Sub-classification of borderline changes into diffuse or focal and its impact on long-term renal transplant outcomes

Borderline changes (BL) with stable renal function is a controversial category in renal transplantation, given its contradictory outcomes. The aim of this study was to compare the clinical outcomes of BL in patients with stable renal function classified as focal and diffuse according to the extent of tubulitis.

Patients with no history of rejection with a surveillance graft biopsy at 3 or 12 months showing BL (n = 40), acute cellular rejection (n = 20) or normal biopsies (n = 20), were included in this study. Biopsies with BL were divided into diffuse BL (BL_D) and focal BL (BL_F) according to the extent of tubulitis. Because of the low frequency of subclinical ACR (ACR_ND) (n = 12), biopsies with ACR and graft dysfunction (ACR_D) (n = 8) were also included. A composite outcome that included the presence of rejection in subsequent biopsies, graft loss, patient death, decrease in GFR ≥30% or presence of de novo DSA (dnDSA) during the first year of follow-up was evaluated.

The primary composite outcome occurred in five patients of each of the Normal, BL_F and ACR_ND, eight patients with BL_D and six patients with ACR_D (p = 0.105). A trend towards more rejection episodes was observed in the ACR_ND and ACR_D. Also, a shorter time to rejection in the BL_D, ACR_ND and ACR_D groups compared to BL_F and Normal groups (p = 0.039) was observed. During the first year of follow-up, no patient in the ACR_ND group developed dnDSA, compared to 15-25% in the other groups. The median time of dnDSA development in the BL_F group was 45 months, and in the BL_D group was 10 months (p = 0.020).

Classifying BL biopsies with stable renal function into focal and diffuse categories, is a simple and feasible strategy that helps to differentiate between BL_D with a phenotype that shows a trend towards worse outcomes, and BL_F that behaves more similar to normal biopsies.