Advances in Clinical and Experimental Medicine
2014, vol. 23, nr 6, November-December, p. 947–952
Publication type: original article
Gamma-Glutamyl Transpeptidase as the Marker of Kidney Graft Function
1 Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland
2 Department of Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
3 Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
4 Department of Pharmacology, Pomeranian Medical University, Szczecin, Poland
5 Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland
Background. Gamma-glutamyl transpeptidase (GGT) is a glycoprotein of the external surface of various cell types. The activity of GGT has been observed in cells and tissues with secretory activity, such as the proximal tubular cells in kidneys. GGT also plays an important pro-oxidant role, stimulating the generation of hydroxyl radicals, and increases membrane lipid peroxidation.
Objectives. In this study we examined whether the monitoring of GGT activity in urine may be a prognostic factor of kidney allograft function. The study enrolled 107 Caucasian renal transplant recipients.
Material and Methods. Urine samples were collected for GGT and creatinine analysis on the 1st day after transplantation, and then in the 3rd and 12th month.
Results. Higher urine GGT activity in the 3rd month after transplantation was associated with significantly higher risk of graft failure (HR = 1.063 per each U/g creatinine; 95%Cl:1.004-1.127; p = 0.037) in the Cox proportional hazards model. Moreover, there were positive correlations between urine GGT and the grade of interstitial fibrosis (Rs = 0.64, p = 0.01) and tubular atrophy (Rs = 0.54, p = 0.056) in specimens collected in the 3rd month after transplantation.
Conclusion. Our results suggest that higher urine GGT activity in the 3rd month after transplantation may be a prognostic factor of graft failure.
gamma-glutamyl transpeptidase, kidney, graft.
- Han L, Hiratake J, Tachi N, Suzuki H, Kumagai H, Sakata K: Gamma-(monophenyl)phosphono glutamate analogues as mechanism-based inhibitors of gamma-glutamyl transpeptidase. Bioorg Med Chem 2006, 14, 6043–6054.
- Wickham S, Regan N, West MB, Thai J, Cook PF, Terzyan SS, Li PK, Hanigan MH: Inhibition of human g-glutamyl transpeptidase: development of more potent, psychologically relevant, uncompetitive inhibitors. Biochem J 2013, 450, 547–557.
- Conigrave KM, Degenhardt LJ, Whitfield JB, Saunders JB, Helander A, Tabakoff B: CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project. Alcohol Clin Exp Res 2002, 26, 332–339.
- Ceyssens B, Pauwels M, Meulemans B, Verbeelen D, Van den Branden C: Increased oxidative stress in the mouse adriamycin model of glomerulosclerosis is accompanied by deposition of ferric iron and altered GGT activity in renal cortex. Ren Fail 2004, 26, 21–27.
- Corti A, Paolicchi A, Franzini M, Dominici S, Casini AF, Pompella A: The S-thiolating activity of membrane gamma-glutamyltransferase: formation of cysteinyl-glycine mixed disulfides with cellular proteins and in the cell microenvironment. Antioxid Redox Signal 2005, 7, 911–918.
- Paolicchi A, Dominici S, Pieri L, Maellaro E, Pompella A: Glutathione catabolism as a signaling mechanism. Biochem Pharmacol 2002, 64, 1027–1035.
- Donadio C, Tramonti G, Lucchesi A, Giordani R, Lucchetti A, Bianchi C: Gamma-glutamyltransferase is a reliable marker for tubular effects of contrast media. Ren Fail 1998, 20, 319–324.
- Tate SS, Meister A: Gamma-glutamyl transpeptidase from kidney. Methods Enzymol 1985, 113, 400–419.
- Karp DR, Shimooku K, Lipsky PE: Expression of gamma-glutamyl transpeptidase protects Ramos B cells from oxidation-induced cell death. J Biol Chem 2001, 276, 3798–3804.
- Elfarra AA, Anders MW: Renal processing of glutathione conjugates, role in nephrotoxicity. Biochem Pharmacol 1984, 33, 3729–3732.
- Dekant W: Bioactivation of nephrotoxins and renal carcinogens by glutathione S-conjugate formation. Toxicol Lett 1993, 67, 151–160.
- Marathe GV, Nash B, Haschemeyer RH, Tate SS: Ultrastructural localization of gamma glutamyl transpeptidase in rat kidney and jejunum. FEBS Lett 1979, 107, 436−440.
- Pompella A, Paolicchi A, Dominici S, Comporti M, Tongiani R: Selective colocalisation of lipid peroxydation and protein thiol loss in chemically induced hepatic preneoplastic lesion: The role of gamma glutamyltranspeptidase activity. Histochem Cell Biol 1996, 106, 275–282.
- Paolicchi A, Tongiani R, Tonarelli P, Comporti M, Pompella A: Gamma-glutamyltranspeptydase-dependent lipid peroxidation in isolated hepatocytes and HepG2 hepatoma cells. Free Radic Biol Med 1997, 22, 275–282.
- Cutrin JC, Zingaro B, Camandola S, Boveris A, Pompella A, Poli G: Contribution of g glutamyl transpeptidase to oxidative damage of ischemic rat Sidney. Kidney International 2000, 57, 526–533.
- Dominici S, Paolicchi A, Corti A, Maellaro E, Pompella A: Prooxidant reactions promoted by soluble and cellbound-glutamyltransferase activity. Methods Enzymol 2005, 401, 484–501.
- Dominici S, Paolicchi A, Lorenzini E, Maellaro E, Comporti M, Pieri L, Minotti G, Pompella A: Glutamyltransferase-dependent prooxidant reactions: a factor in multiple processes. Biofactors 2003, 17, 187–198.
- Yamamoto S, Watanabe B, Hiratake J, Tanaka R, Ohkita M, Matsumura Y: Preventive Effect of GGsTop, a Novel and Selective Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats. JPET 2011 339, 945–951.
- Cecka JM: The UNOS Renal Transplant Registry. Clin Transpl 2002, 1–20.
- Nankivell BJ, Borrows RJ, Chir B, Fung CL, O’Connell PJ, Allen RD, Chapman JR: The natural history of chronic allograft nephropathy. N Engl J Med 2003, 349, 2326–2333.