Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection

Background. Preimplantation biopsy combines measurements of injury into a composite index to inform organ acceptance. The uncertainty in these measurements remains poorly characterized, raising concerns variability may contribute to inappropriate clinical decisions. Methods. We adopted a metrologica...

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Main Authors: John O.O. Ayorinde, MD (UK), Xavier Loizeau, PhD, Victoria Bardsley, MBBS (UK), Spencer Angus Thomas, PhD, Marina Romanchikova, PhD, Alex Samoshkin, PhD, Gavin J. Pettigrew, MD (UK)
Format: Article
Language:English
Published: Wolters Kluwer 2024-11-01
Series:Transplantation Direct
Online Access:http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001708
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author John O.O. Ayorinde, MD (UK)
Xavier Loizeau, PhD
Victoria Bardsley, MBBS (UK)
Spencer Angus Thomas, PhD
Marina Romanchikova, PhD
Alex Samoshkin, PhD
Gavin J. Pettigrew, MD (UK)
author_facet John O.O. Ayorinde, MD (UK)
Xavier Loizeau, PhD
Victoria Bardsley, MBBS (UK)
Spencer Angus Thomas, PhD
Marina Romanchikova, PhD
Alex Samoshkin, PhD
Gavin J. Pettigrew, MD (UK)
author_sort John O.O. Ayorinde, MD (UK)
collection DOAJ
description Background. Preimplantation biopsy combines measurements of injury into a composite index to inform organ acceptance. The uncertainty in these measurements remains poorly characterized, raising concerns variability may contribute to inappropriate clinical decisions. Methods. We adopted a metrological approach to evaluate biopsy score reliability. Variability was assessed by performing repeat biopsies (n = 293) on discarded allografts (n = 16) using 3 methods (core, punch, and wedge). Uncertainty was quantified using a bootstrapping analysis. Observer effects were controlled by semi-blinded scoring, and the findings were validated by comparison with standard glass evaluation. Results. The surgical method strongly determined the size (core biopsy area 9.04 mm2, wedge 37.9 mm2) and, therefore, yield (glomerular yield r = 0.94, arterial r = 0.62) of each biopsy. Core biopsies yielded inadequate slides most frequently. Repeat biopsy of the same kidney led to marked variation in biopsy scores. In 10 of 16 cases, scores were contradictory, crossing at least 1 decision boundary (ie, to transplant or to discard). Bootstrapping demonstrated significant uncertainty associated with single-slide assessment; however, scores were similar for paired kidneys from the same donor. Conclusions. Our investigation highlights the risks of relying on single-slide assessment to quantify organ injury. Biopsy evaluation is subject to uncertainty, meaning each slide is better conceptualized as providing an estimate of the kidney’s condition rather than a definitive result. Pooling multiple assessments could improve the reliability of biopsy analysis, enhancing confidence. Where histological quantification is necessary, clinicians should seek to develop new protocols using more tissue and consider automated methods to assist pathologists in delivering analysis within clinical time frames.
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spelling doaj-art-0c0d14c93e68481784a48754d959de4d2025-08-20T01:53:26ZengWolters KluwerTransplantation Direct2373-87312024-11-011011e170810.1097/TXD.0000000000001708202411000-00003Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ SelectionJohn O.O. Ayorinde, MD (UK)0Xavier Loizeau, PhD1Victoria Bardsley, MBBS (UK)2Spencer Angus Thomas, PhD3Marina Romanchikova, PhD4Alex Samoshkin, PhD5Gavin J. Pettigrew, MD (UK)61 Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom.2 National Physical Laboratory, Teddington, United Kingdom.3 Department of Histopathology, Addenbrooke’s Hospital, Cambridge, United Kingdom.2 National Physical Laboratory, Teddington, United Kingdom.2 National Physical Laboratory, Teddington, United Kingdom.4 Office for Translational Research, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.1 Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom.Background. Preimplantation biopsy combines measurements of injury into a composite index to inform organ acceptance. The uncertainty in these measurements remains poorly characterized, raising concerns variability may contribute to inappropriate clinical decisions. Methods. We adopted a metrological approach to evaluate biopsy score reliability. Variability was assessed by performing repeat biopsies (n = 293) on discarded allografts (n = 16) using 3 methods (core, punch, and wedge). Uncertainty was quantified using a bootstrapping analysis. Observer effects were controlled by semi-blinded scoring, and the findings were validated by comparison with standard glass evaluation. Results. The surgical method strongly determined the size (core biopsy area 9.04 mm2, wedge 37.9 mm2) and, therefore, yield (glomerular yield r = 0.94, arterial r = 0.62) of each biopsy. Core biopsies yielded inadequate slides most frequently. Repeat biopsy of the same kidney led to marked variation in biopsy scores. In 10 of 16 cases, scores were contradictory, crossing at least 1 decision boundary (ie, to transplant or to discard). Bootstrapping demonstrated significant uncertainty associated with single-slide assessment; however, scores were similar for paired kidneys from the same donor. Conclusions. Our investigation highlights the risks of relying on single-slide assessment to quantify organ injury. Biopsy evaluation is subject to uncertainty, meaning each slide is better conceptualized as providing an estimate of the kidney’s condition rather than a definitive result. Pooling multiple assessments could improve the reliability of biopsy analysis, enhancing confidence. Where histological quantification is necessary, clinicians should seek to develop new protocols using more tissue and consider automated methods to assist pathologists in delivering analysis within clinical time frames.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001708
spellingShingle John O.O. Ayorinde, MD (UK)
Xavier Loizeau, PhD
Victoria Bardsley, MBBS (UK)
Spencer Angus Thomas, PhD
Marina Romanchikova, PhD
Alex Samoshkin, PhD
Gavin J. Pettigrew, MD (UK)
Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection
Transplantation Direct
title Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection
title_full Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection
title_fullStr Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection
title_full_unstemmed Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection
title_short Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection
title_sort measurement matters a metrological approach to renal preimplantation biopsy evaluation to address uncertainty in organ selection
url http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001708
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