Browsing by Subject "Kidney transplant"

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    Computational prediction of biomarkers, pathways, and new target drugs in the pathogenesis of immune-based diseases regarding kidney transplantation rejection
    (Frontiers Media, 2021-12-15) Alfaro, Rafael; Martínez Banaclocha, Helios; Llorente, Santiago; Jiménez Coll, Víctor; Galián, José Antonio; Botella, Carmen; Moya Quiles, María Rosa; Parrado, Antonio; Muro Pérez, Manuel; Minguela, Alfredo; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
    Background: The diagnosis of graft rejection in kidney transplantation (KT) patients is made by evaluating the histological characteristics of biopsy samples. The evolution of omics sciences and bioinformatics techniques has contributed to the advancement in searching and predicting biomarkers, pathways, and new target drugs that allow a more precise and less invasive diagnosis. The aim was to search for differentially expressed genes (DEGs) in patients with/without antibody-mediated rejection (AMR) and find essential cells involved in AMR, new target drugs, protein-protein interactions (PPI), and know their functional and biological analysis. Material and Methods: Four GEO databases of kidney biopsies of kidney transplantation with/without AMR were analyzed. The infiltrating leukocyte populations in the graft, new target drugs, protein-protein interactions (PPI), functional and biological analysis were studied by different bioinformatics tools. Results: Our results show DEGs and the infiltrating leukocyte populations in the graft. There is an increase in the expression of genes related to different stages of the activation of the immune system, antigenic presentation such as antibody-mediated cytotoxicity, or leukocyte migration during AMR. The importance of the IRF/STAT1 pathways of response to IFN in controlling the expression of genes related to humoral rejection. The genes of this biological pathway were postulated as potential therapeutic targets and biomarkers of AMR. These biological processes correlated showed the infiltration of NK cells and monocytes towards the allograft. Besides the increase in dendritic cell maturation, it plays a central role in mediating the damage suffered by the graft during AMR. Computational approaches to the search for new therapeutic uses of approved target drugs also showed that imatinib might theoretically be helpful in KT for the prevention and/or treatment of AMR. Conclusion: Our results suggest the importance of the IRF/STAT1 pathways in humoral kidney rejection. NK cells and monocytes in graft damage have an essential role during rejection, and imatinib improves KT outcomes. Our results will have to be validated for the potential use of overexpressed genes as rejection biomarkers that can be used as diagnostic and prognostic markers and as therapeutic targets to avoid graft rejection in patients undergoing kidney transplantation.
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    Early cytomegalovirus reactivation in renal recipients is associated with high levels of b cell maturation antigen transcript expression prior to transplantation
    (MDPI, 2023-06-22) Alfaro, Rafael; Rodríguez Aguilar, Luis; Llorente, Santiago; Jiménez Coll, Víctor; Martínez Banaclocha, Helios; Galián, José Antonio; Botella, Carmen; Moya Quiles, María Rosa; Muro Pérez, Manuel; Minguela, Alfredo; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
    Cytomegalovirus (CMV) infection is the most frequent infection episode in kidney transplant (KT) recipients. Reactivation usually occurs in the first three months after transplantation and is associated with higher cellular and/or antibody-mediated rejection rates and poorer graft performance. CMV induces the expression of BAFF (B-cell-activating factor, a cytokine involved in the homeostasis of B cells), which communicates signals for survival and growth to B cells and virus-specific plasma cells via the R-BAFF (BAFF receptor), TACI (the calcium modulator, the cyclophilin ligand interactor), and BCMA (B cell maturation antigen) receptors. These molecules of the BAFF system have also been suggested as biomarkers for the development of alloantibodies and graft dysfunction. This prospective study included 30 CMV-IgG seropositive KT recipients. The expression levels of the genes BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA) in peripheral blood leukocytes (PBL) pre-KT were determined using qPCR. qPCR was also used to monitor CMV reactivation in the first three months following KT. The remainder of the KT recipients were classified as CMV− reactivation, and those with more than 500 copies/mL in at least one sample were classified as CMV+ reactivation. There were no discernible variations in the BAFF-R and TACI transcript expression levels. In the CMV+ group, we examined the relationship between the transcript levels and peak viremia. Peak viremia levels and BCMA transcript levels showed a strong correlation. BAFF-R and TACI expressions showed no measurable differences. In patients with early CMV reactivation, high BCMA receptor expression was associated with increased plasmablast, lymphocyte B cell class-switched levels (LBCS), and viral load. Our findings demonstrate that pre-KT BCMA transcript levels increased in KT recipients with early CMV reactivation. These transcript levels positively correlate with peak viremia and weakly with plasmablast and LBCS levels in PBLs.
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    Evaluating the link between BAFF system gene expression and acute rejection development in kidney transplantation
    (MDPI, 2022-07-07) Alfaro, Rafael; Llorente, Santiago; Jiménez Coll, Víctor; Martínez Banaclocha, Helios; Galián, José Antonio; Botella, Carmen; Moya Quiles, María Rosa; Muro Pérez, Manuel; Peña Moral, Jesús de la; Minguela, Alfredo; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
    B-cell activating factor (BAFF) system signaling is critical for B-cell homeostasis, effector functions, and tolerance maintenance in transplants, but it has not been studied in kidney transplant recipients (KTRs). The aim was to analyze the changes in BAFF system expression in KTRs with/without acute rejection (AR/NAR). The BAFF system expression was analyzed by qPCR in 40 KTRs. A meta-analysis of BAFF system expression and histological renal damage was identified by the Chronic Allograft Damage Index (CADI) and performed from the GEO database. Proliferation-inducing ligand (APRIL) expression increased at three- and six-months post-KT (p = 0.014 and p < 0.001). B-cell maturation antigen (BCMA) expression increased at six-months post-KT (p = 0.038). BAFF expression remained stable in NAR-KTRs, but was increased in CADI concerning the No-CADI group at one year (p = 0.008). BCMA expression increased in the CADI group at one- (p = 0.001) and six-years post-KT (p = 0.024). At three months, the transmembrane activator and calcium modulator interactor (TACI) gene significantly elevated KTRs with DSAs (donor-specific antibody; p = 0.034). KTRs with DSAs significantly increase the B-cell activating factor receptor (R-BAFF; p = 0.021) and TACI (p = 0.018) between pre- and three-month post-KT. Changes in the expression of the BAFF system increase during post-KTR in the development of AR and chronic allograft damage, and could be an important pathological tool to detect and prevent kidney graft outcomes.
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    Evaluation of antibodies directed against two GPCRs, Anti-AT1R and Anti-ETAR, on kidney transplant outcome
    (Bentham Science Publishers, 2021-07-06) El kaaoui El band, Jaouad; Llorente, Santiago; Martínez García, Pedro; Jiménez Coll, Víctor; Boix, Francisco; Galián, Jose Antonio; Martínez Banaclocha, Helios; Botella, Carmen; Moya Quiles, María Rosa; Minguela, Alfredo; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
    Background: The role of an alloimmune response against non-self-antigens is established in organ transplantation. HLA incompatibilities are mainly responsible for this recognition between donor and recipient, but they may also be involved in the reactivity against other alloantigens expressed on the allograft resulting from an autoimmune response developed against selfantigens. Objective: Our study aimed to determine the presence of non-anti-HLA antibodies (anti-AT1R and anti-ETAR) in sera from patients with end-stage renal disease, who underwent kidney transplantation in pre- and post-transplantation samples to study their influence on the development and evolution of acute humoral rejections and DSAs. Methods: Antibodies (Abs) against two G protein-coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR), have been detected in the sera of transplant recipients, who experience allograft dysfunction, patients with coronary heart disease, marginal hypertension and refractory, vascular lesions, myocardial hypertrophy and chronic inflammatory diseases, such as atherosclerosis or sclerosis. Results: Kidney graft recipients were monitored for anti-ETAR, -AT1R, and -HLA Abs in pre-and post-transplant evolution, and anti-AT1R and/or -ETAR Abs were detected in 24% of recipients (22.4% with anti-AT1R Abs and 9.8% with anti-ETAR Abs). Due to acute humoral rejection, Graft loss was detected in 6.4% of patients with anti-GPCRs non-HLA Abs, and 3.2% had DSA anti-HLA Abs. In this research, we have described how the function of the anti-GPCRs autoAbs and how these Abs that activate GPCRs could influence graft outcome. Conclusion: In conclusion, there is a high association of non-HLA anti-GPCRs Abs levels with reduced kidney function after transplantation, especially in the presence of DSA anti-HLA Abs. Although more studies are needed, anti-AT1R and anti-ETAR antibodies may be helpful biomarkers that allow the risk of graft loss to be assessed.
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    Evaluation of desensitizing therapies for donor-specific antibodies in confirmed humoral allograft rejection in kidney transplantation: experience of a center for 10 years
    (Elsevier, 2026-02-13) Martínez-Alcaraz, Marta; Gil, Mercedes; Llorente, Santiago; Botella, Carmen; Galián, José Antonio; González-López, Rosana; Fernández-González, Marina; Alegría, María José; Hita, Alicia; Moya, María Rosa; Martinez-Banaclocha, Helios; Muro-Pérez, Manuel; Muro, Javier; Minguela, Alfredo; Legaz Pérez, Isabel; Muro, Manuel; Ciencias Sociosanitarias; Facultad de Química
    Donor-specific antibodies (DSAs) in the recipient's serum are directed against donor-mismatched Human Leukocyte Antigen (HLA) antigens found on graft endothelial cells. These DSAs may be responsible for antibody-mediated rejection (AMR) in patients undergoing kidney transplantation. Once they are developed in the post-transplant period, a desensitizing treatment must be instituted to reduce these DSAs and not cause damage to the graft. The objectives were to analyze our cases of confirmed AMR in a series of kidney recipients over 10 years and to assess the impact of the anti-rejection treatments (ART) on DSAs in these patients. Methods: This study evaluated the presence of DSAs in the sera of 33 patients, identified through Luminex, who developed DSAs associated with renal graft deterioration. Assessments were conducted at the time of the event and/or biopsy, with DSA levels ≥1500 mean fluorescence intensity (MFI) units considered positive. ART included plasma exchange, Intravenous Immunoglobulin (IVIG), boluses of methylprednisolone, anti-CD20, anti-IL-6R, or increased doses of immunosuppressants. Results: It was observed that ART with Tocilizumab shows the most decrease in MFI of DSAs over time (p < 0.05); this decrease occurs in most patients treated with progressive recovery of renal function. However, when we analyze the post-transplant ART in those patients with plasma exchange (PE), IVIG, and Rituximab, slightly heterogeneous data are observed, although some patients had a slight decrease in MFI of DSAs after treatment, the effect was not as apparent as with Tocilizumab. The results were also heterogeneous regarding the increase in immunosuppression, although there was a greater tendency to decrease the MFI of DSAs. HLA class I DSAs respond better to desensitizing treatment with PE/IVIG, while HLA class II DSAs, especially anti-DQ antibodies, show a more variable evolution. Conclusions: The use of Tocilizumab in chronic AMR produced the greatest decrease in the MFI of the DSAs and the recovery of the renal function of the graft compared to other ARTs. Treatment with PP/IA/IVIG/ Rituximab also showed greater variability in the face of a decrease in DSA, depending on the type of patient. Finally, increased immunosuppression as an ART also showed great variability, although with a greater tendency to decrease DSA. Our results should be evaluated with caution for our small number that could not draw definitive conclusions.
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    Influence and role of regulatory B cells in organ transplantation: the state of the art, prospects, and emerging insights
    (MDPI, 2025-11-07) Fernández-González, Marina; Llorente, Santiago; Galián, José Antonio; Botella, Carmen; González-López, Rosana; Alegría, María José; Hita, Alicia; Moya-Quiles, María Rosa; Martinez-Banaclocha, Helios; Muro-Pérez, Manuel; Muro, Javier; Minguela, Alfredo; Legaz Pérez, Isabel; Muro, Manuel; Ciencias Sociosanitarias; Facultad de Química
    B cells have attracted increasing interest in the field of organ transplantation due to their newly discovered immunoregulatory properties in alloimmune responses. Traditionally, B cells have been primarily associated with adaptive immunity to foreign substances and alloreactive immune response to allografts, differentiating into antibody-producing plasma cells or memory cells upon antigen recognition and T cell collaboration. However, the existence of B cells with regulatory functions (Bregs) in humans has been widely confirmed, highlighting the presence of this subset, which has immunosuppressive properties and which might contribute to allograft tolerance, within the B cell compartment in humans and mice. In this mini review, we summarize all the information available in the published reports about the role of regulatory B cells in solid organ transplantation.
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    MicroRNA expression changes in kidney transplant: diagnostic efficacy of miR-150-5p as potential rejection biomarker, pilot study
    (MDPI, 2021-06-22) Alfaro, Rafael; Jiménez Coll, Víctor; El kaaoui El band, Jaouad; Martínez Banaclocha, Helios; Galián, José Antonio; Parrado, Antonio; Mrowiec, Anna; Botella, Carmen; Moya Quiles, María Rosa; Boix, Francisco; Peña Moral, Jesús de la; Minguela, Alfredo; Llorente, Santiago; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
    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.
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    Monitoring of B cell in kidney transplantation: development of a novel clusters analysis and role of transitional B cells in transplant outcome
    (MDPI, 2021-04-01) Alfaro, Rafael; González Martínez, Gema; Jiménez Coll, Víctor; Martínez Banaclocha, Helios; Galián, José Antonio; Botella, Carmen; Peña Moral, Jesús de la; Moya Quiles, María Rosa; Campillo, José Antonio; Minguela, Alfredo; Llorente, Santiago; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
    Background: B lymphocytes (BL) seem to play an important role in transplantation, although the and role of different subpopulations in monitoring and outcome is not clear. Our aim was to monitoring immunological profiles based on BL subpopulations in kidney recipients (KR) with the risk of acute rejection (AR). Methods: Monitoring of BL subpopulations was performed by flow cytometry in PBLs before transplantation and three and six months after transplantation (PTX). We used two methodological approaches, a traditional analysis, and a novel cluster analysis, to determine the association between BL subpopulations, AR incidence, and graft function. Results: After three months of PTX, KRs with a B phenotype enriched in transitional BL and plasmablasts had better kidney function and lower AR incidence. KRs with decreased transitional BL and plasmablasts were associated with lower kidney function and higher AR PTX. KRs that had an increase in transitional BL PTX had a better clinical outcome. The increase in transitory BL during PTX was also associated with an increase in Tregs. Indeed, KRs receiving thymoglobulin as induction therapy showed a slight decrease in the relative frequency of naive BLs after three months of PTX. Conclusion: The monitoring of BL subpopulations may serve as a non-invasive tool to improve immunological follow-up of patients after kidney transplantation. However, further studies are needed to confirm the obtained results, define cut-off values, and standardize more optimal and even custom/customized protocols.
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    Monitoring of soluble forms of BAFF System (BAFF, APRIL, sR-BAFF, sTACI and sBCMA) in kidney transplantation
    (Springer, 2022-09-22) Alfaro, Rafael; Llorente, Santiago; Martínez, Pedro; Jiménez Coll, Víctor; Martínez Banaclocha, Helios; Galián, José Antonio; Botella, Carmen; Moya Quiles, María Rosa; Peña Moral, Jesús de la; Minguela, Alfredo; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
    BAFF system plays an essential role in B cells homeostasis and tolerance, although it has widely not been tested in transplantation with doubtful results. The main purpose was to study the BAFF soluble forms and their correlation with acute rejection (AR) and donor-specific antibodies production. Serum levels of BAFF, APRIL, and soluble forms of their receptors were analyzed in renal recipients with and without acute rejection (AR/NAR) appearance. All molecules were evaluated at pre- and post-transplantation. sTACI showed a significant correlation with BAFF and sR-BAFF levels, and sBCMA also showed a positive correlation with sAPRIL levels. A significant increase in sAPRIL levels in patients suffering AR was also found, and ROC curves analysis showed an AUC = 0.724, a concentration of 6.05 ng/ml (sensitivity: 66.7%; specificity: 73.3%), the best cutoff point for predicting AR. In the post-transplant dynamics of sAPRIL levels in the longitudinal cohort, we observed a significant decrease at 3 and 6 month post-transplantation compared to pretransplantation status. We also observed that recipients with high pre-transplant levels of sAPRIL generated antibodies earlier than those with lower sAPRIL levels, although their long-term post-transplantation was not different. Our results show that elevated serum levels of APRIL may be helpful as a biomarker for the diagnosis of AR, although the longitudinal study shows that it is not helpful as a prognostic biomarker.
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    Trasplante Renal: formación quirúrgica durante la residencia de urología en el Hospital de Clínicas, Montevideo, Uruguay
    (Universidad de Murcia. Servicio de publicaciones, 2023) Choca Firpo, María Eugenia; Montaña, Emmanuel; Martínez, Levin; Vilche, Sofía
    Objetivo: Describir la actividad quirúrgica correspondiente a la cirugía del receptor deun residente de urología durante la rotación de trasplante renal en el Hospital de Clínicas,Montevideo Uruguay, en el período abril 2023 a julio 2023.Materiales y métodos: Se realizó un estudio descriptivo. Las principales variables de interés sonnúmero de cirugías realizadas, tipo de reimplante ureteral y tiempo operatorio. Los datos fueronrecabados del registro realizado en el programa de descripciones operatorias de la institución yanalizados en Excel versión 2019. Resultados: En un período de cuatro meses, el residente realizóun total de 16 cirugías de receptor. Se realizaron sólo mediante dos técnicas quirúrgicas dereimplante ureteral; Lich-Gregoir y Taguchi. En la totalidad de las intervenciones el residente tuvoel rol de cirujano. En un 25% (n=4) de las intervenciones se realizó la técnica Lich-Gregoir y en un75% (n=12) la técnica Taguchi. La media del tiempo operatorio fue de 95.12 minutos con un desvíoestándar de 23.42 minutos en general. Conclusión: La rotación por trasplante renal durante la formación del residente de urología en Uruguay le permite adquirir destrezas quirúrgicas, no sólo aplicables en la cirugía de trasplante renal. Durante la rotación por trasplante renal, el residente de urología en Uruguay alcanza a realizar el 10% de los implantes ureterales sugerido por la Asociación Española de Urología (AEU) para su formación. El manejo multidisciplinario de los pacientes en conjunto a cirugía vascular y nefrología es fundamental en la formación del residente