title: Plasma protein thiolation index (PTI) as a biomarker of thiol-specific oxidative stress in haemodialyzed patients.
abstract: The role of oxidative stress in patients with end stage renal disease (ESRD), which occurs at significantly higher levels than in the general population, is often underestimated in clinical practice. Emerging evidence highlights the strong correlation of oxidative stress with chronic inflammation and cardiovascular disease, which are highly prevalent in most patients on maintenance haemodialysis (HD) and are a major risk factor for mortality in this population. In this study, total plasma thiols and plasma S-thiolated proteins were measured in patients with ESRD, before and after a regular HD session, and compared to age-matched healthy subjects. We found a significant decrease in the level of total plasma thiols and, conversely, a significant increase in the level of S-thiolated proteins in these patients. In most patients, post-HD plasma level of total thiols did not differ from the one in healthy subjects, whereas plasma level of S-thiolated proteins was lower in HD patients than in age-matched healthy controls. This suggests that a single HD session restores plasma thiol redox status and re-establishes the antioxidant capacity of plasma thiols. Additionally, we determined protein thiolation index (PTI), i.e., the molar ratio between the sum of all low molecular mass thiols bound to S-thiolated plasma proteins and protein free cysteinyl residues. Patients with ESRD had a significantly higher PTI compared to age-matched healthy subjects and HD was associated with a decrease in PTI to normal, or lower than normal, levels. Although this study is limited in size, our results suggest that PTI is a useful indicator of thiol-specific oxidative stress in patients with ESRD on maintenance HD. This study also emphasizes that PTI determination is a cheap and simple tool suitable for large-scale clinical studies that could be used for routine screening of thiol-specific oxidative stress.
authors.affiliation: Department of Biosciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Colombo
authors.affiliation: Humanitas Clinical and Research Center, Nephrology Unit, Rozzano, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Reggiani
authors.affiliation: Humanitas Clinical and Research Center, Nephrology Unit, Rozzano, Milan, Italy.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Podestà
authors.affiliation: Department of Biosciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Maria Lisa
authors.initials: ML
authors.lastname: Garavaglia
authors.affiliation: Humanitas Clinical and Research Center, Clinica ortopedica e traumatologica, Rozzano, Milan, Italy.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Portinaro
authors.affiliation: Department of Biosciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Milzani
authors.affiliation: Humanitas Clinical and Research Center, Nephrology Unit, Rozzano, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Badalamenti
authors.affiliation: Department of Biosciences, Università degli Studi di Milano, Milan, Italy. Electronic address: quack@unimi.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Dalle-Donne
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D006435:Renal Dialysis; D013053:Spectrophotometry; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D013438:Sulfhydryl Compounds
keywords: Biomarker; Chronic kidney disease; End stage renal disease; Haemodialysis; Oxidative stress; Plasma thiols; Protein thiolation index; S-thiolated proteins