Evaluation of a Pre-Transplant Serum FTIR Rejection-Risk Score Across Time Horizons and Rejection Phenotype-Defined Endpoints in Kidney Transplantation

Background: Pre-transplant serum Fourier-transform infrared spectroscopy (FTIRS) has identified an internally validated biochemical signal associated with subsequent biopsy-proven kidney allograft rejection. Whether this signal retains discrimination across post-transplant time horizons and rejection-phenotype-defined endpoints remains unclear. Methods: This internally conducted extension study reused the same single-center cohort of 79 kidney transplant recipients (40 with biopsy-proven rejection; 39 with five-year rejection-free follow-up). The primary analysis did not retrain the original model; the fixed nested out-of-fold FTIR-derived score was evaluated at cumulative rejection horizons of 30, 90, 180, 365, 730, 1095, and 1825 days. Discrimination was assessed using AUCs with bootstrap confidence intervals and permutation testing. Cox regression, C-index, Kaplan–Meier analysis, exploratory decision curve analysis, and exploratory endpoint-specific models were also performed. Results: The fixed score retained discrimination across horizons, with AUCs of 0.780, 0.829, 0.845, and 0.860 at 30, 90, 180, and 365 days, respectively, and 0.850 at 1825 days. In Cox analysis, the FTIRS score was associated with rejection risk (HR per SD 1.95, 95% CI 1.40–2.73; p = 0.00009; C-index 0.709). Endpoint-specific models showed variable discrimination but involved small subgroups. Conclusions: The fixed pre-transplant FTIRS score retained discriminatory value across cumulative rejection-time horizons, with numerically highest discrimination within the first year. Endpoint-specific findings were hypothesis-generating and did not establish time- or phenotype-specific spectral signatures. Independent external validation is required.