TY - JOUR
T1 - Mitochondrial membrane potential and delayed graft function following kidney transplantation
AU - Garonzik-Wang, Jacqueline M.
AU - Lonze, Bonnie E.
AU - Ruck, Jessica M.
AU - Luo, Xun
AU - Massie, Allan B.
AU - Melancon, Keith
AU - Burdick, James F.
AU - Segev, Dorry L.
AU - Sun, Zhaoli
N1 - Publisher Copyright:
© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2019/2
Y1 - 2019/2
N2 - Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P =.002) and donation after cardiac death donors (75% vs 12%, P =.004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.081.381.78, P =.01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.
AB - Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P =.002) and donation after cardiac death donors (75% vs 12%, P =.004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.081.381.78, P =.01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.
KW - basic (laboratory) research/science
KW - cytotoxicity
KW - donors and donation: deceased
KW - kidney (allograft) function/dysfunction
KW - kidney transplantation/nephrology
KW - translational research/science
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U2 - 10.1111/ajt.15174
DO - 10.1111/ajt.15174
M3 - Article
C2 - 30408329
AN - SCOPUS:85057968573
SN - 1600-6135
VL - 19
SP - 585
EP - 590
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 2
ER -