Three-month course of intragraft transcriptional changes in kidney allografts with early histological minimal injury - a cohort study

The tubulitis with/without interstitial inflammation not meeting criteria for T-cell-mediated rejection (minimal allograft injury) is the most frequent histological findings in early transplant biopsies. The course of transcriptional changes in sequential kidney graft biopsies has not been studied yet. Molecular phenotypes were analyzed using the Molecular Microscope(R) Diagnostic System (MMDx) in 46 indication biopsies (median 13 postoperative days) diagnosed as minimal allograft injury and in corresponding follow-up biopsies at 3 months. All 46 patients with minimal injury in early biopsy received steroid pulses. MMDx interpreted indication biopsies as no-rejection in 34/46 (74%), T-cell-mediated rejection (TCMR) in 4/46 (9%), antibody-mediated rejection in 6/46 (13%), and mixed rejection in 2/46 (4%) cases. Follow-up biopsies were interpreted by MMDx in 37/46 (80%) cases as no-rejection, in 4/46 (9%) as TCMR, and in 5/46 (11%) as mixed rejection. Follow-up biopsies showed a decrease in MMDx-assessed acute kidney injury (P = 0.001) and an increase of atrophy-fibrosis (P = 0.002). The most significant predictor of MMDx rejection scores in follow-up biopsies was the tubulitis classifier score in initial biopsies (AUC = 0.84, P = 0.002), confirmed in multivariate binary regression (OR = 16, P = 0.016). Molecular tubulitis score at initial biopsy has the potential to discriminate patients at risk for molecular rejection score at follow-up biopsy.

Automated summary

Tubulitis with/without interstitial inflammation not meeting criteria for T-cell-mediated rejection is the most common histological finding in early transplant biopsies, and the course of transcriptional changes in sequential kidney graft biopsies has not been studied yet. Through molecular phenotyping using MMDx, it was found that the tubulitis classifier score at initial biopsy is the most significant predictor of rejection scores in follow-up biopsies, able to discriminate patients at risk for rejection.