Loizeau, X; Romanchikova, M; Thomas, S A; Alsuleman, M; Ayorinde, J O O; Pettigrew, G J (2024) Quantifying measurement uncertainty in renal transplant biopsy assessment. Frontiers in Nephrology, 4. 1458491

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Abstract

Background

Renal transplant biopsies provide insights into both function and structure and are being increasingly used as a clinical decision-making tool to assess graft health. Various scoring systems such as the Remuzzi score can be used to evaluate kidney health using tissue morphology information on the slide. However, variability in sample preparation, imaging and pathology assessment has been shown to impact the score. Our work uses the measurement science approach to establish the sources of the measurement uncertainty in the biopsy assessment process and to provide practical recommendations to improve the statistical robustness and diagnostic power of the score.

Methods

We used the kidney assessment data from 144 repeat biopsies acquired from 16 discarded kidneys of 12 deceased donors. The morphometric features of biopsy images most strongly linked with kidney health were identified using sensitivity analysis. Dependencies between the biopsy processing steps, the morphometric features and the subsequent Remuzzi scores were investigated using statistical dependence testing. Recommendations aiming to reduce the uncertainty of the useful morphometric variables most strongly affected by the biopsy processing steps were provided.

Results

The reproducibility of the morphometric variables and Remuzzi scores is affected by the biopsy extraction and staining methods. Numbers of all and healthy glomeruli per unit area, percentages of interstitial fibrosis and tubular atrophy, diameter of the worst artery and its lumen were found to have the strongest association with the estimator of kidney health. A revision of the glomeruli adequacy score is proposed to improve the robustness of glomeruli statistics.

Discussion

Number of healthy glomeruli per unit area, percentage of interstitial fibrosis and tubular atrophy, and lumen diameter have shown to be potentially useful indicators of kidney health. Normalisation methods to mitigate the impact of biopsy extraction and staining should be developed to aid data harmonisation. Our results suggest that at least 156μm2 of cortex tissue are required to achieve reliable assessment.

Item Type:	Article
Keywords:	pre-transplantation biopsy, Remuzzi score, measurement uncertainty, reproducibility, glomerular adequacy, sensitivity analysis
Subjects:	Mathematics and Scientific Computing > Measurement Uncertainties
Divisions:	Data Science
Identification number/DOI:	10.3389/fneph.2024.1458491
Last Modified:	30 Jul 2025 14:24
URI:	https://eprintspublications.npl.co.uk/id/eprint/10214