Introduction: In experimental liver transplantation (LTx), glycine, a non-essential amino acid, has been shown to prevent the activation of Kupffer cells and to reduce ischemia/reperfusion injury (IRI) in the liver. Material and Methods: A randomized controlled double-blinded clinical trial with two parallel study arms was performed. A total of 130 patients undergoing primary whole-liver transplantation were randomized and received 250 ml of either 4.4 % glycine solution (n=66) or injectable water (n=64) intravenously (i.v.) during the anhepatic phase and once a day during the first 7 consecutive postoperative days. Primary endpoints were peak levels of aspartate-amino-transaminase (AST)/alanine-aminotransaminase (ALT) as surrogates for the progression of liver related IRI, as well as graft and patient survival. Furthermore, the effect of glycine on cyclosporine A-induced nephrotoxicity is evaluated. Results: The intention to treat analysis as well as the per protocol analysis showed no difference in primary or secondary endpoints between the two study arms. A post-hoc subgroup analysis comparing patients with very high plasma glycine concentrations during the anhepatic phase of LTx (≥7000 ng/ml, n=29) and those with lower concentrations (<7000 ng/ml; n=68) was performed. A relative but not statistically significant reduction of ALT levels during the first 24 hrs and on the first day after LTx, as well as an improvement of patients' overall survival was related with higher plasma glycine levels. Comparison of the post-reperfusion biopsy results showed a significant reduction in both mild and moderate IRI in patients with very high plasma glycine concentrations. Glycine improved eGFR, not only in patients within the target Cyclosporine trough levels, but also in patients with trough levels much higher than target. Conclusion: Although the per protocol analysis could not verify the hypothesized effects of glycine, very high plasma concentrations of glycine achieved at the anhepatic phase proved to be safe, hepatoprotective and nephroprotective.

CITATION INFORMATION: Nickkholgh A, Schemmer P, Polychronidis G, Luntz S, Mayatepek E, Büchler M, Klar E. Glycine Is Graft Protective and Improves Kidney Function After Liver Transplantation: Data from HEGPOL-Trial. Am J Transplant. 2016;16 (suppl 3).

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