Subclinical and Borderline Rejection are Associated With Death‐Censored Graft Loss After Kidney Transplantation: A Systematic Review and Meta‐Analysis

BACKGROUND: The prognostic significance of subclinical rejection (SCR) and borderline rejection (BLR) detected on surveillance kidney allograft biopsies remains uncertain. METHODS: We performed a systematic review and meta-analysis of studies enrolling adult kidney transplant (KT) recipients undergoing protocol biopsies. The primary outcome was death-censored graft loss (DCGL); the secondary outcome was subsequent rejection. Random-effects models, sensitivity analyses, and meta-regression were used. RESULTS: Fifteen studies (5428 recipients) were included. SCR was associated with a higher risk of DCGL (RR 2.22; 95% CI 1.67-2.95) and subsequent rejection (RR 3.09; 95% CI 2.34-4.09), with low heterogeneity. Both T cell-mediated rejection (RR 1.82; 95% CI 1.28-2.61) and antibody-mediated rejection (ABMR) (RR 3.35; 95% CI 2.11-5.33) were associated with increased DCGL. BLR was associated with increased DCGL (RR 2.40; 95% CI 1.67-3.46) and subsequent rejection (RR 2.79; 95% CI 2.10-3.69). Findings were robust across sensitivity analyses, including contemporary Banff-era definitions. CONCLUSIONS: SCR and BLR are associated with inferior long-term graft outcomes. These findings underscore their prognostic significance and warrant prospective studies to determine optimal management strategies.