Are borderline changes real rejection? Current viewpoints.

Abstract

The clinical significance and treatment of borderline changes are controversial. The lowest detectable margin for rejection on histology is unclear. We review recent evidence about borderline changes and related biomarkers. Borderline change (Banff ≥ t1i1) is associated with progressive fibrosis, a greater propensity to form de-novo DSA, and reduced graft survival. Isolated tubulitis appears to have similar kidney allograft outcomes with normal controls, but this finding should be validated in a larger, diverse population. When borderline change was treated, a higher chance of kidney function recovery and better clinical outcomes were observed. However, spontaneous borderline changes resolution without treatment was also observed. Various noninvasive diagnostic biomarkers have been developed to diagnose subclinical acute rejection, including borderline changes and ≥ Banff 1A TCMR. Biomarkers using gene expression and donor-derived cell-free DNA, and HLA DR/DQ eplet mismatch show potential to diagnose subclinical acute rejection (borderline change and ≥Banff 1A TCMR), to avoid surveillance biopsy, or to predict poor kidney allograft outcomes. Borderline changes are associated with poor kidney allograft outcomes, but it remains unclear if all cases of borderline changes should be treated. Novel biomarkers may inform physicians to aid in the diagnosis and treatment.