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Association of intraindividual tacrolimus variability with de novo donor-specific HLA antibody development and allograft rejection in pediatric kidney transplant recipients with low immunological risk
BACKGROUND: Tacrolimus (Tac) intraindividual variability (TacIPV) in pediatric kidney transplant patients is only poorly understood. We investigated the impact of TacIPV on de novo donor-specific HLA antibodies (dnDSA) development and allograft rejection in Caucasian pediatric recipients of a living...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395307/ https://www.ncbi.nlm.nih.gov/pubmed/35166920 http://dx.doi.org/10.1007/s00467-022-05426-3 |
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author | Baghai Arassi, Maral Gauche, Laura Schmidt, Jeremy Höcker, Britta Rieger, Susanne Süsal, Caner Tönshoff, Burkhard Fichtner, Alexander |
author_facet | Baghai Arassi, Maral Gauche, Laura Schmidt, Jeremy Höcker, Britta Rieger, Susanne Süsal, Caner Tönshoff, Burkhard Fichtner, Alexander |
author_sort | Baghai Arassi, Maral |
collection | PubMed |
description | BACKGROUND: Tacrolimus (Tac) intraindividual variability (TacIPV) in pediatric kidney transplant patients is only poorly understood. We investigated the impact of TacIPV on de novo donor-specific HLA antibodies (dnDSA) development and allograft rejection in Caucasian pediatric recipients of a living or deceased donor kidney with low immunological risk. METHODS: This was a single-center retrospective study including 48 pediatric kidney transplant recipients. TacIPV was calculated based on coefficient of variation (CV%) 6–12 months posttransplant. TacIPV cutoff was set at the median (25%). Outcome parameters were dnDSA development and rejection episodes. RESULTS: In total, 566 Tac levels were measured with median 11.0 (6.0–17.0) measurements per patient. The cutoff of 25% corresponded to the median CV% in our study cohort (25%, IQR 18–35%) and was comparable to cutoffs determined by receiver operating characteristic (ROC) curve analysis. High TacIPV was associated with higher risk of dnDSA development (HR 3.4, 95% CI 1.0–11.1, P = 0.047; Kaplan–Meier analysis P = 0.018) and any kind of rejection episodes (HR 4.1, 95% CI 1.1–14.8, P = 0.033; Kaplan–Meier analysis P = 0.010). There was a clear trend towards higher TacIPV below the age of 6 years. TacIPV (CV%) was stable over time. A TacIPV (CV%) cutoff of 30% or IPV quantification by mean absolute deviation (MAD) showed comparable results. CONCLUSIONS: High TacIPV is associated with an increased risk of dnDSA development and rejection episodes > year 1 posttransplant even in patients with low immunological risk profile. Therefore, in patients with high TacIPV, potential causes should be addressed, and if not resolved, changes in immunosuppressive therapy should be considered. GRAPHICAL ABSTRACT: A higher resolution version of the Graphical abstract is available as Supplementary information. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-022-05426-3. |
format | Online Article Text |
id | pubmed-9395307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-93953072022-08-24 Association of intraindividual tacrolimus variability with de novo donor-specific HLA antibody development and allograft rejection in pediatric kidney transplant recipients with low immunological risk Baghai Arassi, Maral Gauche, Laura Schmidt, Jeremy Höcker, Britta Rieger, Susanne Süsal, Caner Tönshoff, Burkhard Fichtner, Alexander Pediatr Nephrol Original Article BACKGROUND: Tacrolimus (Tac) intraindividual variability (TacIPV) in pediatric kidney transplant patients is only poorly understood. We investigated the impact of TacIPV on de novo donor-specific HLA antibodies (dnDSA) development and allograft rejection in Caucasian pediatric recipients of a living or deceased donor kidney with low immunological risk. METHODS: This was a single-center retrospective study including 48 pediatric kidney transplant recipients. TacIPV was calculated based on coefficient of variation (CV%) 6–12 months posttransplant. TacIPV cutoff was set at the median (25%). Outcome parameters were dnDSA development and rejection episodes. RESULTS: In total, 566 Tac levels were measured with median 11.0 (6.0–17.0) measurements per patient. The cutoff of 25% corresponded to the median CV% in our study cohort (25%, IQR 18–35%) and was comparable to cutoffs determined by receiver operating characteristic (ROC) curve analysis. High TacIPV was associated with higher risk of dnDSA development (HR 3.4, 95% CI 1.0–11.1, P = 0.047; Kaplan–Meier analysis P = 0.018) and any kind of rejection episodes (HR 4.1, 95% CI 1.1–14.8, P = 0.033; Kaplan–Meier analysis P = 0.010). There was a clear trend towards higher TacIPV below the age of 6 years. TacIPV (CV%) was stable over time. A TacIPV (CV%) cutoff of 30% or IPV quantification by mean absolute deviation (MAD) showed comparable results. CONCLUSIONS: High TacIPV is associated with an increased risk of dnDSA development and rejection episodes > year 1 posttransplant even in patients with low immunological risk profile. Therefore, in patients with high TacIPV, potential causes should be addressed, and if not resolved, changes in immunosuppressive therapy should be considered. GRAPHICAL ABSTRACT: A higher resolution version of the Graphical abstract is available as Supplementary information. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-022-05426-3. Springer Berlin Heidelberg 2022-02-15 2022 /pmc/articles/PMC9395307/ /pubmed/35166920 http://dx.doi.org/10.1007/s00467-022-05426-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Baghai Arassi, Maral Gauche, Laura Schmidt, Jeremy Höcker, Britta Rieger, Susanne Süsal, Caner Tönshoff, Burkhard Fichtner, Alexander Association of intraindividual tacrolimus variability with de novo donor-specific HLA antibody development and allograft rejection in pediatric kidney transplant recipients with low immunological risk |
title | Association of intraindividual tacrolimus variability with de novo donor-specific HLA antibody development and allograft rejection in pediatric kidney transplant recipients with low immunological risk |
title_full | Association of intraindividual tacrolimus variability with de novo donor-specific HLA antibody development and allograft rejection in pediatric kidney transplant recipients with low immunological risk |
title_fullStr | Association of intraindividual tacrolimus variability with de novo donor-specific HLA antibody development and allograft rejection in pediatric kidney transplant recipients with low immunological risk |
title_full_unstemmed | Association of intraindividual tacrolimus variability with de novo donor-specific HLA antibody development and allograft rejection in pediatric kidney transplant recipients with low immunological risk |
title_short | Association of intraindividual tacrolimus variability with de novo donor-specific HLA antibody development and allograft rejection in pediatric kidney transplant recipients with low immunological risk |
title_sort | association of intraindividual tacrolimus variability with de novo donor-specific hla antibody development and allograft rejection in pediatric kidney transplant recipients with low immunological risk |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395307/ https://www.ncbi.nlm.nih.gov/pubmed/35166920 http://dx.doi.org/10.1007/s00467-022-05426-3 |
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