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The Immunology and Clinical Outcome of Renal Transplantation
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The Immunology and Clinical Outcome of Renal Transplantation

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (11 October 2022) | Viewed by 12417

Special Issue Editor

Dr. Manuel Muro

E-Mail Website
Guest Editor
1. Head of Immunology Service and Director of Regional Laboratory of Histocompatibility and Transplant Immunology, Clinical University Hospital “Virgen de la Arrixaca”, El Palmar, Murcia, Spain
2. Biomedical Research Institute of Murcia (IMIB), Murcia, Spain
Interests: transplant immunology; tolerance; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

With the exception of dialysis, kidney transplantation is the treatment of choice for chronic kidney failure. The short-term results of kidney transplantation are usually excellent; by contrast, there is scope for relative improvement in long-term results, with a relevant role for anti-donor specific antibodies (DSA). The great advancements in immunosuppression and detection techniques for these DSA antibodies has reduced the incidence of acute rejection to below 10%, but it is chronic kidney graft dysfunction that is really limiting for optimal long-term evolution and is mediated mainly by immunological mechanisms that subvert tolerance to the graft. The great advances in understanding of the diagnosis of the immune response of T, B, NK, and regulatory cells has led to the development of new immunomodulatory therapies that seek to prolong graft survival, including those that seek to reduce the production of harmful antibodies and those that seek to eliminate circulating antibodies in the event of a humoral rejection.

For this Special Issue, we hope to encourage submissions that discuss the current state of the art, addressing ongoing knowledge gaps and focusing on ongoing controversies related to immunology and clinical outcomes of renal transplantation, transplant immunology, tolerance, immunoregulatory pathways, organ preservation, graft function, sensitization, advances in immune suppression, treatments for rejection or pre- and post-transplant renal diseases. or predisposition to renal insufficiency. Contributions in the form of original articles are welcome, as are translational research papers.

Dr. Manuel Muro
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Immunology of renal transplantation
  • Immunoregulatory pathways
  • Advances in immunosuppression
  • Sensitization and donor-specific antibody (DSA) detection
  • Injury and renal graft function
  • Treatments for graft rejection
  • Renal diseases
  • Tolerance
  • Biomarkers in renal transplantation

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Published Papers (5 papers)

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Research

15 pages, 10530 KiB  
Article
Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers
by Almas Nuchjumroon, Somratai Vadcharavivad, Wanchana Singhan, Manorom Poosoonthornsri, Wiwat Chancharoenthana, Suwasin Udomkarnjananun, Natavudh Townamchai, Yingyos Avihingsanon, Kearkiat Praditpornsilpa and Somchai Eiam-Ong
J. Clin. Med. 2022, 11(21), 6320; https://doi.org/10.3390/jcm11216320 - 26 Oct 2022
Cited by 6 | Viewed by 2154
Abstract
A high intra-patient variability (IPV) of tacrolimus exposure is associated with poor long-term kidney transplantation outcomes. To assess the influence of cytochrome P450 (CYP) 3A5 genetic polymorphisms on tacrolimus IPV, 188 clinically stable kidney transplant recipients, who had received an immediate-release tacrolimus-based immunosuppressive regimen, [...] Read more.
A high intra-patient variability (IPV) of tacrolimus exposure is associated with poor long-term kidney transplantation outcomes. To assess the influence of cytochrome P450 (CYP) 3A5 genetic polymorphisms on tacrolimus IPV, 188 clinically stable kidney transplant recipients, who had received an immediate-release tacrolimus-based immunosuppressive regimen, were enrolled in this retrospective cohort study. Genotyping of CYP3A5*3 (rs776746) was performed and 110 (58.5%) were identified as CYP3A5 expressers and 78 (41.5%) as nonexpressers. Whole blood tacrolimus concentrations were analyzed by chemiluminescent microparticle immunoassay. Dose-adjusted trough tacrolimus concentrations (C0/D) measured at months 6, 9, and 12 were used to determine IPV. There were no significant differences in the IPV estimated by the coefficient of variation, the IPV calculated by mean absolute deviation method, and the proportions of recipients with the IPV estimated by the coefficient of variation of 30% or more between CYP3A5 expressers and nonexpressers (p = 0.613, 0.686, and 0.954, respectively). Tacrolimus C0/D in CYP3A5 expressers was approximately half of those in nonexpressers, overall (p < 0.001). In both CYP3A5 expressers and nonexpressers, tacrolimus C0/D increased gradually from month 6 to month 12 (p = 0.021). There was no evidence that the CYP3A5 polymorphisms significantly influence tacrolimus IPV during the 6 to 12 months after kidney transplantation. Full article
(This article belongs to the Special Issue The Immunology and Clinical Outcome of Renal Transplantation)
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10 pages, 820 KiB  
Article
Decrease in CD14++CD16+ Monocytes in Low-Immunological-Risk Kidney Transplant Patients with Subclinical Borderline Inflammation
by Abelardo Caballero, Teresa Vazquez-Sanchez, Pedro Ruiz-Esteban, Myriam Leon, Juana Alonso-Titos, Veronica Lopez, Eugenia Sola, Elena Gutierrez, Mercedes Cabello, Cristina Casas-Gonzalez, Rafael Pozo-Alvarez, Juan Delgado-Burgos and Domingo Hernandez
J. Clin. Med. 2021, 10(21), 5051; https://doi.org/10.3390/jcm10215051 - 28 Oct 2021
Viewed by 1645
Abstract
We determined the association between CD14++CD16+ monocytes and subclinical infiltrates that do not reach the histological threshold for rejection (≥Banff IA). We studied low-immunological-risk kidney-transplant recipients in a clinical trial (NCT02284464; EudraCT 2012-003298-24) whose protocol biopsy in the third month showed no significant [...] Read more.
We determined the association between CD14++CD16+ monocytes and subclinical infiltrates that do not reach the histological threshold for rejection (≥Banff IA). We studied low-immunological-risk kidney-transplant recipients in a clinical trial (NCT02284464; EudraCT 2012-003298-24) whose protocol biopsy in the third month showed no significant changes or borderline lesions (BL). Flow cytometry was used to analyze the percentage of CD14++CD16+ monocytes in peripheral blood (PB) and blood from a fine-needle-aspiration biopsy (FNAB). A protocol biopsy was performed in 81 low-immunological-risk patients, of whom 15 were excluded (BK polyomavirus and rejection). The 28 (42.4%) with borderline lesions had significantly low levels of CD14++CD16+ in PB compared to patients with normal biopsies (7.9 ± 5.4 vs. 13.0 ± 12.8; p = 0.047). Patients without significant changes had similar percentages of CD14++CD16+ monocytes in the graft blood (GB) and FNAB blood. The percentage of these monocytes in the patients with an interstitial infiltrate, however, increased significantly in the FNAB blood compared to the GB: 16.9 ± 16.6 vs. 7.9 ± 5.4; p = 0.006. A difference of 50% in CD14++CD16+ in the GB versus the PB was a significant risk factor (p = 0.002) for BL, increasing the risk seven times. A decrease in CD14++CD16+ in the PB could be associated with the recruitment of these cells to the graft tissue in cases of subclinical BL inflammatory infiltrates below the threshold for rejection. Full article
(This article belongs to the Special Issue The Immunology and Clinical Outcome of Renal Transplantation)
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17 pages, 1390 KiB  
Article
MicroRNA Expression Changes in Kidney Transplant: Diagnostic Efficacy of miR-150-5p as Potential Rejection Biomarker, Pilot Study
by Rafael Alfaro, Isabel Legaz, Victor Jimenez-Coll, Jaouad El kaaoui El band, Helios Martínez-Banaclocha, José Antonio Galián, Antonio Parrado, Anna Mrowiec, Carmen Botella, María Rosa Moya-Quiles, Francisco Boix, Jesús de la Peña-Moral, Alfredo Minguela, Santiago Llorente and Manuel Muro
J. Clin. Med. 2021, 10(13), 2748; https://doi.org/10.3390/jcm10132748 - 22 Jun 2021
Cited by 14 | Viewed by 2941
Abstract
Background: The kidney allograft biopsy is considered the gold standard for rejection diagnosis but is invasive and could be indeterminate. Several publications point to the role of miRNA expression in suggesting its involvement in the acceptance or rejection of organ transplantation. This study [...] Read more.
Background: The kidney allograft biopsy is considered the gold standard for rejection diagnosis but is invasive and could be indeterminate. Several publications point to the role of miRNA expression in suggesting its involvement in the acceptance or rejection of organ transplantation. This study aimed to analyze microRNAs involved in the differentiation and activation of B and T lymphocytes from kidney transplant (KT) patients’ peripheral blood leukocytes to be used as biomarkers of acute renal rejection (AR). Methods: A total of 15 KT patients with and without acute rejection (AR/NAR) were analyzed and quantified by miRNA PCR array. A total of 84 miRNAs related to lymphocyte differentiation and activation B and T were studied. The functions and biological pathways were analyzed to predict the potential targets of differential expressed miRNAs. Results: Six miRNA were increased in the AR group (miR-191-5p, miR-223-3p, miR-346, miR-423-5p, miR-574-3p, and miR-181d) and miR-150-5p was increased in the NAR group. In silico studies showed a total of 2603 target genes for the increased miRNAs in AR, while for the decrease miRNA, a total of 1107 target-potential genes were found. Conclusions: Our results show that KT with AR shows a decrease in miR-150-5p expression compared to NAR, suggesting that the decrease in miR-150-5p could be related to an increased MBD6 whose deregulation could have clinical consequences. Full article
(This article belongs to the Special Issue The Immunology and Clinical Outcome of Renal Transplantation)
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18 pages, 1037 KiB  
Article
Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients
by Domingo Hernández, Juana Alonso-Titos, Teresa Vázquez, Myriam León, Abelardo Caballero, María Angeles Cobo, Eugenia Sola, Verónica López, Pedro Ruiz-Esteban, Josep María Cruzado, Joana Sellarés, Francesc Moreso, Anna Manonelles, Alberto Torío, Mercedes Cabello, Juan Delgado-Burgos, Cristina Casas, Elena Gutiérrez, Cristina Jironda, Julia Kanter, Daniel Serón and Armando Torresadd Show full author list remove Hide full author list
J. Clin. Med. 2021, 10(9), 2005; https://doi.org/10.3390/jcm10092005 - 7 May 2021
Cited by 6 | Viewed by 2283
Abstract
The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after [...] Read more.
The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients. Full article
(This article belongs to the Special Issue The Immunology and Clinical Outcome of Renal Transplantation)
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10 pages, 705 KiB  
Article
Impact of HLA Mismatching on Early Subclinical Inflammation in Low-Immunological-Risk Kidney Transplant Recipients
by Domingo Hernández, Teresa Vázquez, Juana Alonso-Titos, Myriam León, Abelardo Caballero, María Angeles Cobo, Eugenia Sola, Verónica López, Pedro Ruiz-Esteban, Josep María Cruzado, Joana Sellarés, Francesc Moreso, Anna Manonelles, Alberto Torio, Mercedes Cabello, Juan Delgado-Burgos, Cristina Casas, Elena Gutiérrez, Cristina Jironda, Julia Kanter, Daniel Serón and Armando Torresadd Show full author list remove Hide full author list
J. Clin. Med. 2021, 10(9), 1934; https://doi.org/10.3390/jcm10091934 - 29 Apr 2021
Cited by 9 | Viewed by 2375
Abstract
The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial [...] Read more.
The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06–1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04–2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions. Full article
(This article belongs to the Special Issue The Immunology and Clinical Outcome of Renal Transplantation)
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