The clinical significance of early histological BBC in kidney transplant recipients (KTR) is unclear. It is also unknown if biomarkers predict progression to acute rejection vs. spontaneously regression. 154/372 KTRs (3mo & 1yr protocol Bx) transplanted between dates 1/13-11/14 with BBC (27%; 42/154) vs. normal (NL) histology (73%; 112/154) were prospectively analysed for progression by 1yr. In comparison to NL, KTR with BBC at 3mo had similar rates of BBC at 1yr (36% vs. 28%), but markedly increased progression to TCMR≥Banff1A (41%vs.14%, p=0.0001). Conversely, more KTR with NL at 3mo were NL at 1yr compared to those with 3mo BBC (58% vs. 23%, p=0.001). Further, KTR with 3mo BBC have significantly higher creatinine at 24mo (1.73 vs.1.49, p=0.04) and chronicity scores at 1yr (2.9 vs.2.2, p=0.006), compared to those with NL. Importantly, in KTRs with 3mo BBC, those with persistent BBC/progression (TCMR) at 1yr had significantly worse chronicity scores (ct+cv+ci) at 1yr (3.21 vs. 1.45, p=0.0002), IF+i positivity (78% vs. 0%, p<0.0001) and renal dysfunction at 2yrs (creatinine: 1.9 vs.1.28, p=0.02), compared to those whose inflammation resolved. Thus, in KTR with 3mo BBC, persistence/progression of inflammation at 1yr increases risk for adverse graft outcomes. Clinical factors (e.g. DGF, de novo DSA, sCr, & histology at 3mo) could not predict progression/persistence vs. resolution. Based on our finding that B cell cytokine expression profiles (after CD40L/CpG stimulation) predict rejection, we asked if IL-10:TNFa expression ratio within transitional B cells (TrB) could predict progression/persistence vs. resolution of 3mo BBC. PBMCs were available for 28/42 KTR with 3mo BBC. Of these 28, 10 resolved, and 18 persisted/progressed by 1yr. IL-10:TNFa ratio in TrBs (0.73 vs. 2.46, p=0.02) and in the most immature “T1” TrB cells (1.42 vs. 4.84, p=0.01) were significantly reduced in patients with persistence/progression vs. resolution, indicating a more pro-inflammatory cytokine profile. Importantly, the T1 IL-10/TNFa ratio strongly predicted progression/persistence in KTR with 3mo BBC (AUC 0.875; p=0.001; sensitivity 93% specificity 80%).

Conclusion: KTR with early BBC that exhibit either progressive/persistent tubulointerstitial inflammation at 1yr represent a high-risk cohort for graft dysfunction. This group might be predicted early by the T1 B cell IL-10:TNFa ratio at 3mo. This finding and its clinical utility must now be validated in a bigger cohort.

CITATION INFORMATION: Cherukuri A, Sharma A, Mehta R, Hariharan S, Rothstein D. Persistence/Progression of Early Banff Borderline Changes (BBC) Is Associated with Chronic Renal Allograft Damage and Can Be Predicted by B Cell Cytokine Profile. Am J Transplant. 2017;17 (suppl 3).

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