Urinary metabolites predict prolonged duration of delayed graft function in DCDkidney transplant recipients

Autor: Kostidis, S., Bank, J. R., Soonawala, D., Nevedomskaya, E., Kooten, C., Mayboroda, O. A., Fijter, J. W.
Zdroj: American Journal of Transplantation; January 2019, Vol. 19 Issue: 1 p110-122, 13p
Abstrakt: Extending kidney donor criteria, including donation after circulatory death (DCD), has resulted in increased rates of delayed graft function (DGF) and primary nonfunction. Here, we used Nuclear Magnetic Resonance (NMR) spectroscopy to analyze the urinary metabolome of DCDtransplant recipients at multiple time points (days 10, 42, 180, and 360 after transplantation). The aim was to identify markers that predict prolonged duration of functional DGF(fDGF). Forty‐seven metabolites were quantified and their levels were evaluated in relation to fDGF. Samples obtained at day 10 had a different profile than samples obtained at the other time points. Furthermore, at day 10 there was a statistically significant increase in eight metabolites and a decrease in six metabolites in the group with fDGF(N = 53) vis‐à‐vis the group without fDGF(N = 22). In those with prolonged fDGF(≥21 days) (N = 17) urine lactate was significantly higher and pyroglutamate lower than in those with limited fDGF(<21 days) (N = 36). In order to further distinguish prolonged fDGFfrom limited fDGF, the ratios of all metabolites were analyzed. In a logistic regression analysis, the sum of branched‐chain amino acids (BCAAs) over pyroglutamate and lactate over fumarate, predicted prolonged fDGFwith an AUCof 0.85. In conclusion, kidney transplant recipients with fDGFcan be identified based on their altered urinary metabolome. Furthermore, two ratios of urinary metabolites, lactate/fumarate and BCAAs/pyroglutamate, adequately predict prolonged duration of fDGF. Day 10 urinary ratios of branch‐chain amino acids over pyroglutamate and lactate over fumarate, measured by routine high‐throughput nuclear magnetic resonance spectroscopy, correlate with prolonged duration of delayed graft function (beyond 21 days) in donation after circulatory death kidney transplant recipients.
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