Quantifying Measurement Uncertainty in Renal Transplant Biopsy Assessment

Overview

Journal Front Nephrol

Specialty Nephrology

Date 2024 Oct 30

PMID 39473871

Authors

Xavier Loizeau

Marina Romanchikova

Spencer A Thomas

Moulham Alsuleman

John O O Ayorinde

Gavin J Pettigrew

Affiliations

Soon will be listed here.

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 µm 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.

References

Dahmen M, Becker F, Pavenstadt H, Suwelack B, Schutte-Nutgen K, Reuter S . Validation of the Kidney Donor Profile Index (KDPI) to assess a deceased donor's kidneys' outcome in a European cohort. Sci Rep. 2019; 9(1):11234. PMC: 6677881. DOI: 10.1038/s41598-019-47772-7. View

Munivenkatappa R, Schweitzer E, Papadimitriou J, Drachenberg C, Thom K, Perencevich E . The Maryland aggregate pathology index: a deceased donor kidney biopsy scoring system for predicting graft failure. Am J Transplant. 2008; 8(11):2316-24. DOI: 10.1111/j.1600-6143.2008.02370.x. View

Ayorinde J, Summers D, Pankhurst L, Laing E, Deary A, Hemming K . PreImplantation Trial of Histopathology In renal Allografts (PITHIA): a stepped-wedge cluster randomised controlled trial protocol. BMJ Open. 2019; 9(1):e026166. PMC: 6340453. DOI: 10.1136/bmjopen-2018-026166. View

Huang S, Lin Y, Wen M, Lin W, Fang P, Liang P . Unsatisfactory reproducibility of interstitial inflammation scoring in allograft kidney biopsy. Sci Rep. 2023; 13(1):7095. PMC: 10151326. DOI: 10.1038/s41598-023-33908-3. View

Chen K, Guntur G, Stalam T, Okonkwo N, Drachenberg C, Goussous N . Deceased-Donor Kidney Biopsy Scoring Systems for Predicting Future Graft Function: A Comparative Study. Transplant Proc. 2020; 53(3):906-912. DOI: 10.1016/j.transproceed.2020.09.002. View

Rao P, Schaubel D, Guidinger M, Andreoni K, Wolfe R, Merion R . A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index. Transplantation. 2009; 88(2):231-6. DOI: 10.1097/TP.0b013e3181ac620b. View

Haas M . Donor kidney biopsies: pathology matters, and so does the pathologist. Kidney Int. 2014; 85(5):1016-9. DOI: 10.1038/ki.2013.439. View

Corwin H, Schwartz M, Lewis E . The importance of sample size in the interpretation of the renal biopsy. Am J Nephrol. 1988; 8(2):85-9. DOI: 10.1159/000167563. View

Remuzzi G, Cravedi P, Perna A, Dimitrov B, Turturro M, Locatelli G . Long-term outcome of renal transplantation from older donors. N Engl J Med. 2006; 354(4):343-52. DOI: 10.1056/NEJMoa052891. View

10.

Villanego F, Vigara L, Cazorla J, Naranjo J, Atienza L, Garcia A . Evaluation of Expanded Criteria Donors Using the Kidney Donor Profile Index and the Preimplantation Renal Biopsy. Transpl Int. 2022; 35:10056. PMC: 9207180. DOI: 10.3389/ti.2022.10056. View

11.

Yong Z, Kipgen D, Aitken E, Khan K, Kingsmore D . Wedge Versus Core Biopsy at Time Zero: Which Provides Better Predictive Value for Delayed Graft Function With the Remuzzi Histological Scoring System?. Transplant Proc. 2015; 47(6):1605-9. DOI: 10.1016/j.transproceed.2015.03.050. View

12.

Solez K, Axelsen R, Benediktsson H, Burdick J, Cohen A, Colvin R . International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int. 1993; 44(2):411-22. DOI: 10.1038/ki.1993.259. View

13.

Ayorinde J, Loizeau X, Bardsley V, Thomas S, Romanchikova M, Samoshkin A . Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection. Transplant Direct. 2024; 10(11):e1708. PMC: 11469905. DOI: 10.1097/TXD.0000000000001708. View

14.

Eccher A, Becker J, Pagni F, Cazzaniga G, Rossi M, Gambaro G . The Puzzle of Preimplantation Kidney Biopsy Decision-Making Process: The Pathologist Perspective. Life (Basel). 2024; 14(2). PMC: 10890315. DOI: 10.3390/life14020254. View

15.

Jadav P, Mohan S, Husain S . Role of deceased donor kidney procurement biopsies in organ allocation. Curr Opin Nephrol Hypertens. 2021; 30(6):571-576. PMC: 8490331. DOI: 10.1097/MNH.0000000000000746. View

16.

de Haan K, Zhang Y, Zuckerman J, Liu T, Sisk A, Diaz M . Deep learning-based transformation of H&E stained tissues into special stains. Nat Commun. 2021; 12(1):4884. PMC: 8361203. DOI: 10.1038/s41467-021-25221-2. View

17.

McMANUS J . The periodic acid routing applied to the kidney. Am J Pathol. 1948; 24(3):643-53. PMC: 1942787. View

18.

Sethi S, DAgati V, Nast C, Fogo A, De Vriese A, Markowitz G . A proposal for standardized grading of chronic changes in native kidney biopsy specimens. Kidney Int. 2017; 91(4):787-789. DOI: 10.1016/j.kint.2017.01.002. View

19.

Racusen L, Solez K, Colvin R, Bonsib S, Castro M, CAVALLO T . The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999; 55(2):713-23. DOI: 10.1046/j.1523-1755.1999.00299.x. View

20.

Antonio Lopes J, Moreso F, Riera L, Carrera M, Ibernon M, Fulladosa X . Evaluation of pre-implantation kidney biopsies: comparison of Banff criteria to a morphometric approach. Kidney Int. 2005; 67(4):1595-600. DOI: 10.1111/j.1523-1755.2005.00241.x. View