Serum Glutaredoxin Activity as a Marker of Oxidative Stress in Chronic Kidney Disease: A Pilot Study

Abstract

Background: Inflammation and oxidative stress play important roles in the pathogenesis and progression of chronic kidney disease (CKD) and in its complications, in particular cardiovascular disease, a major cause of death among patients undergoing dialysis treatment. We recently described that Glutaredoxin1 (Grx), an intracellular antioxidant, catalyzes oxidoreductase reactions also extracellularly, and that serum Grx levels correlate to disease severity in type 2 diabetes. Aim: In the current study we assess Grx as a potential clinical marker of oxidative stress in CKD. Methods: We examined Grx activity in 25 patients with different stages of chronic kidney failure, 19 control subjects, and 36 patients at initiation of dialysis and after 2 years of dialysis. Results: We found that Grx activity was significantly higher in CKD patients compared to control subjects, indicating an oxidized extracellular environment in CKD. Grx levels correlated to interleukin-6 and pentosidine, but not to age or GFR. In dialysis patients with Grx sampling before dialysis start and after 2 years of dialysis, Grx levels increased more in hemodialysis (HD) patients than in peritoneal dialysis patients, indicating an increased oxidative stress imbalance in HD patients. Patients who experienced a stroke or myocardial infarction at any time had a significantly higher increase in Grx during the 2 years of dialysis, compared to patients without stroke or myocardial infarction, indicating a possible association between high Grx levels and a cardiovascular event. Conclusion: Our pilot study indicates that Grx may be a useful marker for assessing the degree of oxidative stress in CKD, however this needs further investigation in a larger prospective patient cohort.

Processed Meat Protein Promoted Inflammation and Hepatic Lipogenesis by Upregulating Nrf2/Keap1 Signaling Pathway in Glrx-Deficient Mice

“…Glrx is a primary redox enzyme and a multieffect cytokine that takes part in cellular growth, apoptosis, cytoskeletal regulation, angiogenesis, inflammation, and protection of cells against oxidative stress. , Quantitative proteome and metabolome analyses revealed that Grx1 knockdown decreased the cellular level of GSH but increased ROS production, resulting in activation of p53 and associated signaling pathways . Grx is considered as a potential biomarker and key factor in the pathogenesis of chronic kidney disease and diabetes. , In physiology, Grx1 regulates nuclear factor-E2-related factor 2/Kelch-like ECH-associated protein1 (Nrf2/Keap1), nuclear factor κB (NF-kB), interleukin 1 beta (IL-1β) glutathionylation, and sirtuin 1 activity. − The deficiency of Glrx1 in mice would promote the development of obesity, hyperlipidemia, and NAFLD under a high-fat diet mode . However, the effect of Glrx1 in NAFLD induced by oxidative stress as a result of processed meat proteins remains largely elusive.…”

“…26 Grx is considered as a potential biomarker and key factor in the pathogenesis of chronic kidney disease and diabetes. 27,28 In physiology, Grx1 regulates nuclear factor-E2-related factor 2/Kelch-like ECHassociated protein1 (Nrf2/Keap1), nuclear factor κB (NF-kB), interleukin 1 beta (IL-1β) glutathionylation, and sirtuin 1 activity. 29−32 The deficiency of Glrx1 in mice would promote the development of obesity, hyperlipidemia, and NAFLD under a high-fat diet mode.…”

Evaluation of Glutaredoxin 1 as a Novel Marker of Renal Damage after Ischemia‐Reperfusion Injury in Mice

“…In a previous work, we detected increased levels of Grx1 in the urine of mice 24h after renal IRI 1. Recently, Grx1 was shown to be elevated in the serum of patients with chronic kidney disease 2. To determine the usefulness of Grx1 as a possible biomarker of ischemic renal damage we evaluated serum, urinary, as well as intra‐renal levels of Grx1 in a mouse model of renal IRI.…”