Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival.

Abstract

INTRODUCTION:

Overall survival of patients with end-stage renal disease (ESRD) remains poor. Oxidative stress is one of the major risk factors associated with mortality in this patient group. As glutathione S-transferases (GST) are well-established antioxidants, we hypothesized that a model including GST gene polymorphisms, oxidative damage byproducts and cell adhesion markers has a prognostic role in ESRD patient survival.

METHODS:

A prospective study of 199 patients with ESRD on haemodialysis was conducted. GST genotype, oxidative stress byproducts and cell adhesion molecules were measured in plasma. Multivariate Cox regression and Kaplan-Meier survival analyses were performed to test the predictive ability of these parameters in the 8-year follow-up period.

RESULTS:

GSTM1-null genotype was associated with significantly shorter overall (HR 1.6, p = 0.018) and cardiovascular-specific (HR 2.1, p = 0.010) survival. Oxidative stress byproducts (advanced oxidation protein products [AOPP], prooxidant-antioxidant balance [PAB], malondialdehyde [MDA]) and cell adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1] and soluble intercellular adhesion molecule-1 [sICAM-1]) demonstrated a significant predictive role in terms of overall and cardiovascular survival. When 6 biomarkers (GSTM1 genotype, high AOPP/PAB/MDA/-sVCAM-1/sICAM-1) were combined into a scoring model, a significantly shorter overall and cardiovascular survival was observed for patients with the highest score (p < 0.001).

CONCLUSION:

We identified a novel panel of biomarkers that can be utilized in predicting survival in ESRD patients. This biomarker signature could enable better monitoring of patients and stratification into appropriate treatment groups.

• Authors: Sonja Suvakov, Djurdja Jerotic, Tatjana Damjanovic, Natasa Milic, Tatjana Pekmezovic, Tatjana Djukic, Zorana Jelic-Ivanovic, Ana Savic Radojevic, Marija Pljesa-Ercegovac, Marija Matic, Lana McClements, Nada Dimkovic, Vesna D Garovic, Robert C Albright, Tatjana Simic
• Journal: American journal of nephrology (Am J Nephrol) Vol. 50 Issue 2 Pg. 115-125 ( 2019) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 31238306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 S. Karger AG, Basel.

Chemical References

• Biomarkers
• ICAM1 protein, human
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Malondialdehyde
• Glutathione Transferase

Topics

• Aged
• Biomarkers (analysis)
• Cardiovascular Diseases (blood, etiology, mortality)
• Clinical Decision-Making
• Endothelium, Vascular (metabolism, physiopathology)
• Female
• Follow-Up Studies
• Glutathione Transferase (genetics)
• Humans
• Intercellular Adhesion Molecule-1 (blood, metabolism)
• Kaplan-Meier Estimate
• Kidney Failure, Chronic (complications, genetics, mortality, therapy)
• Male
• Malondialdehyde (blood, metabolism)
• Middle Aged
• Oxidative Stress
• Patient Selection
• Polymorphism, Single Nucleotide
• Predictive Value of Tests
• Prospective Studies
• Renal Dialysis
• Risk Assessment (methods)
• Vascular Cell Adhesion Molecule-1 (blood, metabolism)