Background:

Banff Classification accepts two histomorphological features as surrogates of HLA Antibody-Antigen interaction on renal endothelium: C4d staining and microvascular inflammation scores (MVI sum score:ptc+g≥2) which are strong predictors of transplant glomerulopathy (TG) and subsequent graft loss. However, increasing evidence questions the ability of the ptc score to solely mirror all diagnostic and prognostic aspects of ptc morphology. More recently we observed a highly significant relationship of diffuse extent of ptc (inflammation of >50% the renal cortex) with graft loss and significantly higher DSA levels suggesting potential inclusion of diffuse ptc as an additional surrogate of antibody-antigen interaction.

Methods:

We included 616 patients (Tx 1999-2006) with adequate material for interpretation of MVI and C4d staining in first indication biopsies. Alternatively we assessed MVI with an integrated view of ptc morphology including both results of ptc score and ptc extent: additionally to MVI scores, cases with a ptc score of 1 but diffuse extent of ptc (ptc 1_diffuse, n=26) and no glomerulitis were added as a surrogate of antigen-antibody interaction. Outcomes measured were presence of any TG in all indication biopsies (n=1619) and death-censored graft loss until 01.01.2017.

Results:

Linear C4d in PTCs and MVI scores ≥2 were observed in 11% and 19% of the specimens. TG (cg score>0) in one or more biopsies was found in 13% of patients. The incorporation of ptc 1_diffuse in addition to the MVI score≥2 significantly increased the ROC for TG [AUC 0.613 (95%CI 0.54-0.69), p=0.002] compared to the current MVI score ≥2 [AUC 0.571 (95%CI 0.49-0.64), p=0.046] or linear C4d in PTCs [AUC 0.540 (95%CI 0.47-0.61), p=0.26]. After adjusting for multiple confounders, including C4d or cellular rejection, ptc 1_diffuse remained independently related to TG [OR 3.88 (CI: 1.42-10.57), p=0.008].Patients with ptc1_diffuse had worse graft survival than with MVI score ≥2 or <2 (42 vs. 59 vs. 70%, p=0.002).

Conclusion:

An integrated view of ptc morphology including diffuse ptc in assessing MVI is superior for TG and subsequent graft loss risk prediction.

CITATION INFORMATION: Kozakowski N., Herkner H., Eskandary F., Eder M., Winnicki W., Bond G., Kikić Ž. An Integrative Approach for the Assessment of Peritubular Capillaritis Extent and Score in Microvascular Inflammation – Association with Transplant Glomerulopathy and Graft Loss Am J Transplant. 2017;17 (suppl 3).

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