Acute Rejection and Infectious Complications in ABO- and HLA-Incompatible Kidney Transplantations

Kim, Jee Yeon; Kim, Sung-Han; Kim, Dong Hyun; Lim, Seong Jun; Shin, Sung; Kim, Young Hoon; Jung, Joohee; Park, Su-Kil; Kwon, Hyunwook; Han, Duck Jong

doi:10.12659/aot.927420

Cited by 7 publications

(14 citation statements)

References 41 publications

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“…These findings are in parallel with several other studies [23,[29][30][31]. Moreover, age, HLA-incompatible transplantation, and a higher number of HLA mismatches were associated with rejection after transplantation, in agreement with results from previous reports [32][33][34]. Our study indicated that episodes of viral or nonviral infection requiring hospitalization were associated with older age, deceased rather than living donors, female sex, HLA-incompatible and ABO-incompatible kidney transplantation, and ATG rather than basiliximab induction, in accordance with previous studies [32,33,[35][36][37].…”

Section: Discussionsupporting

confidence: 93%

“…Moreover, age, HLA-incompatible transplantation, and a higher number of HLA mismatches were associated with rejection after transplantation, in agreement with results from previous reports [32][33][34]. Our study indicated that episodes of viral or nonviral infection requiring hospitalization were associated with older age, deceased rather than living donors, female sex, HLA-incompatible and ABO-incompatible kidney transplantation, and ATG rather than basiliximab induction, in accordance with previous studies [32,33,[35][36][37]. Because a compromised capacity to repair injury in older kidneys could lead to accelerated immune response and acute rejection, the risks of rejection might be higher in older donor kidney transplantation [38].…”

Section: Discussionsupporting

confidence: 92%

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The Korean Organ Transplantation Registry (KOTRY): an overview and summary of the kidney-transplant cohort

Jeon

Koo²,

et al. 2022

Kidney Res Clin Pract

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Background: As the need for a nationwide organ-transplant registry emerged, a prospective registry, the Korean Organ Transplantation Registry (KOTRY), was initiated in 2014. Here, we present baseline characteristics and outcomes of the kidney-transplant cohort for 2014 through 2019. Methods: The KOTRY consists of five organ-transplant cohorts (kidney, liver, lung, heart, and pancreas). Data and samples were prospectively collected from transplant recipients and donors at baseline and follow-up visits; and epidemiological trends, allograft outcomes, and patient outcomes, such as posttransplant complications, comorbidities, and mortality, were analyzed. Results: From 2014 to 2019, there were a total of 6,129 registered kidney transplants (64.8% with living donors and 35.2% with deceased donors) with a mean recipient age of 49.4 ± 11.5 years, and 59.7% were male. ABO-incompatible transplants totaled 17.4% of all transplants, and 15.0% of transplants were preemptive. The overall 1- and 5-year patient survival rates were 98.4% and 95.8%, respectively, and the 1- and 5-year graft survival rates were 97.1% and 90.5%, respectively. During a mean follow-up of 3.8 years, biopsy- proven acute rejection episodes occurred in 17.0% of cases. The mean age of donors was 47.3 ± 12.9 years, and 52.6% were male. Among living donors, the largest category of donors was spouses, while, among deceased donors, 31.2% were expanded-criteria donors. The mean serum creatinine concentrations of living donors were 0.78 ± 0.62 mg/dL and 1.09 ± 0.24 mg/dL at baseline and 1 year after kidney transplantation, respectively. Conclusion: The KOTRY, a systematic Korean transplant cohort, can serve as a valuable epidemiological database of Korean kidney transplants.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

The Korean Organ Transplantation Registry (KOTRY): an overview and summary of the kidney-transplant cohort

Jeon

Koo²,

et al. 2022

Kidney Res Clin Pract

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“…CD226 downregulation and high levels of TIGIT were previously described in cancer and chronic viral infections 19 – 21 . In the same way, we previously found in highly immunosuppressed HLA incompatible kidney transplant recipients known to present a high risk of infectious complications 43 , higher levels of TIGIT expression, compared to ABO-incompatible recipients 25 . TIGIT was also previously identified in kidney biopsies as one of the most specific transcript changes (with other costimulation -related transcript) during pure T-cell mediated rejection, compared with other disease 44 .…”

Section: Discussionsupporting

confidence: 72%

The CD226/TIGIT axis is involved in T cell hypo-responsiveness appearance in long-term kidney transplant recipients

Bello

Gouin

Chaubet

et al. 2022

Sci Rep

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T cell exhaustion refers to a dysfunctional state in which effector T cells present a decreased ability to proliferate and to produce cytokines, while the co-expression of inhibitory receptors increases. We investigated global and donor-specific T cell responses in a cohort of stable, living-donor kidney transplant patients that received similar immunosuppression. After transplantation, an increase in the ratio of TIGIT + /CD226 + in mCD4 + T cells (r = 0.47, p = 0.01), and a decrease of CD226 + TIGIT-mCD4 + T cells was observed (r = − 0.55, p = 0.001). This leads to an increase of dysfunctional T cells in patients far from transplantation. In mCD8 + T cells, a decrease of IL-2 production after mitogenic stimulation was observed far from transplantation. Phenotypic analyses revealed an increase of mCD8 + T cells co-expressing PD-1 and TIGIT over time (r = 0.51, p = 0.02). After donor-specific stimulation, the ability of CD4 + T cells to proliferate was decreased compared with third parties. CD4 + T cells expressing CD226 and TIGIT were correlated with allospecific CD4 + proliferation (r = 0.68, p = 0.04). Our study suggests that after kidney transplantation a T cell hyporesponsiveness appears over time, driven by a dysregulation of CD226/TIGIT axis in mCD4 + T cells, associated with an increase of PD1 + TIGIT + in mCD8 + T cells.

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“…Among them, HLA (human leukocyte antigen) is known to be the expression product of human major histocompatibility complex (MHC). The mismatch of HLA is a risk factor to affect kidney allograft function and to increase the chance of rejection [ 31 – 33 ]. For example, Ko et al investigated the clinical outcome of kidney transplantation with ABO and HLA incompatibilities.…”

Section: Resultsmentioning

confidence: 99%

“…For example, Ko et al investigated the clinical outcome of kidney transplantation with ABO and HLA incompatibilities. The result found that ABO and HLA incompatibilities could increase the probability of infection-medicated rejection and influence the overall survival both for patient and graft [ 31 ]. Moreover, HLA donor-specific antibodies could induce inflammation, vessel injury and AMR by binding to vascular endothelial cells of the allograft [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

Multi-omics network characterization reveals novel microRNA biomarkers and mechanisms for diagnosis and subtyping of kidney transplant rejection

Lin

Wang

et al. 2021

J Transl Med

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Background Kidney transplantation is an optimal method for treatment of end-stage kidney failure. However, kidney transplant rejection (KTR) is commonly observed to have negative effects on allograft function. MicroRNAs (miRNAs) are small non-coding RNAs with regulatory role in KTR genesis, the identification of miRNA biomarkers for accurate diagnosis and subtyping of KTR is therefore of clinical significance for active intervention and personalized therapy. Methods In this study, an integrative bioinformatics model was developed based on multi-omics network characterization for miRNA biomarker discovery in KTR. Compared with existed methods, the topological importance of miRNA targets was prioritized based on cross-level miRNA-mRNA and protein–protein interaction network analyses. The biomarker potential of identified miRNAs was computationally validated and explored by receiver-operating characteristic (ROC) evaluation and integrated “miRNA-gene-pathway” pathogenic survey. Results Three miRNAs, i.e., miR-145-5p, miR-155-5p, and miR-23b-3p, were screened as putative biomarkers for KTR monitoring. Among them, miR-155-5p was a previously reported signature in KTR, whereas the remaining two were novel candidates both for KTR diagnosis and subtyping. The ROC analysis convinced the power of identified miRNAs as single and combined biomarkers for KTR prediction in kidney tissue and blood samples. Functional analyses, including the latent crosstalk among HLA-related genes, immune signaling pathways and identified miRNAs, provided new insights of these miRNAs in KTR pathogenesis. Conclusions A network-based bioinformatics approach was proposed and applied to identify candidate miRNA biomarkers for KTR study. Biological and clinical validations are further needed for translational applications of the findings.

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Acute Rejection and Infectious Complications in ABO- and HLA-Incompatible Kidney Transplantations

Cited by 7 publications

References 41 publications

The Korean Organ Transplantation Registry (KOTRY): an overview and summary of the kidney-transplant cohort

The Korean Organ Transplantation Registry (KOTRY): an overview and summary of the kidney-transplant cohort

The CD226/TIGIT axis is involved in T cell hypo-responsiveness appearance in long-term kidney transplant recipients

Multi-omics network characterization reveals novel microRNA biomarkers and mechanisms for diagnosis and subtyping of kidney transplant rejection

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