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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025Background: Pre-implantation biopsy may help select kidneys retrieved from elderly deceased donors for transplantation, but concerns persist that it may cause unnecessary discard of kidneys that would have provided acceptable transplant function. The PITHIA trial tested the hypothesis that introduction of a National Digital Pathology Service (NDPS) would increase the proportion of kidneys transplanted from elderly donors and/or improve their function. Methods: A stepped-wedge cluster randomised controlled registry trial delivered the NDPS to 22 UK kidney transplant centres (clusters) in 5 sequences at four-monthly intervals, using a restricted randomisation technique to ensure similar cluster sizes in the intervention and control status. Upon access to the intervention, centres could request urgent pre-implantation biopsy on kidneys from deceased donors aged 60 years or older. Co-primary outcome measures were the proportion of kidneys transplanted upon first offer according to whether the centre had access or not to the biopsy service, and the 1-year eGFR of the kidneys that were transplanted. Analysis adjusts for clustering and underlying secular trends, with 97.5% Confidence Intervals (CI) reported to reflect the two co-primary outcomes. The trial is complete (Trial Registration Number: ISRCTN 11708741). Findings: The trial commenced on 1st October 2018 and ended on 31st January 2022. Of the 2502 eligible kidneys offered, 1355 single and 67 dual transplants were performed. Regarding the first primary endpoint, a non-significantly lower proportion of those kidneys first offered to centres with access to the biopsy service were transplanted compared with those offered to centres without access (295 of 1241 (23.8%) vs. 377 of 1261 (29.9%): adjusted Odds Ratio (97.5% CI) 0.91 (0.60–1.39); p = 0.6083). For the second primary endpoint, the adjusted mean (SE) 1-year eGFR of the transplant kidneys was similar, irrespective of whether the implanting centre had access to the biopsy service or not (43.7 (1.3) ml/min/1.73 m2 vs. 42.2 (1.3) ml/min/1.73 m2; adjusted mean difference (97.5% CI) 1.53 (−2.33 to 5.40); p = 0.37). Secondary outcome analysis of how the biopsy service was adopted revealed that biopsies were performed on 287 of the 1493 (19.2%) kidneys offered to at least one centre with access to the biopsy service, with marked variation between transplant centres in requests for biopsy, and in implantation rates of biopsied kidneys. Nevertheless, 191 (66.6%) of biopsied kidneys were transplanted, compared with 643 of the 1009 (63.7%) kidneys only ever offered to centres without biopsy access, and 588 of the 1206 (48.8%) kidneys that were not biopsied, despite being offered to at least one centre with biopsy access. Interpretation: Implementation of the NDPS did not significantly increase transplantation rates of elderly deceased donor kidneys upon first offer, nor improve 1-year eGFR of the transplanted kidneys. This may reflect inter-centre variation in adoption and application of the biopsy service; such variations would need to be considered when designing future studies of pre-implantation biopsy analysis. Funding: NIHR Research for Patient Benefit programme (RfPB PB-PG-1215-20033).
Author(s): Summers DM, Ayorinde JOO, Neil DA, Hemming K, Smith L, Mehew J, Thomas H, Brown R, Phillips S, Laing E, Sidders A, Deary AJ, Johnson RJ, Bardsley V, Thiru S, Griffiths MH, Perera R, Cain O, Roufosse C, Simmonds N, Sheaff M, Brearley N, Vydianath B, Paterson A, Gopalakrishnan K, Chatzitolios A, Callaghan CJ, Jarvis R, Dor FJMF, Dutta S, Bagul A, Wilson C, Ridgway D, Barlow A, Baker R, Sharif A, McDaid J, Terrace J, Marson L, Roy D, Hunter J, Szabo L, Knight S, Stevenson K, Mark P, Turner S, Moinuddin Z, Ghazanfar A, Sivaprakasam R, Motallebzadeh R, Torpey N, Jones G, Boffa C, Gibbs P, Connor A, Saif I, Shrestha B, Hill H, Fotheringham J, Pettigrew GJ
Publication type: Article
Publication status: Published
Journal: The Lancet Regional Health - Europe
Year: 2025
Volume: 56
Print publication date: 01/09/2025
Online publication date: 22/07/2025
Acceptance date: 03/07/2025
Date deposited: 04/08/2025
ISSN (electronic): 2666-7762
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.lanepe.2025.101390
DOI: 10.1016/j.lanepe.2025.101390
Data Access Statement: Individual participant data that underlie the results reported in this article will be available, after de-identification (text, tables, figures, and appendices) to researchers who provide a methodologically sound proposal with pre-defined aims. The study protocol, statistical analysis plan and analytic code will also be available. Data will be available from three months following article. Proposals should be directed to gjp25@cam.ac.uk; to gain access, data requestors will need to sign a data access agreement. If UK Transplant Registry Data is required, additional approval from the relevant NHS Blood and Transplant research group will be sought upon receipt of a data sharing request form.
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