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2. Delayed Graft Function After Kidney Transplantation: The Role of Residual Diuresis and Waste Products, as Oxalic Acid and Its Precursors.

Author

Hospers, Gideon Post, Visser, Wesley J., Verhoeven, Jeroen G. H. P., Laging, Mirjam, Baart, Sara J., Mertens zur Borg, Ingrid R. A. M., Hesselink, Dennis A., de Mik-van Egmond, Anneke M. E., Betjes, Michiel G. H., van Agteren, Madelon, Severs, David, van de Wetering, Jacqueline, Zietse, Robert, Vos, Michel J., Kema, Ido P., Kho, Marcia M. L., Reinders, Marlies E. J., and Roodnat, Joke I.

Subjects
OXALIC acid, WASTE products, KIDNEY physiology, LOGISTIC regression analysis, GLYCOLIC acid
Abstract

Delayed graft function (DGF) after kidney transplantation heralds a worse prognosis. In patients with hyperoxaluria, the incidence of DGF is high. Oxalic acid is a waste product that accumulates when kidney function decreases. We hypothesize that residual diuresis and accumulated waste products influence the DGF incidence. Patients transplanted between 2018-2022 participated in the prospective cohort study. Pre-transplant concentrations of oxalic acid and its precursors were determined. Data on residual diuresis and other recipient, donor or transplant related variables were collected. 496 patients were included, 154 were not on dialysis. Oxalic acid, and glyoxylic acid, were above upper normal concentrations in 98.8%, and 100% of patients. Residual diuresis was ≤150 mL/min in 24% of patients. DGF occurred in 157 patients. Multivariable binary logistic regression analysis demonstrated a significant influence of dialysis type, recipient BMI, donor type, age, and serum creatinine on the DGF risk. Residual diuresis and glycolic acid concentration were inversely proportionally related to this risk, glyoxylic acid directly proportionally. Results in the dialysis population showed the same results, but glyoxylic acid lacked significance. In conclusion, low residual diuresis is associated with increased DGF incidence. Possibly accumulated waste products also play a role. Pre-emptive transplantation may decrease the incidence of DGF. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Determination of the clinical relevance of donor epitope‐specific HLA‐antibodies in kidney transplantation

Author

Kardol‐Hoefnagel, Tineke, primary, Senejohnny, Danial Mohammadi, additional, Kamburova, Elena G., additional, Wisse, Bram W., additional, Reteig, Leon, additional, Gruijters, Maartje L., additional, Joosten, Irma, additional, Allebes, Wil A., additional, van der Meer, Arnold, additional, Hilbrands, Luuk B., additional, Baas, Marije C., additional, Spierings, Eric, additional, Hack, Cornelis E., additional, van Reekum, Franka E., additional, van Zuilen, Arjan D., additional, Verhaar, Marianne C., additional, Bots, Michiel L., additional, Drop, Adriaan C. A. D., additional, Plaisier, Loes, additional, Melchers, Rowena C. A., additional, Seelen, Marc A. J., additional, Sanders, Jan Stephan, additional, Hepkema, Bouke G., additional, Lambeck, Annechien J. A., additional, Bungener, Laura B., additional, Roozendaal, Caroline, additional, Tilanus, Marcel G. J., additional, Voorter, Christina E., additional, Wieten, Lotte, additional, van Duijnhoven, Elly M., additional, Gelens, Mariëlle A. C. J., additional, Christiaans, Maarten H. L., additional, van Ittersum, Frans J., additional, Nurmohamed, Shaikh A., additional, Lardy, Neubury M., additional, Swelsen, Wendy, additional, van der Pant, Karlijn A. M. I., additional, van der Weerd, Neelke C., additional, ten Berge, Ineke J. M., additional, Hoitsma, Andries, additional, van der Boog, Paul J. M., additional, de Fijter, Johan W., additional, Betjes, Michiel G. H., additional, Roelen, Dave L., additional, Claas, Frans H., additional, Bemelman, Frederike J., additional, Senev, Aleksandar, additional, Naesens, Maarten, additional, Heidt, Sebastiaan, additional, and Otten, Henny G., additional

Published
2024
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9. Increasing Kidney-Exchange Options Within the Existing Living Donor Pool With CIAT: A Pilot Implementation Study

Author

de Klerk, Marry, primary, Kal-van Gestel, Judith A., additional, Roelen, Dave, additional, Betjes, Michiel G. H., additional, de Weerd, Annelies E., additional, Reinders, Marlies E. J., additional, van de Wetering, Jacqueline, additional, Kho, Marcia M. L., additional, Glorie, Kristiaan, additional, and Roodnat, Joke I., additional

Published
2023
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12. The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients.

Author

Betjes, Michiel G. H., Gestel, Judith Kal-van, Roodnat, Joke I., and de Weerd, Annelies E.

Subjects
*GRAFT rejection, *KIDNEY transplantation, *AGE groups, *MIDDLE age, *BK virus, *OLDER people
Abstract

It is not known whether antibody-mediated rejection (ABMR) is age-related, whether it plateaus late after transplantation, and to what extent it contributes to graft loss in older recipients. Patients transplanted between 2010 and 2015 (n = 1,054) in a single center had regular follow-up until January 2023. Recipients were divided into age groups at transplantation: 18-39 years ("young"), 40-55 years ("middle age"), and >55 years ("elderly"). Ten years after transplantation the cumulative % of recipients with ABMR was 17% in young, 15% in middle age, and 12% in elderly recipients (p < 0.001). The cumulative incidence of ABMR increased over time and plateaued 8-10 years after transplantation. In the elderly, with a median follow-up of 7.5 years, on average 30% of the recipients with ABMR died with a functional graft and ABMR contributed only 4% to overall graft loss in this group. These results were cross-validated in a cohort of recipients with >15 years follow-up. Multivariate cox-regression analysis showed that increasing recipient age was independently associated with decreasing risk for ABMR. In conclusion, the cumulative risk for ABMR is age-dependent, plateaus late after transplantation, and contributes little to overall graft loss in older recipients. [ABSTRACT FROM AUTHOR]

Published
2024
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13. The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

Author

Betjes, Michiel G. H., Kal-van Gestel, Judith, Roodnat, Joke I., de Weerd, Annelies E., Betjes, Michiel G. H., Kal-van Gestel, Judith, Roodnat, Joke I., and de Weerd, Annelies E.

Abstract

It is not known whether antibody-mediated rejection (ABMR) is age-related, whether it plateaus late after transplantation, and to what extent it contributes to graft loss in older recipients. Patients transplanted between 2010 and 2015 (n = 1,054) in a single center had regular follow-up until January 2023. Recipients were divided into age groups at transplantation: 18-39 years ("young"), 40-55 years ("middle age"), and >55 years ("elderly"). Ten years after transplantation the cumulative % of recipients with ABMR was 17% in young, 15% in middle age, and 12% in elderly recipients (p < 0.001). The cumulative incidence of ABMR increased over time and plateaued 8-10 years after transplantation. In the elderly, with a median follow-up of 7.5 years, on average 30% of the recipients with ABMR died with a functional graft and ABMR contributed only 4% to overall graft loss in this group. These results were cross-validated in a cohort of recipients with >15 years follow-up. Multivariate cox-regression analysis showed that increasing recipient age was independently associated with decreasing risk for ABMR. In conclusion, the cumulative risk for ABMR is age-dependent, plateaus late after transplantation, and contributes little to overall graft loss in older recipients.

Published
2023

14. Unilateral renal atrophy 4 years after renal sympathetic denervation:a case report

Author

Zeijen, Victor J M, Hirsch, Alexander, Betjes, Michiel G H, Daemen, Joost, Zeijen, Victor J M, Hirsch, Alexander, Betjes, Michiel G H, and Daemen, Joost

Abstract

Renal sympathetic denervation (RDN) carries a low risk of renal artery stenosis, and most cases occur within the first year. However, limited data are available on long-term incidence. Here, we present a case of a 68-year-old woman who underwent radiofrequency RDN for resistant hypertension. Ambulatory blood pressure improved following RDN and uptitration of antihypertensive drugs. Between year 3 and 4 after RDN, eGFR reduced from 87 to 50 ml/min per 1.73 m2. Ultrasound imaging revealed left renal atrophy, while subsequent magnetic resonance angiography showed a haemodynamically significant stenosis of the left renal artery. The patient remained in good clinical condition with stable blood pressure, while eGFR mildly deteriorated during a 6-year follow-up period. This case of renal artery stenosis occurred in a patient with multiple risk factors. A causal relationship to the RDN procedure cannot be confirmed nor ruled out. Long-term surveillance for adverse events should be considered in all RDN patients.

Published
2023

17. Polyfunctional donor-reactive T cells are associated with acute T-cell-mediated rejection of the kidney transplant.

Author

Litjens, Nicolle H R, van der List, Amy C J, Klepper, Mariska, Prevoo, Fréderique, Boer, Karin, Hesselink, Dennis A, and Betjes, Michiel G H

Subjects
T cells, KIDNEY transplantation, CD28 antigen, CD8 antigen, CD4 antigen
Abstract

Acute T-cell-mediated rejection (aTCMR) still remains a clinical problem after kidney transplantation despite significant improvements in immunosuppressive regimens. Polyfunctional T cells, i.e. T cells producing multiple pro-inflammatory cytokines, are believed to be the most relevant T cells in an immune response. The aim of this study was to determine whether polyfunctional donor-reactive T cells are associated with aTCMR. In a case–control study, 49 kidney transplant recipients with a biopsy-proven aTCMR in the first year after transplantation were included, as well as 51 controls without aTCMR. Circulating donor-reactive T cells were identified by the expression of CD137 after short-term co-culture with donor antigen-presenting cells. Polyfunctional donor-reactive T cells were further characterized by dissection into different T-cell subsets encompassing the spectrum of naïve to terminally differentiated effector T cells. Prior to kidney transplantation, proportions of donor-reactive CD4+ (0.03% versus 0.02%; P < 0.01) and CD8+ (0.18% versus 0.10%; P < 0.01) CD137++ T cells were significantly higher in recipients with a biopsy-proven aTCMR versus non-rejectors. Polyfunctionality was higher (P = 0.03) in this subset of CD137-expressing T cells. These cells were predominantly of the EM/EMRA-phenotype, with polyfunctional donor-reactive CD137++CD4+ T cells predominantly co-expressing CD28 whereas approximately half of the polyfunctional CD137++CD8+ T cells co-expressed CD28. In addition, at the time of aTCMR, polyfunctional donor-reactive CD137++ CD4+, but not CD8+, T cells, were specifically decreased by 75% compared to before transplantation in recipients with as well as those without an aTCMR. Prior to transplantation, the proportion of polyfunctional donor-reactive CD137++ T cells is associated with the occurrence of a biopsy-proven aTCMR within the first year after transplantation. Acute TCMR remains a clinical problem after kidney transplantation despite significant improvements in immunosuppressive regimens. Poly-functional (producing ≥2 cytokines) T cells are believed to be the most relevant T cells in an immune response. Prior to kidney transplantation proportions of poly-functional CD137 high expressing donor-reactive CD4+ and CD8+ T cells are higher in recipients experiencing an acute TCMR within the first year after transplantation compared to those who remained free of rejection. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Combined Analysis of Transcriptome and T-Cell Receptor Alpha and Beta (TRA /TRB ) Repertoire in Paucicellular Samples at the Single-Cell Level

Author

Litjens, Nicolle H R, Langerak, Anton W, Azmani, Zakia, den Dekker, Xander, Betjes, Michiel G H, Brouwer, Rutger W W, van IJcken, Wilfred F J, Internal Medicine, Immunology, and Cell biology

Subjects
Receptors, Antigen, T-Cell, alpha-beta, Receptors, Antigen, T-Cell, High-Throughput Nucleotide Sequencing, Immunoglobulins, Transcriptome, Research Article
Abstract

With the advent of next-generation sequencing (NGS) methodologies, the total repertoires of B and T cells can be disclosed in much more detail than ever before. Even though many of these strategies do provide in-depth and high-resolution information of the immunoglobulin (IG) and/or T-cell receptor (TR) repertoire, one clear disadvantage is that the IG/TR profiles cannot be connected to individual cells. Single-cell technologies do allow to study the IG/TR repertoire at the individual cell level. This is especially relevant in cell samples in which much heterogeneity of the cell population is expected. By combining the IG/TR repertoire with transcriptome data, the reactivity of the B or T cell can be associated with activation or maturation stages. An additional advantage of such single-cell technologies is that the combination of both IG and both TR chains can be studied on a per cell basis, which better reflects the antigen receptor reactivity of cells. Here we present the ICELL8 single-cell method for the parallel analysis of the TR repertoire and transcriptome, which is especially useful in samples that contain relatively few cells.

Published
2022

28. Current Tolerance-Associated Peripheral Blood Gene Expression Profiles After Liver Transplantation Are Influenced by Immunosuppressive Drugs and Prior Cytomegalovirus Infection

Author

Duizendstra, Aafke A., primary, van der Grift, Michelle V., additional, Boor, Patrick P., additional, Noordam, Lisanne, additional, de Knegt, Robert J., additional, Peppelenbosch, Maikel P., additional, Betjes, Michiel G. H., additional, Litjens, Nicolle H. R., additional, and Kwekkeboom, Jaap, additional

Published
2022
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29. T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

Author

Peereboom, Emma T. M., primary, Matern, Benedict M., additional, Tomosugi, Toshihide, additional, Niemann, Matthias, additional, Drylewicz, Julia, additional, Joosten, Irma, additional, Allebes, Wil A., additional, van der Meer, Arnold, additional, Hilbrands, Luuk B., additional, Baas, Marije C., additional, van Reekum, Franka E., additional, Verhaar, Marianne C., additional, Kamburova, Elena G., additional, Seelen, Marc A. J., additional, Sanders, Jan Stephan, additional, Hepkema, Bouke G., additional, Lambeck, Annechien J., additional, Bungener, Laura B., additional, Roozendaal, Caroline, additional, Tilanus, Marcel G. J., additional, Voorter, Christien E., additional, Wieten, Lotte, additional, van Duijnhoven, Elly M., additional, Gelens, Mariëlle A. C. J., additional, Christiaans, Maarten H. L., additional, van Ittersum, Frans J., additional, Nurmohamed, Azam, additional, Lardy, Neubury M., additional, Swelsen, Wendy, additional, van der Pant, Karlijn A., additional, van der Weerd, Neelke C., additional, ten Berge, Ineke J. M., additional, Bemelman, Fréderike J., additional, de Vries, Aiko P. J., additional, de Fijter, Johan W., additional, Betjes, Michiel G. H., additional, Roelen, Dave L., additional, Claas, Frans H., additional, Otten, Henny G., additional, Heidt, Sebastiaan, additional, van Zuilen, Arjan D., additional, Kobayashi, Takaaki, additional, Geneugelijk, Kirsten, additional, and Spierings, Eric, additional

Published
2021
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30. ABO‐incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity‐matched analysis

Author

Weerd, Annelies E., primary, Brand, Jan A. J. G., additional, Bouwsma, Hanneke, additional, Vries, Aiko P. J., additional, Dooper, Ine (Ph.) M. M., additional, Sanders, Jan‐Stephan F., additional, Christiaans, Maarten H. L., additional, Reekum, Franka E., additional, Zuilen, Arjan D., additional, Bemelman, Frederike J., additional, Nurmohamed, Azam S., additional, Agteren, Madelon, additional, Betjes, Michiel G. H., additional, Jong, Margriet F. C., additional, and Baas, Marije C., additional

Published
2021
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32. Heterogeneity of Dendritic Cells and Nomenclature

Author

Hoefsmit, Elisabeth C. M., Arkema, Joanne M. S., Betjes, Michiel G. H., Havenith, Carin E. G., van Vugt, Ellen, Beelen, Robert H. J., Kamperdijk, Eduard W. A., Kamperdijk, Eduard W. A., editor, Nieuwenhuis, Paul, editor, and Hoefsmit, Elisabeth C. M., editor

Published
1993
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36. The number of donor HLAderived T cell epitopes available for indirect antigen presentation determines the risk for vascular rejection after kidney transplantation.

Author

Betjes, Michiel G. H., Peereboom, Emma T. M., Otten, Henny G., and Spierings, Eric

Subjects
KIDNEY transplantation, ANTIGEN presentation, T cells, EPITOPES, GRAFT rejection
Abstract

The role of the indirect T-cell recognition pathway of allorecognition in acute T cell-mediated rejection (aTCMR) is not well defined. The amount of theoretical T-cell epitopes available for indirect allorecognition can be quantified for donor-recipient combinations by the Predicted Indirectly ReCognizable HLA Epitopes algorithm (PIRCHE-II). The PIRCHE-II score was calculated for 688 donor kidney-recipient combinations and associated with the incidence of first-time diagnosed cases of TCMR. A diagnosis of TCMR was made in 182 cases; 121 cases of tubulo-interstitial rejection cases (79 cases of borderline TCMR, 42 cases of TCMR IA-B) and 61 cases of vascular TCMR (TCMR II-III). The PIRCHE-II score for donor HLA-DR/DQ (PIRCHE-II DR/DQ) was highly associated with vascular rejection. At one year after transplantation, the cumulative percentage of recipients with a vascular rejection was 12.7%, 8.6% and 2.1% within respectively the high, medium and low tertile of the PIRCHE-II DR/DQ score (p<0.001). In a multivariate regression analysis this association remained significant (p<0.001 for PIRCHE-II DR/DQ tertiles). The impact of a high PIRCHE-II DR/DQ score was mitigated by older recipient age and a living donor kidney. In conclusion, indirect antigen presentation of donor HLApeptides may significantly contribute to the risk for acute vascular rejection. [ABSTRACT FROM AUTHOR]

Published
2022
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39. Activated CD4 + T Cells and Highly Differentiated Alloreactive CD4 + T Cells Distinguish Operationally Tolerant Liver Transplantation Recipients

Author

Duizendstra, Aafke A., primary, Knegt, Robert J., additional, Mancham, Shanta, additional, Klepper, Mariska, additional, Roelen, Dave L., additional, Brand‐Schaaf, Simone H., additional, Boor, Patrick P., additional, Doukas, Michail, additional, Man, Robert A., additional, Sprengers, Dave, additional, Peppelenbosch, Maikel P., additional, Betjes, Michiel G. H., additional, Kwekkeboom, Jaap, additional, and Litjens, Nicolle H. R., additional

Published
2021
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40. T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

Author

CTI Spierings, CTI Computational Immunology Core, Infection & Immunity, CTI Borghans, MS Nefrologie, Circulatory Health, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, CDL Patiëntenzorg MI, Cancer, Peereboom, Emma T M, Matern, Benedict M, Tomosugi, Toshihide, Niemann, Matthias, Drylewicz, Julia, Joosten, Irma, Allebes, Wil A, van der Meer, Arnold, Hilbrands, Luuk B, Baas, Marije C, van Reekum, Franka E, Verhaar, Marianne C, Kamburova, Elena G, Seelen, Marc A J, Sanders, Jan Stephan, Hepkema, Bouke G, Lambeck, Annechien J, Bungener, Laura B, Roozendaal, Caroline, Tilanus, Marcel G J, Voorter, Christien E, Wieten, Lotte, van Duijnhoven, Elly M, Gelens, Mariëlle A C J, Christiaans, Maarten H L, van Ittersum, Frans J, Nurmohamed, Azam, Lardy, Neubury M, Swelsen, Wendy, van der Pant, Karlijn A, van der Weerd, Neelke C, Ten Berge, Ineke J M, Bemelman, Fréderike J, de Vries, Aiko P J, de Fijter, Johan W, Betjes, Michiel G H, Roelen, Dave L, Claas, Frans H, Otten, Henny G, Heidt, Sebastiaan, van Zuilen, Arjan D, Kobayashi, Takaaki, Geneugelijk, Kirsten, Spierings, Eric, CTI Spierings, CTI Computational Immunology Core, Infection & Immunity, CTI Borghans, MS Nefrologie, Circulatory Health, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, CDL Patiëntenzorg MI, Cancer, Peereboom, Emma T M, Matern, Benedict M, Tomosugi, Toshihide, Niemann, Matthias, Drylewicz, Julia, Joosten, Irma, Allebes, Wil A, van der Meer, Arnold, Hilbrands, Luuk B, Baas, Marije C, van Reekum, Franka E, Verhaar, Marianne C, Kamburova, Elena G, Seelen, Marc A J, Sanders, Jan Stephan, Hepkema, Bouke G, Lambeck, Annechien J, Bungener, Laura B, Roozendaal, Caroline, Tilanus, Marcel G J, Voorter, Christien E, Wieten, Lotte, van Duijnhoven, Elly M, Gelens, Mariëlle A C J, Christiaans, Maarten H L, van Ittersum, Frans J, Nurmohamed, Azam, Lardy, Neubury M, Swelsen, Wendy, van der Pant, Karlijn A, van der Weerd, Neelke C, Ten Berge, Ineke J M, Bemelman, Fréderike J, de Vries, Aiko P J, de Fijter, Johan W, Betjes, Michiel G H, Roelen, Dave L, Claas, Frans H, Otten, Henny G, Heidt, Sebastiaan, van Zuilen, Arjan D, Kobayashi, Takaaki, Geneugelijk, Kirsten, and Spierings, Eric

Published
2021

41. ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis

Author

MS Nefrologie, Circulatory Health, de Weerd, Annelies E, van den Brand, Jan A J G, Bouwsma, Hanneke, de Vries, Aiko P J, Dooper, Ine Ph M M, Sanders, Jan-Stephan F, Christiaans, Maarten H L, van Reekum, Franka E, van Zuilen, Arjan D, Bemelman, Frederike J, Nurmohamed, Azam S, van Agteren, Madelon, Betjes, Michiel G H, de Jong, Margriet F C, Baas, Marije C, MS Nefrologie, Circulatory Health, de Weerd, Annelies E, van den Brand, Jan A J G, Bouwsma, Hanneke, de Vries, Aiko P J, Dooper, Ine Ph M M, Sanders, Jan-Stephan F, Christiaans, Maarten H L, van Reekum, Franka E, van Zuilen, Arjan D, Bemelman, Frederike J, Nurmohamed, Azam S, van Agteren, Madelon, Betjes, Michiel G H, de Jong, Margriet F C, and Baas, Marije C

Published
2021

49. Validation of a Combined Transcriptome and T Cell Receptor Alpha/Beta (TRA/TRB) Repertoire Assay at the Single Cell Level for Paucicellular Samples

Author

Litjens, Nicolle H. R., primary, Langerak, Anton W., additional, van der List, Amy C. J., additional, Klepper, Mariska, additional, de Bie, Maaike, additional, Azmani, Zakia, additional, den Dekker, Alexander T., additional, Brouwer, Rutger W. W., additional, Betjes, Michiel G. H., additional, and Van IJcken, Wilfred F. J., additional

Published
2020
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