title: Erythrocyte glutathione transferase: a potential new biomarker in chronic kidney diseases which correlates with plasma homocysteine.
abstract: The erythrocyte glutathione S-transferase (e-GST) is a member of a superfamily of inducible enzymes involved in cell detoxification that shows an increased expression in chronic kidney disease (CKD) patients. We propose a new automated analysis procedure for e-GST activity that has been validated in 72 CKD patients and 62 maintenance hemodialysis patients (MHD). Regression analysis was carried out to assess association between e-GST activity data, main clinical variables, and plasma homocysteine (Hcy), a modified sulfur amino acid known as potential risk factor for cardiovascular disease that is increased above normal levels in more than 90% of the uremic patients. An increased e-GST activity was confirmed in MHD patients (N=62; 10.2±0.4 U/gHb) compared with healthy subjects (N=80; 5.8±0.4 U/gHb), and as an original finding, a significant increase of e-GST activity was observed in pre-dialysis CKD patients with a positive correlation with disease severity weighted according to the four stages of "Kidney Disease Outcomes Quality Initiative" classification (7.4±0.5, 8±1, 9.5±0.6, 12±1 U/gHb, respectively). No correlation was found between e-GST activity and hemoglobin, transferrin, blood iron and the markers of systemic inflammation and renal function such as alpha-1 acid glycoprotein and high-sensitive C-Reactive Protein, beta-2 microglobulin and the index of malnutrition-inflammation PINI, while a significant correlation was observed for the first time between plasma Hcy and e-GST activity (r2=0.64, P<0.0001) in MHD patients. Hcy, however, was not identified as an inhibitor of e-GST enzyme. The results in this study suggest the potential for automated e-GST analysis as a valuable tool to further explore phase II-related uremic toxicity in CKD and MHD patients.
authors: Department of Laboratory Medicine, University of Rome Tor Vergata, Rome, Italy.
authors: Mariarita
authors: M
authors: Dessì
authors: Annalisa
authors: A
authors: Noce
authors: Kutayba F
authors: KF
authors: Dawood
authors: Francesco
authors: F
authors: Galli
authors: Massimo
authors: M
authors: Taccone-Gallucci
authors: Raffaele
authors: R
authors: Fabrini
authors: Alessio
authors: A
authors: Bocedi
authors: Renato
authors: R
authors: Massoud
authors: Giorgio
authors: G
authors: Fucci
authors: Anna
authors: A
authors: Pastore
authors: Simone
authors: S
authors: Manca di Villahermosa
authors: Viviana
authors: V
authors: Zingaretti
authors: Giorgio
authors: G
authors: Federici
authors: Giorgio
authors: G
authors: Ricci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005982:Glutathione Transferase / Q000097:blood* / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000175:diagnosis; D007674:Kidney Diseases / Q000097:blood* / Q000175:diagnosis*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D005982:Glutathione Transferase