8-hydroxy-2--deoxyguanosine and Renal-Insufficiency--Chronic

Kidney-related pathologies have increasing prevalence rates, produce a considerable financial burden, and are characterized by elevated levels of oxidative stress (OS).. This review examines relationships between chronic kidney disease (CKD) and markers of OS and antioxidant status (AS).. A systematic review of MEDLINE-indexed clinical trials, randomized controlled trials and comparative studies that examined OS and AS was performed.. Several markers emerged as well-suited indicators of OS and AS in CKD: malondialdehyde, F2-isoprostanes, lipid hydroperoxides, asymmetric dimethylarginine, 8-oxo-7,8-dihydro-2'-deoxyguanosine, protein carbonyls, advanced oxidation protein products and glutathione-related activity.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Advanced Oxidation Protein Products; Arginine; Biomarkers; Clinical Trials as Topic; Deoxyguanosine; F2-Isoprostanes; Glutathione; Humans; Kidney; Lipid Peroxidation; Lipid Peroxides; Malondialdehyde; Oxidative Stress; Protein Carbonylation; Renal Insufficiency, Chronic

Cilnidipine, an L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles. However, the precise mechanism of the renoprotective effect of cilnidipine remains unknown. Because cilnidipine exerted significantly higher antioxidant activity than amlodipine in cultured human mesangial cells, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing oxidative stress. A total of 35 hypertensive patients receiving a renin-angiotensin system inhibitor were randomly assigned to a cilnidipine (n=18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n=17; 5 mg per day amlodipine titrated to 10 mg per day) group; the target blood pressure (BP) was set at 130/85 mmHg. After 6 months of treatment, systolic and diastolic BPs were significantly reduced in both of the groups, without any significant difference between the groups. The urinary albumin, 8-hydroxy-2'-deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (P<0.05) compared with those in the amlodipine group. The reductions in urinary albumin, 8-OHdG and L-FABP were not correlated with the change in systolic BP. In conclusion, cilnidipine, but not amlodipine, ameliorated urinary albumin excretion and decreased urinary 8-OHdG and L-FABP in the hypertensive patients. Cilnidipine probably exerts a greater renoprotective effect through its antioxidative properties.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Albuminuria; Amlodipine; Antihypertensive Agents; Antioxidants; Blood Pressure; Calcium Channel Blockers; Deoxyguanosine; Dihydropyridines; Fatty Acid-Binding Proteins; Female; Heart Rate; Humans; Hypertension; Incidence; Male; Middle Aged; Oxidative Stress; Prospective Studies; Renal Insufficiency, Chronic

Dyslipidemia is a common complication of chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality of CKD patients.. The aim of the present study was to determine whether fluvastatin, which is mostly characterized by its pleiotropic anti-oxidant effects, has renoprotective effects in dyslipidemic patients with CKD.. In 43 dyslipidemic patients with CKD taking fluvastatin 10 mg/day, 20 mg/day or 30 mg/day, renal functions as well as lipid profiles were assessed.. After 3 months of treatment with fluvastatin, LDL-cholesterol level significantly decreased. Serum creatinine level, estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), urinary liver-type fatty acid binding protein (L-FABP) level and urinary 8-hydroxydeoxyguanosine (8-OHdG) level did not change in overall patients. However, in patients with microalbuminuria (baseline UAE ≥ 30 mg/g·creatinine; n = 23), the UAE significantly decreased [2.43 ± 0.67 to 1.98 ± 0.80 log(mg/g·creatinine), p = 0.01]. In patients with high L-FABP group (baseline L-FABP ≥ 11 µg/g·creatinine; n = 18), the urinary L-FABP level was significantly decreased (1.52 ± 0.45 to 1.26 ± 0.43 µg/g·creatinine, p < 0.01). In the limited 23 patients with microalbuminuria, the L-FABP level was significantly decreased [1.20 ± 0.62 to 1.03 ± 0.49 log(µg/g·creatinine), p = 0.042], although the LDL-cholesterol level (139 ± 28 to 129 ± 23 mg/dL, p = 0.08) only showed a tendency to decrease. The 8-OHdG level also was significantly decreased (13.6 ± 9.6 to 9.8 ± 3.8 ng/g·creatinine, p = 0.043). In the overall patients, changes in the values for UAE and urinary L-FABP were not correlated with the changes in LDL-levels.. Fluvastatin reduces both UAE and the urinary L-FABP level, and thus, has renoprotective effects, independent of its lipid lowering effects in dyslipidemic patients with CKD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Albuminuria; Cholesterol, LDL; Creatinine; Deoxyguanosine; Dyslipidemias; Fatty Acid-Binding Proteins; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Renal Insufficiency, Chronic; Treatment Outcome

Oxidative stress is associated with the development and progression of chronic kidney disease (CKD) in humans. The aim of this study was to evaluate the concentrations of oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), in the plasma and urine of cats with different stages of CKD.. Plasma and urine samples were collected from cats with CKD that were referred to the Veterinary Medical Center of the University of Tokyo between April 2019 and October 2022. Plasma and urine samples were collected from healthy cats (n = 6 at most), cats with stage 2 CKD (n = 8) and stage 3-4 CKD (n = 12), and cats with idiopathic cystitis (disease control, n = 5). Plasma and urine concentrations of 8-OHdG and MDA were measured using ELISA and thiobarbituric acid reactive substances assay kits, respectively.. This report shows that plasma 8-OHdG and MDA concentrations increase with the severity of feline CKD. These markers may be useful for assessing oxidative stress in cats with CKD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cat Diseases; Cats; Creatinine; Deoxyguanosine; Humans; Malondialdehyde; Patient Acuity; Renal Insufficiency, Chronic

Air pollution, which results in the formation of polycyclic aromatic hydrocarbons (PAHs), has been identified as a cause of renal function decline and a contributor to CKD. However, the results of cross-sectional studies investigating personal, integrated biomarkers of PAHs have been mixed. Longitudinal studies may be better suited to evaluate environmental drivers of kidney decline. The purpose of this study was to examine associations of serially measured urinary PAH metabolites with clinical and subclinical measures of kidney function over time among children with CKD.. This study was conducted among 618 participants in the Chronic Kidney Disease in Children study, a cohort study of pediatric patients with CKD from the United States and Canada, between 2005 and 2015. In serially collected urine samples over time, nine PAH metabolites were measured. Clinical outcomes measured annually included eGFR, proteinuria, and BP. Subclinical biomarkers of tubular injury (kidney injury molecule-1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) and oxidant stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and F. Children were followed over an average (SD) of 3.0 (1.6) years and 2469 study visits (mean±SD, 4.0±1.6). Hydroxynaphthalene (NAP) or hydroxyphenanthrene (PHEN) metabolites were detected in >99% of samples and NAP concentrations were greater than PHEN concentrations. PHEN metabolites, driven by 3-PHEN, were associated with increased eGFR and reduced proteinuria, diastolic BP z-score, and NGAL concentrations over time. However, PAH metabolites were consistently associated with increased KIM-1 and 8-OHdG concentrations.. Among children with CKD, these findings provoke the potential explanation of reverse causation, where renal function affects measured biomarker concentrations, even in the setting of a longitudinal study. Additional work is needed to determine if elevated KIM-1 and 8-OHdG excretion reflects site-specific injury to the proximal tubule mediated by low-grade oxidant stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Child; Cohort Studies; Cross-Sectional Studies; Humans; Lipocalin-2; Longitudinal Studies; Oxidants; Polycyclic Aromatic Hydrocarbons; Proteinuria; Renal Insufficiency, Chronic; United States

Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early stages of CKD. Thus, traditional and non-traditional or uremic-related factors represent a link between CKD and cardiovascular risk. Among non-conventional risk factors, particular focus has been placed on anaemia, mineral and bone disorders, inflammation, malnutrition and oxidative stress and, in this regard, connections have been reported between oxidative stress and cardiovascular disease in dialysis patients.. We evaluated the oxidation process in different molecular lines (proteins, lipids and genetic material) in 155 non-dialysis patients at different stages of CKD and 45 healthy controls. To assess oxidative stress status, we analyzed oxidized glutathione (GSSG), reduced glutathione (GSH) and the oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators, including malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG).. An active grade of oxidative stress was found from the early stages of CKD onwards, which affected all of the molecular lines studied. We observed a heightened oxidative state (indicated by a higher level of oxidized molecules together with decreased levels of antioxidant molecules) as kidney function declined. Furthermore, oxidative stress-related alterations were significantly greater in CKD patients than in the control group.. CKD patients exhibit significantly higher oxidative stress than healthy individuals, and these alterations intensify as eGFR declines, showing significant differences between CKD stages. Thus, future research is warranted to provide clearer results in this area.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Chronic Disease; Humans; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Renal Insufficiency, Chronic

Activation of the renin angiotensin system and renal oxidative stress (OS) are critical contributors in the progression of chronic kidney disease(CKD). Recent studies have confirmed that the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas(ACE2/Ang(1-7)/Mas) axis, the important components of renin angiotensin system, protected kidneys against damage by antagonizing angiotensin II and attenuating OS in rats with several nephropathy models, but its effect needs to be further evaluated in clinic. In this study, we aimed to detected serum ACE2/Ang (1-7)/Mas axis, OS conditions and described its clinical associations in patients with CKD at different stages.A total of 48 patients with CKD and 6 healthy controls (CT) were enrolled, and serum angiotensin converting enzyme (ACE), ACE2, Ang (1-7), 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined by ELISA. Serum extracellular glutathione peroxidase(eGSH-Px) activity and renal functions were determined by the biochemical method.Serum ACE and ACE2 levels in CKD stages 3 to 5 and serum Ang(1-7) levels in CKD stages 4 to 5 without Ang II receptor blockers treatment significantly increased compared to those in the CT group. However, ACE2 was decreased and Ang(1-7) level increased in early CKD stage with Ang II receptor blockers treatment. Higher serum 8-OHdG levels and lower eGSH-Px activity were noted in CKD stages 4 to 5. Serum 8-OHdG level was correlated with serum ACE2, Ang(1-7) expression. Estimated glomerular filtration rate (eGFR) was correlated with serum ACE, ACE2, Ang(1-7), 8-OHdG, Hcy levels and serum eGSH-Px activity. Multiple-regression analysis eGFR was predicted by ACE, Hcy, eGSH-Px, and also can be predicted by ACE2, Ang(1-7), Hcy in CT subgroup.The ACE2/Ang(1-7)/Mas axis is associated with OS, and both them were associated with eGFR in the progression of CKD. Activation of ACE2/Ang(1-7)/Mas axis may have renoprotective effect and can be a potential therapeutic target in patients with early CKD stages.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Angiotensin I; Angiotensin II; Case-Control Studies; Female; Humans; Male; Middle Aged; Oxidative Stress; Peptide Fragments; Peptidyl-Dipeptidase A; Pilot Projects; Renal Insufficiency, Chronic; Renin-Angiotensin System

Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD.. Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) and white (58.3%), and participants had a median age of 11.0 years (interquartile range 7.6 to 14.6) at the baseline visit. In urine samples collected serially over an average of 3.0 years (standard deviation [SD] 1.6), concentrations of BPA, phthalic acid (PA), and phthalate metabolites were measured as well as biomarkers of tubular injury (kidney injury molecule-1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) and oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and F2-isoprostane). Clinical renal function measures included estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure. Linear mixed models were fit to estimate the associations between urinary concentrations of 6 chemical exposure measures (i.e., BPA, PA, and 4 phthalate metabolite groups) and clinical renal outcomes and urinary concentrations of KIM-1, NGAL, 8-OHdG, and F2-isoprostane controlling for sex, age, race/ethnicity, glomerular status, birth weight, premature birth, angiotensin-converting enzyme inhibitor use, angiotensin receptor blocker use, BMI z-score for age and sex, and urinary creatinine. Urinary concentrations of BPA, PA, and phthalate metabolites were positively associated with urinary KIM-1, NGAL, 8-OHdG, and F2-isoprostane levels over time. For example, a 1-SD increase in ∑di-n-octyl phthalate metabolites was associated with increases in NGAL (β = 0.13 [95% CI: 0.05, 0.21], p = 0.001), KIM-1 (β = 0.30 [95% CI: 0.21, 0.40], p < 0.001), 8-OHdG (β = 0.10 [95% CI: 0.06, 0.13], p < 0.001), and F2-isoprostane (β = 0.13 [95% CI: 0.01, 0.25], p = 0.04) over time. BPA and phthalate metabolites were not associated with eGFR, proteinuria, or blood pressure, but PA was associated with lower eGFR over time. For a 1-SD increase in ln-transformed PA, there was an average decrease in eGFR of 0.38 ml/min/1.73 m2 (95% CI: -0.75, -0.01; p = 0.04). Limitations of this study included utilization of spot urine samples for exposure assessment of non-persistent compounds and lack of specific information on potential sources of exposure.. Although BPA and phthalate metabolites were not associated with clinical renal endpoints such as eGFR or proteinuria, there was a consistent pattern of increased tubular injury and oxidative stress over time, which have been shown to affect renal function in the long term. This raises concerns about the potential for clinically significant changes in renal function in relation to exposure to common environmental toxicants at current levels.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Benzhydryl Compounds; Biomarkers; Canada; Child; Cohort Studies; Creatinine; F2-Isoprostanes; Female; Glomerular Filtration Rate; Hepatitis A Virus Cellular Receptor 1; Humans; Kidney; Kidney Function Tests; Lipocalin-2; Longitudinal Studies; Male; Oxidative Stress; Phenols; Phthalic Acids; Renal Insufficiency, Chronic; United States

Oxidative stress and low-grade systemic inflammation are common interrelated sequelae of chronic kidney disease (CKD) that associate with mortality. We investigated the association of serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, with mortality in CKD individuals and analyzed whether inflammation modifies the association.. In 376 individuals with a wide range of estimated glomerular filtration rate (eGFR); >60 ml/min (n = 53), 15-60 ml/min (n = 60) and <15 ml/min (n = 263), cut-off values of serum 8-OHdG, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF) as predictors of mortality were determined by ROC curves. We analyzed associations of 8-OHdG with inflammation markers and the overlapping effect of hsCRP, IL-6 and TNF on the association between 8-OHdG and all-cause mortality by multivariate generalized linear models.. In separate individual exposure analyses, higher 8-OHdG, hsCRP, and IL-6 (but not TNF) were each independently associated with increased risk of death in multivariate models adjusted for age, sex, diabetes mellitus, cardiovascular disease, protein-energy wasting, cohort calendar year, blood sample storage time and eGFR. For 8-OHdG, the multivariate relative risk ratio, RR. Serum 8-OHdG, a biomarker of oxidative DNA damage, is associated with increased all-cause mortality risk in individuals with a wide range of eGFR and this association is independent of inflammation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; C-Reactive Protein; DNA Damage; Female; Glomerular Filtration Rate; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Oxidative Stress; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylation; Age Factors; Aging; Albuminuria; Animals; Cell Cycle Proteins; Cellular Senescence; Deoxyguanosine; Forkhead Box Protein O3; Forkhead Transcription Factors; Gene Knockdown Techniques; Genotype; Glomerulonephritis; Mice; Oxidative Stress; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phenotype; Podocytes; Renal Insufficiency, Chronic; RNA Interference; RNA, Small Interfering; Signal Transduction; Sirtuin 1; Transcription Factor RelA

Chronic kidney disease (CKD) is associated with an inflammation-mediated process, and the vitamin D (3) catabolizing enzyme, CYP24, is frequently overexpressed in CKD, where it may play a crucial role in kidney disease.. Herein, in this study, we investigated CYP24, reactive oxygen species (ROS), and inflammatory responses in an indoxyl sulfate (IS)-induced CKD model to elucidate the role of CYP24 in CKD.. Our results showed that IS upregulates proinflammatory cytokine, CYP24 and nuclear factor-κB (NF-κB) expression in human renal proximal tubule epithelial cells. In addition, IS treatment increased ROS production and simultaneously upregulated CYP24 expression and NF-κB translocation. Moreover, the IS-induced upregulation of CYP24 expression was alleviated by an inhibitor of NF-κB, as well as a siRNA specific to NF-κB p65. Furthermore, the renal cortex of DN (Dahl salt-resistant normotensive) + IS, DH (Dahl salt-sensitive hypertensive), and DH + IS rats showed increased expression of NF-κB p65, CYP24, 8-hydroxydeoxyguanosine (8-OHdG), a marker of ROS and macrophage infiltration compared with DN rats.. These results provide evidence that administration of IS in human renal tubular epithelial cells upregulates NF-κB, which leads to increase CYP24 expression and ROS production. They also suggest that suppressing NF-κB signalling is promising for the development into a strategy for CKD treatment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cell Line, Tumor; Cytochrome P450 Family 24; Cytokines; Deoxyguanosine; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hypertension; Indican; Inflammation Mediators; Kidney; Oxidative Stress; Rats, Inbred Dahl; Reactive Oxygen Species; Renal Insufficiency, Chronic; RNA Interference; Transcription Factor RelA; Transfection; Up-Regulation

Chronic kidney disease (CKD) is frequently associated with uremic encephalopathy and cognitive impairment. Recent studies have demonstrated that cerebral oxidative stress contributes to cognitive dysfunction. Although oxidative stress has been reported to increase in the uremic rat brain, the relationship between increased oxidative stress and cognitive impairment in uremia is unclear. In the present study, the effects of tempol (TMP), an antioxidant drug, were investigated in uremic mice.. CKD was induced in male C57BL/6 mice (n = 8) by left nephrectomy and 2/3 electrocoagulation of the right renal cortex. Working memory performance was tested by the radial arm water maze test. We have prepared two protocols ('time course study' and 'treatment study'). First, we examined the working memory test and histological examination of mouse brains after 4 and 8 weeks. Next, we investigated the effect of TMP (3 mM) against uremia-induced neurodegeneration and oxidative stress in the mouse brain.. Eight weeks after CKD induction, vehicle-treated mice made significantly more errors than sham-operated control mice, while TMP improved working memory performance in CKD mice. CKD was associated with accumulation of 8-hydroxy-2'-deoxyguanosine in the hippocampal neuronal cells, but not in TMP-treated CKD mice. Increased numbers of pyknotic neuronal cells were observed in the hippocampus of CKD mice at 8 weeks, but pyknotic neuronal cell numbers were decreased under the influence of TMP in uremic mice.. The present study provided evidence that uremia is associated with spatial working memory dysfunction in mice and that treatment with TMP protects against cerebral oxidative stress and improves cognitive dysfunction in uremic mice, suggesting their potential usefulness for the treatment of cognitive dysfunction in uremia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Cognition Disorders; Cyclic N-Oxides; Deoxyguanosine; Drug Evaluation, Preclinical; Hippocampus; Male; Maze Learning; Memory Disorders; Memory, Short-Term; Mice, Inbred C57BL; Neuroprotective Agents; Oxidative Stress; Renal Insufficiency, Chronic; Spatial Memory; Spin Labels; Uremia

Patients with chronic kidney disease (CKD) have signs of genomic instability and, as a consequence, extensive genetic damage, possibly due to accumulation of uraemic toxins, oxidative stress mediators and other endogenous substances with genotoxic properties. We explored factors associated with the presence and background levels of genetic damage in CKD. A cross-sectional study was performed in 91 CKD patients including pre-dialysis (CKD patients; n = 23) and patients undergoing peritoneal dialysis (PD; n = 33) or haemodialysis (HD; n = 35) and with 61 healthy subjects, divided into two subgroups with the older group being in the age range of the patients, serving as controls. Alkaline comet assay and cytokinesis-block micronucleus assay in peripheral blood lymphocytes were used to determine DNA and chromosome damage, respectively, present in CKD. Markers of oxidative stress [malondialdehyde (MDA), advanced glycation end products (AGEs), thiols, advanced oxidation protein products and 8-hydroxy-2'-deoxyguanosine] and markers of inflammation (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were also measured. Micronucleus (MN) frequency was significantly higher (P < 0.05) in the CKD group (46±4‰) when compared with the older control (oC) group (27.7±14). A significant increase in MN frequency (P < 0.05) was also seen in PD patients (41.9±14‰) versus the oC group. There was no statistically significant difference for the HD group (29.7±15.6‰; P = NS) versus the oC group. Comet assay data showed a significant increase (P < 0.001) of tail DNA intensity in cells of patients with CKD (15.6±7%) with respect to the total control (TC) group (11±1%). PD patients (14.8±7%) also have a significant increase (P < 0.001) versus the TC group. Again, there was no statistically significant difference for the HD group (12.5±3%) compared with the TC group. Patients with MN values in the upper quartile had increased cholesterol, triglycerides, AGEs and MDA levels and lower albumin levels. Multiple logistic regression analysis showed that male gender, diabetes and treatment modality were independently associated with higher levels of DNA damage. Our results suggest that oxidative stress, diabetes, gender and dialysis modality in CKD patients increased DNA and chromosome damage. To confirm these data, prospective clinical trials need to be performed.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; C-Reactive Protein; Chromosomal Instability; Comet Assay; Cross-Sectional Studies; Deoxyguanosine; DNA Damage; Female; Glycation End Products, Advanced; Humans; Inflammation; Interleukin-6; Logistic Models; Lymphocytes; Male; Malondialdehyde; Micronucleus Tests; Middle Aged; Oxidative Stress; Peritoneal Dialysis; Renal Dialysis; Renal Insufficiency, Chronic; Serum Albumin; Triglycerides; Tumor Necrosis Factor-alpha

Increased vascular calcification and oxidative stress are considered as extra renal risk factors at the pathogenesis cardiovascular events in chronic kidney disease (CKD). We investigated matrix Gla protein (MGP) (T-138C, Glu60X, Thr83Ala) and Klotho (Cys370Ser) gene polymorphisms, serum MGP levels, and oxidative stress status of 84 CKD patients and 37 healthy controls. The MGP gene Glu60X and Thr83Ala polymorphisms were significantly associated with CKD. The correlation between T-138C genotype of MGP gene, Cys370Ser genotype of Klotho gene, and CKD was not significant (p > 0.05). At the haplotype analysis, the combination of the X allele of Glu60X and the Thr allele of Thr83Ala showed a significantly increased risk of CKD (p < 0.05). X allele, Thr allele, and C allele of T-138C were associated with diabetes mellitus and CKD phenotypes occurring concurrently (p < 0.01). Serum zinc levels were significantly low in end-stage renal disease (ESRD) patients (p = 0.0001). The total comet score frequency of ESRD patients was higher than that of control group (p < 0.05). The urinary 8-hydroxy-2'-deoxyguanosine levels were significantly high in CKD patients (p < 0.05). According to this study, analyzing the distribution of MGP gene and oxidative stress status would be very informative in order to detect their role at CKD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Calcium-Binding Proteins; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Deoxyguanosine; Extracellular Matrix Proteins; Female; Genotype; Glucuronidase; Humans; Kidney Failure, Chronic; Klotho Proteins; Male; Matrix Gla Protein; Middle Aged; Oxidative Stress; Polymerase Chain Reaction; Polymorphism, Genetic; Prognosis; Reference Values; Renal Dialysis; Renal Insufficiency, Chronic; Severity of Illness Index; Statistics, Nonparametric; Young Adult