Citations 1
Drivers of Diagnostic Variation in a Digital Global Kidney Transplant Reader Study
Hofstraat-Boersma, Rianne, Long, Romy du , Buzzanca, Giorgio , Abiola, Adeyemi A., Albadri, Sam, Ali, Zahabia, Altaleb, Ahmed, Banu, Sultana G., Barry, Marc , Bhalodia, Ami , Bianco, Paola, Broecker, Verena , Buelow, Roman, Cheunsuchon, Boonyarit , Crisi, Giovanna M., Daneshvar, Simin, Dokouhaki, Pouneh, Drachenberg, C., Florquin, Sandrine, Gibson, Ian W., Gujarathi, Saurabh, Hendricks, Allen R. , Islam, Jaynul, Ismail, Wesam, Jagannathan, Geetha , Kläger, Johannes, Krizova, Adriana , Kurien, Anila A., Kwon, Boomi , Ledesma, Felipe L., Martin, Jonne, Mehta, Shweta S., Messias, Nidia , Mignano, Salvatore , Miranda, Monik E., Moeckel, Gilbert, Pala, Chiara, Ranson, Marc A., Rodriguez, A Castell, Rosenberg, Avi, Setty, Suman , Sheaff, M., Soares, Maria F.S., Surintrspanont, Jerasit , Terinte-Balcan, George, Testa, Francesca , Ticas, David O. Hendriquez, Toniolo, Maria F., Midden, Dominique van, Velagapudi, R, Viswanathan, Seethalakshmi , Stillfried, Saskia von, Kalverboer, Nienke , Bruns, Imke B. , Callegaro, Giulia , Vries, A A F De, Peters-Sengers, Hessel, Kers, Jesper, Hofstraat, Rianne , Adefidipe, Adeyemi Abiola, Albadri, Sam , Angioi, Andrea , Banu, Sultana Gulshana, Bianco, Paola, Buelow, Roman David, Chauveau, Bertrand , Chen, Guoli , Crisi, Giovanna Maria, Dendooven, Amélie , Drachenberg, Cinthia Beskow , Farris, Alton B. , Ferlicot, Sophie , Florquin, Sandrine , Fontana, Francesco , Gibier, Jean‐Baptiste , Gibson, Ian W. , Husain, Sufia , Ismail, Wesam, Kläger, Johannes Philipp , Kozakowski, Nicolas , Kurien, Anila Abraham , L’Imperio, Vincenzo , Ledesma, Felipe L , Low, Julia P. , Miranda, Monik Ediana , Price, Brendon , Ranson, Marc Andres, Roelofs, Joris J. T. H. , Sadeghipour, Alireza , Sekulic, Miroslav , Setty, Suman , Soares, Maria Fernanda , Terinte‐Balcan, George , Ticas, David Henriquez, Toniolo, María Fernanda , Midden, Dominique van , Velagapudi, Ramya Krishna , Stillfried, Saskia Freifrau von , Wu, Chih‐Ying , Water, Bob van de , Helm, Danny van der , Sengers, Hessel Peters , Kers, Jesper
No container title available | July 13, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
ABSTRACT Background Diagnostic interpretation of kidney allograft biopsies using the Banff classification remains variable, but the determinants of this variability are not fully defined. We performed a global, fully digital multi-reader study to identify the principal drivers of disagreement in Banff-based assessment. Methods Thirty-six kidney transplant biopsies were independently scored by 67 renal pathologists on a standardized digital platform. Readers assessed Banff lesions on hematoxylin and eosin, periodic acid–Schiff, and Jones’ silver stains; final diagnostic categories were assigned using prespecified Banff-based decision rules. Interobserver agreement was quantified with Gwet’s agreement coefficient (AC) statistics. Determinants of diagnostic agreement were evaluated using pairwise mixed-effects logistic regression, and reader similarity was examined by principal component analysis (PCA) with post hoc molecular annotation. Results Agreement for final diagnostic categories was moderate (Gwet’s AC1, 0.55; 95% CI, 0.47–0.63). Lesion-level agreement varied substantially, with lowest agreement for selected threshold-dependent inflammatory or semi-quantitative lesions, including interstitial inflammation in areas of IFTA, peritubular capillaritis and arteriolar hyalinosis. Diagnostic concordance differed markedly across biopsies, indicating strong case-level heterogeneity. In pairwise models, differences in active inflammatory and vascular lesion scoring were the strongest correlates of diagnostic disagreement; reader experience and geography contributed minimally. Principal component analysis showed reader variation was organized along two dominant axes: a rejection-calling threshold axis linked mainly to tubulointerstitial inflammatory injury, and a T cell-mediated (TCMR/TI) and antibody-mediated/microvascular (AMR/MVI) inflammation-oriented phenotypic classification axis. Conclusion Interobserver variation in Banff-based kidney transplant biopsy assessment is structured rather than random and driven mainly by how readers threshold and integrate key inflammatory lesion compartments rather than experience or geographic location.