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Biomarker prediction of delayed graft function and prognosis post-kidney transplantation

Lookup NU author(s): Professor Neil SheerinORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Introduction. Aminoacylase-1 (ACY1) and additional biomarkers were evaluated for prediction of delayed graft function (DGF) and prognosis following kidney transplantation. Methods. Serum biomarkers were measured (days 1-2 post-transplant for DGF prediction and 1-3 for prognosis) in 237 patients transplanted in Leeds (2003-11) in the discovery phase and 319 patients from 7 UK transplant centres (2012-16) in the validation phase with median follow-up of 13.28 years (12.4-13.8 IQR) and 9.03 years (IQR 5.19-10.16) respectively. Results. DGF occurred in 29.5% and 18.2% of patients in the discovery and validation cohorts respectively. A DGF linear predictor combining ACY1, soluble tumour necrosis factor receptor 1 (TNFR1) and cystatin C (CysC) demonstrated an AUROC of 0.93, decreasing to 0.83 in the validation phase. Comparable values for the individual components were ACY1 (0.79 vs 0.65), sTNFR1 (0.88 vs 0.89) and CysC (0.89 vs 0.82) and 0.75 vs 0.81 for creatinine (Cr) as the gold standard. The prognostic linear predictor variables for death-censored graft survival (DCGS) were CysC, ACY1, midkine and recipient age at transplant but k-statistic values of 0.55 in all transplants and 0.52 in deceased donor kidney transplants (DDKT) precluded validation. Individually sTNFR1, CysC and Cr were all significantly associated with DCGS across both discovery and validation phases and preliminary findings indicated ACY-1 and CysC were consistently associated with DCGS in DDKTs affected by DGF. Impacts of changes in clinical practice across the two phases and biomarker performance are described. Conclusion. Several biomarkers show potential as predictors of DGF or outcome and should be explored further in larger studies.


Publication metadata

Author(s): Banks RE, Wilson M, WelberrySmith M, Lewington AJP, Kurth MJ, Sewell H, Bartle R, Watt JM, Ruddock MW, McAleer D, Winter H, Gibbs P, Sheerin NS, Jones C, Stoves J, Ridgway D, McKane WS, Edwards A, Bhandhari S, Edey M, Thompson D, Lippiatt CM, Selby PJ

Publication type: Article

Publication status: Published

Journal: Kidney International Reports

Year: 2025

Issue: ePub ahead of Print

Online publication date: 05/11/2025

Acceptance date: 28/10/2025

Date deposited: 29/10/2025

ISSN (electronic): 2468-0249

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.ekir.2025.10.021

DOI: 10.1016/j.ekir.2025.10.021

Data Access Statement: In line with the ethical approval granted to the Leeds Multidisciplinary RTB and NIHR BioRTB, requests for access to the biomarker data together with relevant associated clinical data can be made by application to the Leeds Joint RTB Management Group. Proposal forms can be accessed by email (rtb@leeds.ac.uk). Each application will be considered on a case-by-case basis, based on research question and analysis plans. Data will only be released for those patients who have consented to data sharing and all data will be fully deidentified.


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Funding

Funder referenceFunder name
Innovate UK Technology Strategy Board (grant reference 74465-503294, “Biomarkers for patient assessment and stratification post-renal transplantation BioPAsSPoRT” study)
Randox Laboratories Ltd
the Department of Health SBRI Kidney Care grant scheme (grant reference KCSBRI-031)
the National Institute for Health Research Programme Grants for Applied Research programme with one component being the NIHR BioRTB which provided samples (grant reference NIHR PGfAR RP-PG-0707–10101)

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