Purpose: Microvascular inflammation (MVI) defined by glomerulitis (g) and peritubular capillaritis (ptc) is a hallmark of ABMR in renal transplantation.  The prevalence and significance of MVI in patients without ABMR is less understood.

Methods: Here, we analyzed MVI in the 1st post-transplant year, its relationship to DSA, and its clinical significance in a large cohort of patients without ABMR. Along with any for-cause biopsy (fcBx), patients underwent 2 protocol biopsies (pBx, 3 & 12mos). Bx were categorized as early (0-4mos) or late (5-12mos). Serum was screened for DSA at 0, 1, 3, 6, 9 & 12mos post-transplant.

Results: MVI Prevalence: 956/1187 patients transplanted between 2013-18 underwent 1950 Bx (67% protocol, 33% for-cause). Of these Bx, 64 had either ABMR or GN and were excluded. MVI was noted in 23% (g+ptc score 1-1.5 in 13% & ≥2 in 10%) of the remaining 1887 Bx with greater prevalence in fcBx (fcBx 14% vs. pBx 7%) and late Bx (late Bx 29% vs. early Bx 17%). Of note, the MVI prevalence and its severity increased with increasing grades of tubulointerstitial inflammation (TII) (Fig 1A). Of note, 65% of patients with allograft infections (pyelonephritis & BKVN) had MVI.

MVI & DSA: DSA was detected concurrently in 12% of all the 1887 Bx without ABMR. Although, MVI was associated with concurrent DSA detection in these Bx (OR 1.8, 95% CI 1.3-2.5, p<0.,001), ~60% of the biopsies never had DSA (concurrent/historic or future). Furthermore, in biopsies stratified by the grade of TCMR, there was no significant difference in concurrent DSA detection between patients with and without MVI (Fig.1B).

Outcomes: MVI in patients without ABMR was associated with decreased 7yr-graft survival (Fig 1C, p<0.001). Importantly, the combination of MVI and TII was associated with worse graft survival when compared to either no inflammation or TII alone (Fig1C, p<0.001). Further, in a select sub-group of patients with allograft infection, MVI was associated with a trend towards decreased graft survival compared to no MVI (76% vs. 88%). Finally, MVI was associated with poor graft survival independent of potential confounders including DSA (HR 2.5, 95% CI 1.6-3.4, p<0.001).

Conclusion: MVI is common even in the absence of ABMR or DSA and is a marker for the severity of allograft inflammation and subsequent poor clinical outcomes.