Impact of the Current Versus the Previous Diagnostic Threshold on the Outcome of Patients With Borderline Changes Suspicious for T Cell-mediated Rejection Diagnosed on Indication Biopsies

Transplantation. 2018 Dec;102(12):2120-2125. doi: 10.1097/TP.0000000000002327.

Abstract

Background: Since the borderline changes suspicious for acute T cell-mediated rejection (BL) category was broadened, there has been a debate regarding the right threshold for tubulitis and interstitial inflammation scores.

Methods: We studied a first cohort of 111 patients with BL found on an indication biopsy between 2006 and 2016 and compared those with scores of t1i0 (BLt1i0) to those with higher scores (BL≥t1i1). A second cohort of 56 patients with BL was used for external validation. We used a composite endpoint of death-censored graft failure or doubling of the serum creatinine level postbiopsy.

Results: In the first cohort, 68% (75/111) of the BL cases fell in the BLt1i0 group. At 5 years, the occurrence of the composite endpoint was 5% and 14% for BLt1i0 and BL≥t1i1, respectively. In contrast, the endpoint occurred in 5% of nonrejectors and 21% of patients with T cell-mediated rejection. In the validation cohort, 8% versus 36% of BLt1i0 and BL≥t1i1 reached the endpoint, respectively. Multivariable Cox modeling revealed that BLt1i0 patients had a prognosis similar to that of nonrejectors (adjusted hazard ratio, 0.6; 95% confidence interval, 0.1-2.2; P = 0.40) but better than that of patients with BL≥t1i1 (hazard ratio, 3.8; 95% confidence interval, 1.3-11.5; P = 0.02). Sensitivity analyses restricted to death-censored graft loss or using time posttransplant as the time of reference provided similar results.

Conclusions: In summary, patients with BLt1i0 have a different prognosis to that of BL≥t1i1 patients, which brings into question the current diagnostic thresholds.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biopsy
  • Creatinine / blood
  • Female
  • Graft Rejection / diagnosis*
  • Graft Rejection / immunology
  • Graft Rejection / mortality
  • Graft Rejection / pathology
  • Graft Survival
  • Humans
  • Immunity, Cellular*
  • Kidney / immunology*
  • Kidney / pathology
  • Kidney / surgery*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / mortality
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • T-Lymphocytes / immunology*
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • Creatinine