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 - Funding Information:
This work was supported by grant numbers K23DK115908 and K24DK101828 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The third author (JR) is supported by a Doris Duke Clinical Research Foundation grant.
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 -