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 language | English (US) |
|---|---|
| Journal | American Journal of Nephrology |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- Endothelial dysfunction
- Gene polymorphism
- Haemodialysis
- Oxidative stress
- Survival analysis
ASJC Scopus subject areas
- Nephrology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival
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
PY - 2019/1/1
Y1 - 2019/1/1
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
UR - http://www.scopus.com/inward/record.url?scp=85068526930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068526930&partnerID=8YFLogxK
U2 - 10.1159/000501300
DO - 10.1159/000501300
M3 - Article
JO - American Journal of Nephrology
JF - American Journal of Nephrology
SN - 0250-8095
ER -