Renal allograft microcirculation inflammation (MI) lesions including glomerulitis (g) and peritubular capillaritis (ptc) are associated with AMR and poor outcomes. The significance of MI lesions detected in the early post-transplant period in patients without AMR is unknown. In this prospective study, we examined MI lesions in the early post-transplant period and their association with TCMR.

Subjects: 294/372 KTRs had serial biopsies (for-cause & protocol:3&12mo) and DSA assessment through the first year. 36.7% (N=108) patients in this study experienced TCMR (17.3% clinical (ACR) & 18.4% sub-clinical (SCR)) in the first year. 3.7% of the patients (n=11) had concomitant AMR.

MI lesions: Of the 294 KTRs, 27.6% (n=81) had detectable MI lesions in the 1^st year. Whilst 31 KTRs (10.5%) had 'g' lesions and 18 (6.1%) had 'ptc' lesions alone, 32 (11%) KTRs had both 'g' and 'ptc' lesions. Further, 39.5%of these 81 KTRs, had 'g+ptc' score≥2.

MI lesions and TCMR: 14.7% of patients with no TCMR, 19.7% with Borderline changes, 40.3% with Banff 1A and 54% with Banff ≥1B had MI lesions (p<0.0001). Even after excluding AMR, 46.2% of KTRs with isolated TCMR had these lesions. Importantly, 38% of the patients with SCR had these lesions in comparison to 16% with no rejection and 55% with ACR (p<0.0001).

MI lesions & Outcomes: MI lesions were associated with significantly worse IFTA (p-=0.004) and increased graft loss or impending graft loss (eGFR<30ml/min & >30% decline from baseline) (Fig 1A, 1B). Importantly, in combination with TCMR, these lesions were associated with the worst IFTA scores (p<0.001) and graft outcome (Fig1C). Thus patients with MI+TCMR represent a very high risk group for poor graft outcomes.

Risk factors for MI+TCMR: In a multivariate logistic regression model, post-transplant DSA (OR 2.7, p=0.02) and non-adherence (OR 3.3, p=0.001) defined by high CNI intra-patient variability (>35%) were independently associated with MI+TCMR

Conclusions: Thus, we show that MI lesions are associated with isolated TCMR. Furthermore, post-transplant DSA and non-adherence are risk factors for the development of MI+TCMR, a phenotype associated with poor graft outcomes.

CITATION INFORMATION: Cherukuri A., Chittka D., Mehta R., Sharma A., Sood P., Hariharan S. Early Microcirculation Inflammation Associated with TCMR Leads to Poor Graft Outcomes in Kidney Transplant Recipients (KTRs) Am J Transplant. 2017;17 (suppl 3).

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