Mitochondrial membrane potential and delayed graft function following kidney transplantation

Abstract

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 = _1.08 1.38_1.78 , 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.

Keywords: basic (laboratory) research/science; cytotoxicity; donors and donation: deceased; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; translational research/science.

Figure 1.. Pre-transplant MMP levels by post-transplant day 5 graft function groups.

Patients were classified as having delayed graft function (DGF; required post-transplant dialysis during hospitalization), slow graft function (SGF; serum creatinine >3.0 mg/dL), or immediate graft function (serum creatinine ≤3.0 mg/dL). Patients with DGF had significantly lower MMP levels than patients with SGF or IGF (overall Kruskal-Wallis test p=0.003).