Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalAmerican Journal of Nephrology
DOIs
StatePublished - Jan 1 2019

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Renal Dialysis
Oxidative Stress
Chronic Kidney Failure
Survival
Advanced Oxidation Protein Products
Glutathione Transferase
Vascular Cell Adhesion Molecule-1
Antioxidants
Biomarkers
Genotype
Cell Adhesion Molecules
Intercellular Adhesion Molecule-1
Malondialdehyde
Kaplan-Meier Estimate
Physiologic Monitoring
Survival Analysis
Cell Adhesion
Prospective Studies
Mortality
Genes

Keywords

  • Endothelial dysfunction
  • Gene polymorphism
  • Haemodialysis
  • Oxidative stress
  • Survival analysis

ASJC Scopus subject areas

  • Nephrology

Cite this

Suvakov, S., Jerotic, D., Damjanovic, T., Milic, N., Pekmezovic, T., Djukic, T., ... Simic, T. (2019). Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival. American Journal of Nephrology. https://doi.org/10.1159/000501300

Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival. / Suvakov, Sonja; Jerotic, Djurdja; Damjanovic, Tatjana; Milic, Natasa; Pekmezovic, Tatjana; Djukic, Tatjana; Jelic-Ivanovic, Zorana; Savic Radojevic, Ana; Pljesa-Ercegovac, Marija; Matic, Marija; McClements, Lana; Dimkovic, Nada; Garovic, Vesna D; Albright, Robert C.; Simic, Tatjana.

In: American Journal of Nephrology, 01.01.2019.

Research output: Contribution to journalArticle

Suvakov, S, Jerotic, D, Damjanovic, T, Milic, N, Pekmezovic, T, Djukic, T, Jelic-Ivanovic, Z, Savic Radojevic, A, Pljesa-Ercegovac, M, Matic, M, McClements, L, Dimkovic, N, Garovic, VD, Albright, RC & Simic, T 2019, 'Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival', American Journal of Nephrology. https://doi.org/10.1159/000501300
Suvakov, Sonja ; Jerotic, Djurdja ; Damjanovic, Tatjana ; Milic, Natasa ; Pekmezovic, Tatjana ; Djukic, Tatjana ; Jelic-Ivanovic, Zorana ; Savic Radojevic, Ana ; Pljesa-Ercegovac, Marija ; Matic, Marija ; McClements, Lana ; Dimkovic, Nada ; Garovic, Vesna D ; Albright, Robert C. ; Simic, Tatjana. / Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival. In: American Journal of Nephrology. 2019.
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AU - Suvakov, Sonja

AU - Jerotic, Djurdja

AU - Damjanovic, Tatjana

AU - Milic, Natasa

AU - Pekmezovic, Tatjana

AU - Djukic, Tatjana

AU - Jelic-Ivanovic, Zorana

AU - Savic Radojevic, Ana

AU - Pljesa-Ercegovac, Marija

AU - Matic, Marija

AU - McClements, Lana

AU - Dimkovic, Nada

AU - Garovic, Vesna D

AU - Albright, Robert C.

AU - Simic, Tatjana

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N2 - 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.

AB - 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.

KW - Endothelial dysfunction

KW - Gene polymorphism

KW - Haemodialysis

KW - Oxidative stress

KW - Survival analysis

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