Summers Dominic M, Ayorinde John O O, Neil Desley A, Hemming Karla, Smith Laura, Mehew Jennifer, Thomas Helen, Brown Rosie, Phillips Suzie, Laing Emma, Sidders Anna, Deary Alison J, Johnson Rachel J, Bardsley Victoria, Thiru Sathia, Griffiths Meryl H, Perera Ranmith, Cain Owen, Roufosse Candice, Simmonds Naomi, Sheaff Michael, Brearley Natalie, Vydianath Bindu, Paterson Anna, Gopalakrishnan Kishore, Chatzitolios Anastasios, Callaghan Chris J, Jarvis Richard, Dor Frank J M F, Dutta Smarajit, Bagul Atul, Wilson Colin, Ridgway Dan, Barlow Adam, Baker Richard, Sharif Adnan, McDaid James, Terrace John, Marson Lorna, Roy Debabrata, Hunter James, Szabo Laszlo, Knight Simon, Stevenson Karen, Mark Patrick, Turner Samuel, Moinuddin Zia, Ghazanfar Abbas, Sivaprakasam Rajesh, Motallebzadeh Reza, Torpey Nicholas, Jones Gareth, Boffa Catherine, Gibbs Paul, Connor Andrew, Saif Imran, Shrestha Badri, Hill Harry, Fotheringham James, Pettigrew Gavin J
Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
NIHR Clinical Lecturer, University College London, UK.
Lancet Reg Health Eur. 2025 Jul 22;56:101390. doi: 10.1016/j.lanepe.2025.101390. eCollection 2025 Sep.
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.
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).
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 m vs. 42.2 (1.3) ml/min/1.73 m; 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.
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.
NIHR Research for Patient Benefit programme (RfPB PB-PG-1215-20033).
植入前活检可能有助于挑选出老年已故供体的肾脏用于移植，但人们一直担心这可能会导致不必要地丢弃原本可提供可接受移植功能的肾脏。PITHIA试验检验了这样一个假设，即引入国家数字病理服务（NDPS）会提高老年供体肾脏的移植比例和/或改善其功能。
一项阶梯式楔形整群随机对照注册试验分5个序列、每隔4个月向22个英国肾脏移植中心（整群）提供NDPS，采用受限随机化技术以确保干预组和对照组的整群规模相似。一旦可以使用该干预措施，各中心可要求对60岁及以上已故供体的肾脏进行紧急植入前活检。共同主要结局指标为根据中心是否可使用活检服务，首次提供的肾脏中被移植的比例，以及移植肾脏的1年估算肾小球滤过率（eGFR）。分析对整群效应和潜在长期趋势进行了校正，报告的97.5%置信区间（CI）反映两个共同主要结局。该试验已完成（试验注册号：ISRCTN 11708741）。
该试验于2018年10月1日开始，2022年1月31日结束。在提供的2502个符合条件的肾脏中，进行了1355例单肾移植和67例双肾移植。关于第一个主要终点，与提供给无法使用活检服务的中心的肾脏相比，首次提供给可使用活检服务中心的肾脏被移植的比例略低，但差异无统计学意义（1241个中的295个（23.8%）对1261个中的377个（29.9%）：校正优势比（97.5%CI）0.91（0.60 - 1.39）；p = 0.6083）。对于第二个主要终点，无论植入中心是否可使用活检服务，移植肾脏的校正平均（SE）1年eGFR相似（43.7（1.3）ml/min/1.73m对42.2（1.3）ml/min/1.73m；校正平均差异（97.5%CI）1.53（-2.33至5.40）；p = 0.37）。对活检服务采用情况的次要结局分析显示，在提供给至少一个可使用活检服务中心的1493个肾脏中，有287个（19.2%）进行了活检，各移植中心在活检请求和活检肾脏植入率方面存在显著差异。然而，活检肾脏中有191个（66.6%）被移植，相比之下，仅提供给无活检服务中心的1009个肾脏中有643个（63.7%）被移植，以及尽管提供给至少一个有活检服务的中心但未进行活检的1206个肾脏中有588个（48.8%）被移植。
实施NDPS并未显著提高首次提供的老年已故供体肾脏的移植率，也未改善移植肾脏的1年eGFR。这可能反映了各中心在活检服务采用和应用方面的差异；在设计未来的植入前活检分析研究时需要考虑这些差异。
英国国家卫生研究院患者受益研究计划（RfPB PB - PG - 1215 - 20033）。
