injury marker soluble thrombomodulin. We conclude that AR and microvascular injury are associated with higher levels of circulating LNC-EPHA6, which emphasizes the potential role of lncRNAs as biomarker in the context of AR.


2013 ◽  
Vol 131 (3) ◽  
pp. 205-207 ◽  
Author(s):  
Bo-Ra Kim ◽  
Ho-Sik Shin ◽  
Yeon-Soon Jung ◽  
Hark Rim

CONTEXT Tacrolimus is a potent immunosuppressive drug often administered to transplant recipient patients and exhibits a variety of adverse cardiovascular effects. CASE REPORT We report a case of a 53-year-old Asian female who developed various arrhythmic phenomena including atrial premature complexes and supraventricular tachycardia after administration of tacrolimus. CONCLUSION Tacrolimus-associated arrhythmia after kidney transplantation may be life-threatening, and so patients undergoing this procedure should be carefully monitored.


Author(s):  
A. V. Pinchuk ◽  
N. V. Shmarina ◽  
I. V. Dmitriev ◽  
E. S. Stolyarevich ◽  
N. V. Natalya V. Zagorodnikova ◽  
...  

Introduction. Despite the improvements in immunosuppressive therapy, the growing number of repeat kidney transplantations and associated risks of acute rejection make it relevant to assess the impact of early acute rejection on a long-term kidney graft survival.Objective. The aim of the study was to evaluate the rate, the clinical aspects of early acute rejection after repeat kidney transplantation and the outcomes of its treatment, to perform the assessment of the impact of rejection episodes on a long-term kidney graft survival.Material and methods. We carried out the retrospective analysis of kidney graft survival after 121 repeat kidney transplantations performed in N.V. Sklifosovsky Research Institute for Emergency Medicine in the period from 2007 to 2018. Group I included 96 recipients after kidney transplantation without acute rejection in postoperative period. Group II consisted of 25 patients with early acute rejection after kidney transplantation. We performed the assessment of the impact of early acute rejection on the kidney graft survival in comparison with recipients with uncomplicated postoperative period. Statistical processing was carried out by nonparametric methods. Survival was assessed using the Kaplan–Meier curves.Results. 1-year and 3-year kidney graft survival rates amounted to 90.3% (95%, confidence interval 85–95) and 85.4% (95%, CI 79–91), respectively, in recipients of Group I; and 72% (95%, CI 58–86) and 60% (95%, CI 46–76) in patients of Group II. Significant differences in 1-year and 3-year kidney graft survival between patients of Group I and II have been noticed (P=0.0022 and P=0.0065, respectively).Conclusions. Patients with early acute rejection after kidney transplantation had poorer kidney graft survival in comparison with patients without rejection episodes in postoperative period.


2004 ◽  
Vol 171 (4S) ◽  
pp. 494-494
Author(s):  
Michio Michio Nojima ◽  
Tetsuro Yoshimoto ◽  
Atsushi Nakao ◽  
Takuo Maruyama ◽  
Hidekazu Takiuchi ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document