*Purpose: The Transplant Therapeutics Consortium seeks to translate the iBox from Loupy et al., 2019 into a surrogate endpoint for five-year death-censored graft survival after kidney transplantation. The iBox was derived using: eGFR, proteinuria, kidney allograft biopsy, donor-specific antibody, and time of risk evaluation. A modified version of the iBox Scoring System was developed without biopsy, the abbreviated iBox Scoring System (abbreviated iBox), and measured at one-year post-transplant. The objective of this study was to conduct an external validation to quantify the abbreviated iBox’s discrimination and calibration as a predictor of five-year death censored graft survival.

*Methods: External validation was performed using four datasets (n=1,713): 2 randomized controlled trials (RCTs) (n=872) and 2 observational datasets (n=841), reflective of calcineurin inhibitor (CNI) and CNI-free subjects. The discrimination ability of the abbreviated iBox was assessed using Harrell’s c-statistic. Calibration was assessed using Poisson regression (Crowson et al., 2016).

*Results: The c-statistic values for each validation dataset indicate good predictive ability. The calibration data showed no significant differences in observed versus predicted graft loss events indicating the abbreviated iBox has good calibration. A summary of the external validation results is described below.

*Conclusions: The abbreviated iBox measured at one-year post-transplant was validated in four external datasets as a surrogate for five-year death-censored graft survival. Despite the model being trained on a) primarily CNI subjects, b) measuring the abbreviated iBox at various times post-transplant, and c) inclusion of biopsy in the abbreviated iBox score, the model’s predictive ability is good in both CNI and CNI-free populations, without biopsy data, and with a fixed time one-year post-transplant. The abbreviated iBox may prove to be an important surrogate endpoint for demonstrating superiority of new immunosuppressive therapies in registration-driven clinical trials.

« Back to 2022 American Transplant Congress