Jonathan de Fallois , Anna Günzel , Christoph Daniel , Julian Stumpf , Martin Busch , Ulrich Pein , Alexander Paliege , Kerstin Amann , Thorsten Wiech , Elena Hantmann , Gunter Wolf , Felix Pfeifer , Matthias Girndt , Tom H. Lindner , Antje Weimann , Daniel Seehofer , Anette Bachmann , Klemens Budde , Ronald Biemann , Berend Isermann , Jan Halbritter
{"title":"Deceased donor urinary Dickkopf-3 associates with future allograft function following kidney transplantation","authors":"Jonathan de Fallois , Anna Günzel , Christoph Daniel , Julian Stumpf , Martin Busch , Ulrich Pein , Alexander Paliege , Kerstin Amann , Thorsten Wiech , Elena Hantmann , Gunter Wolf , Felix Pfeifer , Matthias Girndt , Tom H. Lindner , Antje Weimann , Daniel Seehofer , Anette Bachmann , Klemens Budde , Ronald Biemann , Berend Isermann , Jan Halbritter","doi":"10.1016/j.ajt.2024.09.016","DOIUrl":null,"url":null,"abstract":"<div><div>Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/crea ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Prenephrectomy uDKK3/crea levels were 100× higher in deceased than in living donors (9888 pg/mg vs 113 pg/mg; <em>P</em> < .001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, <em>n</em> = 68) or above (group B, <em>n</em> = 65) median. The primary end point of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 mL/min/1.73 m<sup>2</sup>) than that in group B (44.2 mL/min/1.73 m<sup>2</sup>; <em>P</em> = .0139). Second, the composite clinical end point consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modeling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of −4.282 mL/min/1.73 m<sup>2</sup> per logarithmic increase in donor uDKK3/crea. In summary, uDKK3 may serve as a noninvasive, donor-dependent biomarker for assessing organ quality and future allograft function.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 3","pages":"Pages 516-530"},"PeriodicalIF":8.2000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Transplantation","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1600613524005719","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0
Abstract
Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/crea ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Prenephrectomy uDKK3/crea levels were 100× higher in deceased than in living donors (9888 pg/mg vs 113 pg/mg; P < .001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, n = 68) or above (group B, n = 65) median. The primary end point of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 mL/min/1.73 m2) than that in group B (44.2 mL/min/1.73 m2; P = .0139). Second, the composite clinical end point consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modeling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of −4.282 mL/min/1.73 m2 per logarithmic increase in donor uDKK3/crea. In summary, uDKK3 may serve as a noninvasive, donor-dependent biomarker for assessing organ quality and future allograft function.
期刊介绍:
The American Journal of Transplantation is a leading journal in the field of transplantation. It serves as a forum for debate and reassessment, an agent of change, and a major platform for promoting understanding, improving results, and advancing science. Published monthly, it provides an essential resource for researchers and clinicians worldwide.
The journal publishes original articles, case reports, invited reviews, letters to the editor, critical reviews, news features, consensus documents, and guidelines over 12 issues a year. It covers all major subject areas in transplantation, including thoracic (heart, lung), abdominal (kidney, liver, pancreas, islets), tissue and stem cell transplantation, organ and tissue donation and preservation, tissue injury, repair, inflammation, and aging, histocompatibility, drugs and pharmacology, graft survival, and prevention of graft dysfunction and failure. It also explores ethical and social issues in the field.