minimal role of HH as causal factor of, or simple asso- ciation with, vascular injury in CKD. Other aspects of the defective homeostasis of blood thiols in CKD include a disturbance of redox pairs, such as GSH/GSSG and cysteine/cystine, in plasma and blood cells [2,10,11] that is suggested to mirror the occurrence of oxidative stress in these patients [5]. Protein thiols are also modified [1,12,13] and a defective antioxidant function of albumin, the main protein thiol of human plasma reacting with physiological peroxides [14] and several elecrophiles [15], has been described in CKD [16] together with decoration by carbonyls and glyca- tion epitopes [17,18]. Moreover, some of us also demonstrated the redox unbalance of uremic red blood cells (RBC) GSH/GSSH is decreased in both extracorporeal [19] and peritoneal dial- ysis (PD) [10] patients suffering of severe anemia and in PD this biochemical trait was associated with a defective redox of pyridine nucleotide pairs, namely NADH/NAD  and NADPH/NADP  [19]. This impaired GSH redox in the uremic RBC is now confirmed by other and more Blood thiol status and erythrocyte glutathione-S-transferase in chronic kidney disease patients on treatment with frequent (daily) hemodialysis F. Galli 1 * , M. Piroddi 1 , D. Bartolini 1 , S. Ciffolilli 1 , E. Buoncristiani 2 , G. Ricci 3 & U. Buoncristiani 1 * ^ 1 Department of Internal Medicine, Laboratory of Clinical Biochemistry and Nutrition, University of Perugia, Perugia, Italy, 2 Nephrology Unit, “Branca” Hospital, Gubbio, Italy, and 3 Department of Chemical Sciences and Technologies, University of Rome “Tor Vergata”, Italy Abstract Background. Chronic kidney disease (CKD) is a condition of impaired homeostasis of blood thiols characterized by a severe hyperho- mocysteinemia (HH) and abnormal expression of the red blood cell glutathione (GSH)-consuming enzyme GSH S-transferase (eGST) (Galli et al., Clin Chem 1999). The correlation between plasma Hcy and eGST recently identified by our group (Dessì et al., Amino Acids 2012) suggests a role of this detoxifying enzyme in the impaired thiol status of CKD treated with hemodialysis therapy (HD). This retrospective study is aimed at investigating whether frequent HD can alleviate these biochemical symptoms of CKD. Methods. Labora- tory data of a population of 98 HD patients investigated for plasma Hcy and blood thiol status between 1999 and 2004 were examined. A frequent HD method carried out with a 2-h daily schedule (daily HD) (DHD) was compared with standard 4-h  3/week protocol of HD (SHD) in either cross-sectional ( n  70 SHD vs. n  28 DHD) and prospective A-B design ( n  18 SHD patients shifted to DHD). Results. The results demonstrate that DHD produces a better correction than SHD of the uremic retention solute Hcy as well as of Cys and Cys-Gly measured in plasma. Such a correction effect of DHD on HH correlates with that on the detoxification enzyme eGST and on pGSH. Conclusions. These findings point to a role of frequent dialysis in the depuration of uremic retention solutes that may interfere with thiol metabolism and redox in HD patients. These solutes may include substrates of eGST that await further investigation for molecular identification and better removal by more efficient dialysis therapies. Keywords: daily hemodialysis, blood thiols, homocysteine, glutathione, glutathione S-transferase, uremic toxins Introduction An impaired homeostasis of blood thiols has been repeat- edly described in chronic kidney disease (CKD) reaching highest level of expression in end-stage patients on hemo- dialysis (HD) therapy [1–4]. Underlying events of this defect may include a defective thiol metabolism of kidney and then of other tissues exposed to uremic toxins, as well as metabolic consequences of uremic comorbidity that includes chronic inflammation, malnutrition, anemia and oxidative stress (reviewed in [5]). Hyperhomocysteinemia (HH) is a highly prevalent bio- chemical defect of CKD. As an independent risk factor for atherothrombotic pathologies that are leading cause of morbidity and mortality in these patients (i.e. myocardial infarction and stroke), HH is the most investigated disor- der of blood thiols in these patients (recently reviewed in [6]) with possible detrimental effects on the homeostasis of proteins and nucleic acids [7,8]. Notwithstanding, Hcy- lowering therapy does not seem to affect the unfavorable cardiovascular prognosis of CKD [9], thus suggesting * These authors provided the same contribution to the coordination and execution of this research. ^As past director of the Nephrology and Dialysis Unit, “R. Silvestrini” Regional Hospital, Perugia Italy, BU was clinical supervisor of the studies that originated the laboratory database used in this study. He is Emeritus of Nephrology at the University of Perugia. Correspondence: Francesco Galli, PhD, Department of Internal Medicine , Laboratory of Clinical Biochemistry and Nutrition, University of Perugia, Via del Giochetto, 06126 Perugia, Italy. Tel/Fax:  39 075 585 7445. E-mail: f.galli@unipg.it (Received date: 30 September 2013; Accepted date: 30 October 2013; Published online: 14 January 2014) Free Radical Research, 2014; Early Online: 1–9 © 2014 Informa UK, Ltd. ISSN 1071-5762 print/ISSN 1029-2470 online DOI: 10.3109/10715762.2013.861901 ORIGINAL ARTICLE Free Radic Res Downloaded from informahealthcare.com by Rachel Andrews on 01/20/14 For personal use only.