Deceased donor urinary Dickkopf-3 associates with future allograft function following kidney transplantation

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Jonathan de Fallois - , University Hospital Leipzig (Author)
  • Anna Günzel - , University Hospital Leipzig (Author)
  • Christoph Daniel - , University Hospital at the Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Julian Stumpf - , Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden (Author)
  • Martin Busch - , Jena University Hospital (Author)
  • Ulrich Pein - , Martin Luther University Hospital (Author)
  • Alexander Paliege - , Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden (Author)
  • Kerstin Amann - , University Hospital at the Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Thorsten Wiech - , University Hospital Hamburg Eppendorf (Author)
  • Elena Hantmann - , University Hospital Leipzig, Charité – Universitätsmedizin Berlin (Author)
  • Gunter Wolf - , Jena University Hospital (Author)
  • Felix Pfeifer - , German Organ Procurement Organization (DSO), Region East (Author)
  • Matthias Girndt - , Martin Luther University Hospital (Author)
  • Tom H Lindner - , University Hospital Leipzig (Author)
  • Antje Weimann - , University Hospital Leipzig (Author)
  • Daniel Seehofer - , University Hospital Leipzig (Author)
  • Anette Bachmann - , University Hospital Leipzig (Author)
  • Klemens Budde - , Charité – Universitätsmedizin Berlin (Author)
  • Ronald Biemann - , University Hospital Leipzig (Author)
  • Berend Isermann - , University Hospital Leipzig (Author)
  • Christoph Engel - , Leipzig University (Author)
  • Katalin Dittrich - , University Hospital Leipzig (Author)
  • Christian Hugo - , Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden (Author)
  • Jan Halbritter - , University Hospital Leipzig, Charité – Universitätsmedizin Berlin (Author)

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.

Details

Original languageEnglish
Pages (from-to)516-530
Number of pages15
JournalAmerican Journal of Transplantation
Volume25
Issue number3
Early online date19 Sept 2024
Publication statusPublished - Mar 2025
Peer-reviewedYes

External IDs

Scopus 85206002630

Keywords

Keywords

  • DKK3, biomarker, donor, kidney transplantation, recipient