Abstract: SA-PO467

An Integrative Approach of Assessing Peritubular Capillaritis Extent and Score in Microvascular Inflammation Is Superior in Predicting Transplant Glomerulopathy and Graft Loss

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Kikic, Zeljko, Medical University Vienna, Vienna, Austria
  • Eskandary, Farsad Alexander, Medical University Vienna, Vienna, Austria
  • Bond, Gregor, None, Vienna, w, Austria
  • Bohmig, Georg, Medical University Vienna, Vienna, Austria
  • Kozakowski, Nicolas, Medical University Vienna, Vienna, Austria
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 1diffuse, n=25) and no glomerulitis were added as a surrogate of antigen-antibody interaction. Outcomes measured were prediction 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 1diffuse in addition to the MVI score≥2 significantly increased the receiver operating characteristic curve for TG [AUC: 0.605 (95%CI 0.53-0.68), p=0.003] compared to the Banff MVI score ≥2 [AUC: 0.571 (95%CI 0.49-0.64), p=0.046] or C4d + [AUC: 0.540 (95%CI 0.47-0.61), p=0.26]. After adjusting for multiple confounders, including C4d or cellular rejection, ptc 1diffuse remained independently related to TG [OR 2.13 (CI: 1.22-3.72), p=0.008]. Ptc 1diffuse and MVI score ≥2 subjects had similar graft survival (44%) compared to patients with ptc 1 focal or without MVI with best overall survival ( 70% and 68%) after a mean follow-up of 9 years.

Conclusion

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