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Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort

BACKGROUND. Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the...

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Autores principales: Ekberg, Jana, Hjelmberg, Marie, Norén, Åsa, Brännström, Mats, Herlenius, Gustaf, Baid-Agrawal, Seema
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540914/
https://www.ncbi.nlm.nih.gov/pubmed/37781170
http://dx.doi.org/10.1097/TXD.0000000000001525
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author Ekberg, Jana
Hjelmberg, Marie
Norén, Åsa
Brännström, Mats
Herlenius, Gustaf
Baid-Agrawal, Seema
author_facet Ekberg, Jana
Hjelmberg, Marie
Norén, Åsa
Brännström, Mats
Herlenius, Gustaf
Baid-Agrawal, Seema
author_sort Ekberg, Jana
collection PubMed
description BACKGROUND. Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the absence of lifelong immunosuppression and is performed in young healthy participants. Therefore, UTx provides a unique setting for evaluating the effect of time-limited calcineurin inhibitors treatment on recipients’ kidney function. METHODS. In the first UTx cohort worldwide, we studied kidney function using estimated glomerular filtration rate (eGFR) in 7 women over a median follow-up of 121 (119–126) mo. RESULTS. Median eGFR (mL/min/1.73 m(2)) of the cohort was 113 at UTx, which declined to 74 during month 3, 71 at months 10–12, 76 at hysterectomy (HE), and 83 at last follow-up. Median duration of tacrolimus exposure was 52 (22–83) mo, and median trough levels (µg/L) were 10 during month 3 and 5.8 at HE. Between UTx and month 3, decline in kidney function was observed in all 7 participants with a median eGFR slope for the whole cohort of −24 mL/min/1.73 m(2), which declined further by −4 mL/min/1.73 m(2) until months 10–12. Thereafter, eGFR slope improved in 3 participants, remained stable in 3, and worsened in 1 until HE/tacrolimus discontinuation, after which it improved in 2. Eventually, between UTx and last follow-up, 4 of 7 participants had a decline in their eGFR, the median annual eGFR slope being negative at −1.9 mL/min/1.73 m(2)/y for the whole group. CONCLUSIONS. Kidney function declined in all recipients early after UTx followed by a persistent long-term decrease in majority, despite transplantectomy and discontinuation of immunosuppression. Thus, UTx may incur an increased risk of chronic kidney disease even in this young and healthy population, highlighting the importance of close surveillance of kidney function and minimization of tacrolimus exposure.
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spelling pubmed-105409142023-09-30 Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort Ekberg, Jana Hjelmberg, Marie Norén, Åsa Brännström, Mats Herlenius, Gustaf Baid-Agrawal, Seema Transplant Direct Hand and Composite Tissue Allotransplantation BACKGROUND. Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the absence of lifelong immunosuppression and is performed in young healthy participants. Therefore, UTx provides a unique setting for evaluating the effect of time-limited calcineurin inhibitors treatment on recipients’ kidney function. METHODS. In the first UTx cohort worldwide, we studied kidney function using estimated glomerular filtration rate (eGFR) in 7 women over a median follow-up of 121 (119–126) mo. RESULTS. Median eGFR (mL/min/1.73 m(2)) of the cohort was 113 at UTx, which declined to 74 during month 3, 71 at months 10–12, 76 at hysterectomy (HE), and 83 at last follow-up. Median duration of tacrolimus exposure was 52 (22–83) mo, and median trough levels (µg/L) were 10 during month 3 and 5.8 at HE. Between UTx and month 3, decline in kidney function was observed in all 7 participants with a median eGFR slope for the whole cohort of −24 mL/min/1.73 m(2), which declined further by −4 mL/min/1.73 m(2) until months 10–12. Thereafter, eGFR slope improved in 3 participants, remained stable in 3, and worsened in 1 until HE/tacrolimus discontinuation, after which it improved in 2. Eventually, between UTx and last follow-up, 4 of 7 participants had a decline in their eGFR, the median annual eGFR slope being negative at −1.9 mL/min/1.73 m(2)/y for the whole group. CONCLUSIONS. Kidney function declined in all recipients early after UTx followed by a persistent long-term decrease in majority, despite transplantectomy and discontinuation of immunosuppression. Thus, UTx may incur an increased risk of chronic kidney disease even in this young and healthy population, highlighting the importance of close surveillance of kidney function and minimization of tacrolimus exposure. Lippincott Williams & Wilkins 2023-09-28 /pmc/articles/PMC10540914/ /pubmed/37781170 http://dx.doi.org/10.1097/TXD.0000000000001525 Text en Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Hand and Composite Tissue Allotransplantation
Ekberg, Jana
Hjelmberg, Marie
Norén, Åsa
Brännström, Mats
Herlenius, Gustaf
Baid-Agrawal, Seema
Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort
title Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort
title_full Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort
title_fullStr Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort
title_full_unstemmed Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort
title_short Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort
title_sort long-term course of kidney function in uterus transplant recipients under treatment with tacrolimus and after transplantectomy: results of the first clinical cohort
topic Hand and Composite Tissue Allotransplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540914/
https://www.ncbi.nlm.nih.gov/pubmed/37781170
http://dx.doi.org/10.1097/TXD.0000000000001525
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