Areti Makedou

Slow Intravenous Iron Administration Does Not Aggravate Oxidative Stress and Inflammatory Biomarkers during Hemodialysis: A Comparative Study between Iron Sucrose and Iron Dextran

Background/Aims: Fast intravenous (i.v.) iron administration during hemodialysis (HD) is associated with the augmentation of oxidative stress and the increase in inflammatory biomarkers, which are also induced by the hemodialysis procedure itself. The aim of this study was to investigate if slow i.v. iron administration would aggravate the status of oxidative stress and inflammatory biomarkers during a hemodialysis session. Methods: Twenty dialysis patients 30–92 years of age that were iron replete and had values for hemoglobin, transferrin saturation and serum ferritin among recommended goals were evaluated in three separate hemodialysis sessions. In the first session patients did not receive any iron treatment, whereas during the second and the third session patients received slow (60 min) i.v. infusions of 100 mg of iron sucrose and 100 mg of iron dextran, respectively. Blood samples were drawn before the hemodialysis session, 15 min after the end of iron administration and at the end of the hemodialysis session in all occasions, for the measurement of markers of oxidant stress (oxidized LDL and ischemia-modified albumin) and inflammation (high-sensitivity C-reactive protein, interleukin-6 and tumor necrosis factor-α). Results: Oxidized LDL was not significantly altered during hemodialysis and this pattern was similar between the three occasions studied. In contrast, ischemia-modified albumin was significantly increased and this effect was also not different between the net hemodialysis and the occasions of iron administration. High-sensitivity CRP, IL-6 and TNF-α were all significantly elevated during hemodialysis and again both types of iron administration did not produce significant changes in this pattern. Conclusion: We did not find an increase in the markers of oxidation/inflammation studied, after slow i.v. iron administration during hemodialysis session.

Elevated asymmetric dimethylarginine is associated with oxidant stress aggravation in patients with early stage autosomal dominant polycystic kidney disease.

Background/Aims: In experimental models of polycystic kidney disease impaired bioavailability of nitric oxide (NO) and elevated mRNA expression of oxidative stress markers at the kidney level was noted. However, clinical studies investigating the potential role of endothelial dysfunction and oxidative stress in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) are limited. We evaluated asymmetric dimethylarginine (ADMA) as marker of NO synthase inhibitor as well as 15-F2t-Isoprostane and oxidized-low density lipoprotein (oxidized-LDL) as measures of oxidative stress in patients with early stages ADPKD. Methods: We recruited 26 ADPKD patients (Group A) with modestly impaired renal function (eGFR 45-70 ml/min/1.73m2), 26 age- and sex-matched ADPKD patients (Group B) with relatively preserved renal function (eGFR)>70 ml/min/1.73m2), and 26 age- and sex-matched controls (Group C). Determination of circulating levels of ADMA, 15-F2t-Isoprostane, oxidized-LDL and routine biochemistry was performed. Results: Group A and B had significantly higher ADMA levels as compared to controls (1.68±0.7 vs 0.51±0.2 μmol/l, P<0.001 and 1.26±0.7 vs 0.51±0.2 μmol/l, P<0.001, respectively). 15-F2t-IsoP and oxidized-LDL levels were also significantly higher in Group B relative to controls (788.8±185.0 vs 383.1±86.0 pgr/ml, P<0.001 and 11.4±6.6 vs 6.4±2.6 EU/ml, P<0.05 respectively) and were further elevated in Group A. In correlation analysis, ADMA levels exhibited strong associations with levels of 15-F2t-Isoprostane (r=0.811, P<0.001) and oxidized-LDL (r=0.788, P<0.001), whereas an inverse correlation was evident between ADMA and eGFR (r=-0.460, P<0.001). Conclusion: This study shows elevation in circulating levels of ADMA along with aggravation of oxidative stress from the early stages of ADPKD.

Association between Hyperhomocysteinemia and Ultrasonographic Atherosclerotic Indices of Carotid Arteries in Chronic Hemodialysis Patients

Background: Atherosclerotic cardiovascular events are a major cause of morbidity and the main cause of mortality in hemodialysis patients. Hyperhomocysteinemia – which is a consistent finding in uremic patients – is considered an independent risk factor for cardiovascular disease (CVD). However, the relationship between plasma homocysteine (Hcy) concentrations and atherosclerotic CVD has not been extensively investigated. Patients and Methods: 37 patients undergoing chronic hemodialysis and 30 healthy individuals (control group), sex- and age-matched, were included in this study. Both healthy controls and hemodialysis patients underwent echo-Doppler carotid artery examination. The right and left carotid arteries were assessed separately. Our observation included measurements of the ultrasound images of the intimal wall thickness, the lumen diameter and the atherosclerotic plaques. We determined plasma Hcy, vitamin B12 and folic acid levels and serum cholesterol, triglycerides, HDL, ApoA-I, ApoB-100, Lp(a), CRP, albumin and creatinine levels in blood samples from both studied groups. We also determined the urea reduction ratio in the patient groups. The epidemiological as well as the biochemical data were correlated with the findings of the carotid artery examination. Results: Plasma Hcy levels were significantly increased in hemodialysis patients compared to controls (33 ± 12.3 vs. 12.27 ± 7.47 µmol/l, p < 0.001). Intimal wall thickness, lumen diameter and number of atherosclerotic plaques of both carotid arteries were significantly higher (p < 0.01 or p < 0.001) in patients compared to controls. There was a significant positive correlation between plasma Hcy levels and the number of the atherosclerotic plaques (r = 0.41, p < 0.01 in the right and r = 0.49, p < 0.001 in the left carotid artery). Lumen diameter was significantly (p < 0.01) associated with age, MAP and CRP levels. Significant correlations (p = 0.05–0.01) were also found between the number of the plaques and age as well as the duration of hemodialysis, while folic acid levels were inversely correlated with the number of the plaques. Conclusions: Both hyperhomocysteinemia and atherosclerotic indices of the carotid arteries are more prevalent in hemodialysis patients compared to healthy controls. Elevated plasma Hcy levels were associated with the carotid artery atherosclerotic indices in chronic hemodialysis patients.

Association between plasma homocysteine levels and coronary artery disease: a population-based study in northern Greece

SUMMARY Objective: Elevated plasma total homocysteine (tHcy) levels constitute a risk factor for coronary artery disease (CAD). We prospectively examined the association of fasting tHcy levels in patients in Northern Greece who had established CAD. Patients and methods: Plasma fasting tHcy levels were measured in 42 patients with angiographically documented CAD and compared to 42 age-, sex-, BMI- and smoking habit-matched control subjects. We also determined the plasma vitamin B12, folic acid and lipoprotein levels in all patients and controls. Conventional risk factors for CAD were also estimated. Results: In a univariate analysis, tHcy (jumol/l) levels were higher in patients compared to controls almost reaching statistical significance (13 (7–41) vs 11.3 (4–39); p = 0.07). Multivariate analysis of conventional risk factors showed that tHcy levels were not an independent risk factor for CAD. However, tHcy levels were significantly higher in patients with a previous history of myocardial infarction compared to patients without such a history and to controls (15 (8.8-29) vs 11.7 (7-41); p = 0.007 and 15 (8.8-29) vs 11.3 (4-39); p = 0.002, respectively). Hyperhomocysteinaemia (> 15|imol/l) was detected in 35.7% of patients and 11.9% of controls (p < 0.05). Conclusions: In Northern Greece, plasma tHcy levels may not be an independent risk factor for CAD in patients with angiographically documented CAD. However, patients with CAD have a trend towards higher tHcy levels. Additionally, plasma tHcy levels may be associated with the development of myocardial infarction.

Comparison of Glycemic Markers in Chronic Hemodialysis Using Continuous Glucose Monitoring

Background: Glycated hemoglobin A1c (HbA1c) among diabetic hemodialysis patients continues to be the standard of care, although its limitations are well recognized. This study evaluated glycated albumin (GA) and glycated serum protein (GSP) as alternatives to HbA1c in detecting glycemic control among diabetic hemodialysis patients using continuous-glucose-monitoring (CGM)-derived glucose as reference standard. Methods: A CGM system (iPRO) was applied for 7 days in 37 diabetic hemodialysis patients to determine glycemic control. The accuracy of GA and GSP versus HbA1c in detecting a 7-day average glucose ≥184 mg/dL was evaluated via receiver-operating-characteristic (ROC) analysis. Results: CGM-derived glucose exhibited strong correlation (r = 0.970, p < 0.001) and acceptable agreement with corresponding capillary glucose measurements obtained by the patients themselves in 1,169 time-points over the 7-day-long CGM. The area under ROC curve (AUC) for GA, GSP, and HbA1c to detect poor glycemic control was 0.976 (0.862–1.000), 0.682 (0.502–0.862), and 0.776 (0.629–0.923) respectively. GA levels >20.3% had 90.9% sensitivity and 96.1% specificity in detecting a 7-day average glucose ≥184 mg/dL. The AUC for GA was significantly higher than the AUC for GSP (difference between areas: 0.294, p < 0.001) and the AUC for HbA1c (difference between areas: 0.199, p < 0.01). Conclusion: Among diabetic hemodialysis patients, GA is a stronger indicator of poor glycemic control assessed with 7-day-long CGM when compared to GSP and HbA1c.

Consultants for the American Journal of Nephrology 2007

Mario Cozzolino Farhard Danesh Robert Danziger John Daugirdas Katherine Dell Luca De Nicola Janice Douglas Thomas DuBose Carolyn Ecelbarger Allison Eddy Charles Edelstein Beatrice Edwards Belkıs Erbas Ronald Falk Ken Farrington Sahar Fathallah-Shaykh Murray Favus Leon Ferder Albert Ferro Michael Fischer Steven Fishbane Barry Freedman Gordon Freeman Elena Gagliardini C. Garlichs Fumitake Gejyo P. Gentilini Cheryl Gilmartin Richard Glassock Ehud Goldhammer David Goldsmith Stuart Goldstein Jennifer Gooch Laurence Greenbaum Dimitrios Grekas Hans Grosse-Wilde Mehmet Haberal Peter Hart Tomoko Hayashida Peter Heering Klaus Hocherl Radovan Hojs Susan Hou Priscilla How Reiko Inagi Ajay Israni Edwin Jackson Sara Jandeska Vanita Jassal Kevin Abbott Dale Abrahamson Adel Afifi Rajiv Agarwal Cu-Rie Ahn Maie Albader Farah Ali Ahsan Arozullah John Asplin Brad Astor Aslihan Avci Carla Avesani Mindy Banks Vinod Bansal Mary Barchman Amelia Bartholomew Amy Barton Pai David Basile F. Baud John Beltrame Carsten Bergmann Rajendra Bhimma Daniel Bichet Peter Blake Amy Bobrowski W. Kline Bolton Michael Braun Carolyn Brecklin Ellen Brooks Edward Brown Vito Campese Caterina Canavese Zemin Cao Lucio Cardoso Daniel Catanzaro Tak Mao Chan Rene Chang Julie Chao Monique Cho Yongwon Choi Nina Clark Steven Coca David Cohen Gabriel Contreras Mark Cooper Dominic Cosgrove Scott Cotler Adrian Covic Daniel Coyne