Quantifying measurement uncertainty in renal transplant biopsy assessment

Abstract

Introduction: Renal transplant biopsies provide insights into graft health and support decision making. The current evidence on links between biopsy scores and transplant outcomes suggests there may be numerous factors affecting biopsy scores. Here we adopt measurement science approach to investigate the sources of uncertainty in biopsy assessment and suggest techniques to improve its robustness.

Methods: Histological assessments, Remuzzi scores, biopsy processing and clinical variables are obtained from 144 repeat biopsies originating from 16 deceased-donor kidneys. We conducted sensitivity analysis to find the morphometric features with highest discriminating power and studied the dependencies of these features on biopsy and stain type. The analysis results formed a basis for recommendations on reducing the assessment variability.

Results: Most morphometric variables are influenced by the biopsy and stain types. The variables with the highest discriminatory power are sclerotic glomeruli counts, healthy glomeruli counts per unit area, percentages of interstitial fibrosis and tubular atrophy as well as diameter and lumen of the worst artery. A revised glomeruli adequacy score is proposed to improve the robustness of the glomeruli statistics, whereby a minimum of 104 µm² of cortex tissue is recommended to keep type 1 and type 2 error probabilities below 0.15 and 0.2.

Discussion: The findings are transferable to several biopsy scoring systems. We hope that this work will help practitioners to understand the sources of statistical uncertainty and improve the utility of renal biopsy.

Keywords: Remuzzi score; glomerular adequacy; measurement uncertainty; pre-transplantation biopsy; reproducibility; sensitivity analysis.

Figure 1

Biopsy acquisition and image selection.

Figure 2

Data processing and analysis steps.

Figure 3

Percentage of GS (top-left), wall thickness to lumen ratio (top-right), percentage of TA (bottom-left), and percentage of IF (bottom-right) grouped by kidney. Left/right Kidneys from the same donor share a number (PL1/PR1). The background colour separates the associated Remuzzi sub-scores ranging from 0 (bottom) to 3 (top).

Figure 4

Dependencies between morphometric (left) and biopsy processing (right) variables. Colour band thickness is proportional to statistical significance (p<0.001 for all pairs).

Figure 5

Cumulative distribution functions of glomeruli counts per unit area (in µm^-2) by biopsy technique. Only the biopsies without medulla (cortex-only biopsies) are considered.