Sonja Suvakov1,2, Djurdja Jerotic1, Tatjana Damjanovic3, Natasa Milic2,4, Tatjana Pekmezovic5, Tatjana Djukic1, Zorana Jelic-Ivanovic6, Ana Savic Radojevic1, Marija Pljesa-Ercegovac1, Marija Matic1, Lana McClements7,8, Nada Dimkovic4, Vesna D Garovic2, Robert C Albright2, Tatjana Simic9,10. 1. Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA. 3. Clinical Department for Renal Diseases, Zvezdara University Medical Center, Belgrade, Serbia. 4. Institute of Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 5. Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 6. Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. 7. School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia. 8. Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom. 9. Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, tatjana.simic@med.bg.ac.rs. 10. Serbian Academy of Sciences and Arts, Belgrade, Serbia, tatjana.simic@med.bg.ac.rs.
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.
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 ESRDpatient 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 ESRDpatients. This biomarker signature could enable better monitoring of patients and stratification into appropriate treatment groups.
Authors: Petar Djuric; Sonja Suvakov; Tatjana Simic; Dragana Markovic; Djurdja Jerotic; Aleksandar Jankovic; Ana Bulatovic; Jelena Tosic Dragovic; Tatjana Damjanovic; Jelena Marinkovic; Radomir Naumovic; Nada Dimkovic Journal: Toxins (Basel) Date: 2020-05-27 Impact factor: 4.546
Authors: Djurdja Jerotic; Marija Matic; Sonja Suvakov; Katarina Vucicevic; Tatjana Damjanovic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Vesna Coric; Aleksandra Stefanovic; Jasmina Ivanisevic; Zorana Jelic-Ivanovic; Lana McClements; Nada Dimkovic; Tatjana Simic Journal: Toxins (Basel) Date: 2019-07-23 Impact factor: 4.546
Authors: Djurdja Jerotic; Sonja Suvakov; Marija Matic; Abdelrahim Alqudah; David J Grieve; Marija Pljesa-Ercegovac; Ana Savic-Radojevic; Tatjana Damjanovic; Nada Dimkovic; Lana McClements; Tatjana Simic Journal: Oxid Med Cell Longev Date: 2021-01-25 Impact factor: 6.543