TY - JOUR
T1 - Comparing the prognostic performance of iBOX and biopsy-proven acute rejection for long-term kidney graft survival
AU - Transplant Therapeutics Consortium
AU - Klein, Amanda
AU - Kosinski, Luke
AU - Loupy, Alexandre
AU - Frey, Eric
AU - Stegall, Mark
AU - Helanterä, Ilkka
AU - Newell, Kenneth
AU - Meier-Kriesche, Herwig Ulf
AU - Mannon, Roslyn B.
AU - Fitzsimmons, William E.
N1 - Publisher Copyright:
© 2024 American Society of Transplantation & American Society of Transplant Surgeons
PY - 2024/10
Y1 - 2024/10
N2 - Biopsy-proven acute rejection (BPAR) occurs in approximately 10% of kidney transplant recipients in the first year, making superiority trials unfeasible. iBOX, a quantitative composite of estimated glomerular filtration rate, proteinuria, antihuman leukocyte antigen donor-specific antibody, and + full/− abbreviated kidney histopathology, is a new proposed surrogate endpoint. BPAR's prognostic ability was compared with iBOX in a pooled cohort of 1534 kidney transplant recipients from 4 data sets, including 2 prospective randomized controlled trials. Discrimination analyses showed mean c-statistic differences between both iBOX compared with BPAR of 0.25 (95% confidence interval: 0.17-0.32) for full iBOX and 0.24 (95% confidence interval: 0.16-0.32) for abbreviated iBOX, indicating statistically significantly higher c-statistic values for the iBOX prognosis of death-censored graft survival. Mean (± standard error) c-statistics were 0.81 ± 0.03 for full iBOX, 0.80 ± 0.03 for abbreviated iBOX, and 0.57 ± 0.03 for BPAR. In calibration analyses, predicted graft loss events from both iBOX models were not significantly different from those observed. However, for BPAR, the predicted events were significantly (P <.01) different (observed: 64; predicted: 70; full iBOX: 76; abbreviated iBOX: 173 BPAR). IBOX at 1-year posttransplant is superior to BPAR in the first year posttransplant in graft loss prognostic performance, providing valuable additional information and facilitating the demonstration of superiority of novel immunosuppressive regimens.
AB - Biopsy-proven acute rejection (BPAR) occurs in approximately 10% of kidney transplant recipients in the first year, making superiority trials unfeasible. iBOX, a quantitative composite of estimated glomerular filtration rate, proteinuria, antihuman leukocyte antigen donor-specific antibody, and + full/− abbreviated kidney histopathology, is a new proposed surrogate endpoint. BPAR's prognostic ability was compared with iBOX in a pooled cohort of 1534 kidney transplant recipients from 4 data sets, including 2 prospective randomized controlled trials. Discrimination analyses showed mean c-statistic differences between both iBOX compared with BPAR of 0.25 (95% confidence interval: 0.17-0.32) for full iBOX and 0.24 (95% confidence interval: 0.16-0.32) for abbreviated iBOX, indicating statistically significantly higher c-statistic values for the iBOX prognosis of death-censored graft survival. Mean (± standard error) c-statistics were 0.81 ± 0.03 for full iBOX, 0.80 ± 0.03 for abbreviated iBOX, and 0.57 ± 0.03 for BPAR. In calibration analyses, predicted graft loss events from both iBOX models were not significantly different from those observed. However, for BPAR, the predicted events were significantly (P <.01) different (observed: 64; predicted: 70; full iBOX: 76; abbreviated iBOX: 173 BPAR). IBOX at 1-year posttransplant is superior to BPAR in the first year posttransplant in graft loss prognostic performance, providing valuable additional information and facilitating the demonstration of superiority of novel immunosuppressive regimens.
KW - BPAR
KW - clinical trials
KW - data sharing
KW - drug development
KW - efficacy failure endpoint
KW - iBOX
KW - immunosuppressive therapies
KW - kidney transplantation
KW - performance
KW - prognostic
KW - public-private-partnership
KW - qualification
KW - TCMR grade 1a or greater
KW - 3126 Surgery, anesthesiology, intensive care, radiology
U2 - 10.1016/j.ajt.2024.04.004
DO - 10.1016/j.ajt.2024.04.004
M3 - Article
C2 - 38642711
AN - SCOPUS:85192157420
SN - 1600-6135
VL - 24
SP - 1784
EP - 1793
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 10
ER -