Inflammation in fibrotic renal parenchyma (i-IFTA) is associated with decreased graft survival but by Banff rules is not diagnostic for rejection. Some researchers believe that i-IFTA represents chronic active T cell-mediated rejection (TCMR). The alternative view is that i-IFTA represents a response to wounding caused by continuing nephron injury. We analyzed our indication biopsies that had been scored for i-IFTA to determine the frequency of histologic or molecular TCMR and its role in i-IFTA.

One pathologist scored i-IFTA in 234 biopsies, blinded to molecular results. Using our Molecular Microscope® diagnostic system (MMDx), based on the gene expression, we conducted the archetypal analysis (a meta-classifier based on seven molecular classifiers) and assigned biopsies to three molecular diagnoses: antibody-mediated rejection (ABMR), TCMR and no rejection. We also assigned molecular scores of kidney injury (AKI) and T cell burden (QCAT).

We compared biopsies with iIFTA to those with no i-IFTA. The i-IFTA biopsies had a higher frequency of histologic ABMR (31%) and by MMDx (37%) but not TCMR (histology 8%; MMDx 6%). Manyi-IFTA biopsies did not have rejection by histology (53%) or MMDx (54%).

As expected, graft failures were also higher in i-IFTA biopsies (46% vs. 17%, Figure 1), mainly due to ABMR (by MMDx n=24) but not TCMR (by MMDx n=5).

i-IFTA biopsies had increased molecular injury (AKI) and T cell burden (QCAT) scores, the latter compatible with the inflammation. I-IFTA biopsies also had higher molecular classifier scores for ABMR but not TCMR. TCMR classifier scores in i-IFTA>0 biopsies were below 0.10 cut off for positivity.

We conclude that i-IFTA is a reflection of inflammation triggered by the response to wounding and is seldom associated with TCMR (confirming the Banff criteria). The injury triggering i-IFTA should be identified if possible, e.g. ongoing ABMR, recurrent disease, recent successfully treated TCMR. Prognosis is worse for kidneys with i-IFTA because they are experiencing some process inducing parenchymal injury, and the inflammation in scarred areas reflects the response to wounding and not active TCMR.

CITATION INFORMATION: Halloran P., Chang J., Famulski K. Inflammation in Scarred Areas (I-IFTA) is a Reflection of Parenchymal Injury (Response to Wounding) Not T Cell-Mediated Rejection Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress