Data Sheet 1_Prognostic impact of rejection and chronicity index on long-term graft outcomes in pediatric kidney transplant recipients.docx

BackgroundAcute rejection remains a major complication in pediatric kidney transplantation. The Banff Activity Index (AI) and Chronicity Index (CI) have recently been proposed as quantitative composites of histological lesions that represent the extent of active and chronic injury, respectively. Emerging evidence suggests that these indices provide additional value for prognostic assessment. However, their clinical significance in pediatric recipients remains unclear.
MethodsThis single-center retrospective study included 535 pediatric kidney transplant recipients who underwent transplantation between 2015 and 2025. AI and CI were calculated according to Banff lesion scores. Logistic regression was used to identify risk factors for rejection, and graft functional outcomes were evaluated using Kaplan–Meier analysis and longitudinal estimated glomerular filtration rate (eGFR) trajectories across rejection phenotypes and AI/CI categories.
ResultsAmong 535 recipients, 98 (18.3%) experienced 126 rejection episodes. Independent risk factors for rejection included HLA-DR mismatch (OR 1.60, 95% CI 1.09–2.43, p = 0.021), previous transplantation (OR 3.05, 95% CI 1.03–8.53, p = 0.036), preformed donor-specific antibodies (pfDSA) (OR 3.11, 95% CI 1.08–8.31, p = 0.027), and recipient aged 9–15 years (OR 2.05, 95% CI 1.30–3.29, p = 0.002). Both AI and CI scores varied significantly across rejection phenotypes, with mixed rejection showing the highest levels of histological activity and chronicity (AI: p < 0.001; CI: p = 0.017). Higher AI scores were associated with a stepwise decline in eGFR at diagnosis (p = 0.001), but this difference was no longer significant during long-term follow-up. In contrast, high CI (≥ 4) was linked to lower eGFR at 3 years post-rejection compared with low CI (< 4) (35.9 vs. 62.8 mL/min/1.73 m²; p = 0.016). High CI (≥ 4) at the first biopsy was independently associated with donation after circulatory death (DCD) (OR 3.95, p = 0.04) and biopsy performed ≥ 3 years post-transplantation (OR 3.80, p = 0.05).
ConclusionAcute rejection remains significantly associated with adverse long-term graft outcomes in pediatric kidney transplantation. CI ≥ 4 was associated with long-term functional decline, whereas AI primarily reflected short-term functional impairment.