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Scoring Total Inflammation Is Superior to the Current Banff Inflammation Score in Predicting Outcome and the Degree of Molecular Disturbance in Renal Allografts

2009; Elsevier BV; Volume: 9; Issue: 8 Linguagem: Inglês

10.1111/j.1600-6143.2009.02727.x

1600-6143

Michael Mengel, J. Reeve, Sakarn Bunnag, Gunilla Einecke, Gian S. Jhangri, B. Sis, Konrad S. Famulski, L. Guembes-Hidalgo, Philip F. Halloran,

Transplantation: Methods and Outcomes

Emerging molecular analysis can be used as an objective and independent assessment of histopathological scoring systems. We compared the existing Banff i-score to the total inflammation (total i-) score for assessing the molecular phenotype in 129 renal allograft biopsies for cause. The total i-score showed stronger correlations with microarray-based gene sets representing major biological processes during allograft rejection. Receiver operating characteristic curves showed that total-i was superior (areas under the curves 0.85 vs. 0.73 for Banff i-score, p = 0.012) at assessing an abnormal cytotoxic T-cell burden, because it identified molecular disturbances in biopsies with advanced scarring. The total-i score was also a better predictor of graft survival than the Banff i-score and essentially all current diagnostic Banff categories. The exception was antibody-mediated rejection which is able to predict graft loss with greater specificity (96%) but at low sensitivity (38%) due to the fact that it only applies to cases with this diagnosis. The total i-score is able to achieve moderate sensitivities (60–80%) with losses in specificity (60–80%) across the whole population. Thus, the total i-score is superior to the current Banff i-score and most diagnostic Banff categories in predicting outcome and assessing the molecular phenotype of renal allografts. Emerging molecular analysis can be used as an objective and independent assessment of histopathological scoring systems. We compared the existing Banff i-score to the total inflammation (total i-) score for assessing the molecular phenotype in 129 renal allograft biopsies for cause. The total i-score showed stronger correlations with microarray-based gene sets representing major biological processes during allograft rejection. Receiver operating characteristic curves showed that total-i was superior (areas under the curves 0.85 vs. 0.73 for Banff i-score, p = 0.012) at assessing an abnormal cytotoxic T-cell burden, because it identified molecular disturbances in biopsies with advanced scarring. The total-i score was also a better predictor of graft survival than the Banff i-score and essentially all current diagnostic Banff categories. The exception was antibody-mediated rejection which is able to predict graft loss with greater specificity (96%) but at low sensitivity (38%) due to the fact that it only applies to cases with this diagnosis. The total i-score is able to achieve moderate sensitivities (60–80%) with losses in specificity (60–80%) across the whole population. Thus, the total i-score is superior to the current Banff i-score and most diagnostic Banff categories in predicting outcome and assessing the molecular phenotype of renal allografts.