Sonja Radenkovic

Oxidative stress in renal anemia of hemodialysis patients is mitigated by epoetin treatment.

Background/Aims: Oxidative stress often occurs in chronic hemodialysis (HD) patients. The objective of our study was to investigate the interrelationship between oxidative stress and the degree of renal anemia. Methods: In 107 consecutive HD patients, serum concentrations of two major aldehydic lipid peroxidation (LPO) products, 4-hydroxynonenal (HNE) and malondialdehyde (MDA), and of protein carbonyls were analyzed as parameters of oxidative stress and related to the degree of renal anemia. Additionally, in 76 patients treated with epoetin long-term changes in the serum levels of aldehydic LPO products were observed. Results: In HD patients, serum levels of HNE, MDA, and protein carbonyls are increased in comparison to controls. The lower the hemoglobin, i.e. the stronger the degree of renal anemia, the higher the serum concentrations of HNE, MDA, and protein carbonyls. The HNE and MDA levels decreased during HD. Long-term studies on the correction of renal anemia by epoetin demonstrated a mitigation of oxidative stress during this therapy. During periods of 1 and 2 years, it was observed that the serum levels of HNE and MDA could be reduced. Conclusion: Chronic renal failure is connected with oxidative stress which correlates with the degree of renal anemia, and the serum levels of aldehydic LPO products could be reduced during correction of renal anemia by epoetin.

Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease

Abstract Purine nucleotide liberation and their metabolic rate of interconversion may be important in the development of hypertension and its renal consequences. In the present study, blood triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) breakdown pathway was evaluated in relation to uric acid concentration and xanthine dehydrogenase/xanthine oxidase (XDH/XO) in patients with essential hypertension, patients with chronic renal diseases on dialysis, and control individuals. The pattern of nucleotide catabolism was significantly shifted toward catabolic compounds, including ADP, AMP, and uric acid in patients on dialysis program. A significant fall of ATP was more expressed in a group of patients on dialysis program, compared with the control value (p < 0.001), while ADP and AMP were significantly increased in both groups of patients compared with control healthy individuals (p < 0.001), together with their final degradation product, uric acid (p < 0.001). The index of ATP/ADP and ATP/uric acid showed gradual significant fall in both the groups, compared with the control value (p < 0.001), near five times in a group on dialysis. Total XOD was up-regulated significantly in a group with essential hypertension, more than in a group on dialysis. The activity of XO, which dominantly contributes reactive oxygen species (ROS) production, significantly increased in dialysis group, more than in a group with essential hypertension. In conclusion, the examination of the role of circulating purine nucleotides and uric acid in pathogenesis of hypertension and possible development of renal disease, together with XO role in ROS production, may help in modulating their liberation and ROS production in slowing progression from hypertension to renal failure.

Circulating nucleic acids as possible damage-associated molecular patterns in different stages of renal failure

Chronic renal failure (CRF) is a condition associated with the risk of cardiovascular complications. Systemic inflammatory response, initiated by the pathogen-associated molecular-pattern (PAMP) molecules, exerts many similarities with the damage-associated molecular-pattern (DAMP) molecule-induced systemic response. Up to now, a number of DAMP molecules were identified. We hypothesized that the available circulating nucleic acids, acting as DAMPs, may modulate immunoinflammatory reaction in CRF. Patients with the different stages of chronic kidney disease, kidney transplantation, and patients on dialysis were included in the study. Obtained results about higher concentration of circulating ribonucleic acid (RNA), according to the stages of kidney diseases, may contribute to the hypothesis that damaged kidney tissue releases nucleic acids. Circulating RNAs expressed maximal absorbance peak at 270 nm in spectrophotometric scan analysis, which corresponded to polyC, compared to different standard samples. During in vitro conditions, by using the culture of human residential macrophages, circulating RNA isolated from patients with IV–V-stage renal diseases, patients on hemodialysis, and patients who underwent renal transplantation were able to significantly change signal transduction proteins related to inflammation and antiviral response. They significantly increased the intracellular concentration of active nuclear transcription factor nuclear factor kappa B (NF-κB), interferon regulatory factors (IRF)-3, and IRF-7 and significantly decreased melanoma differentiation-associated protein-5 (MDA-5) and p38. In this way, it seems that circulating RNA, acting as DAMP, may contribute to the mechanisms of additional inflammatory reaction, possible immune destruction, and decreased antiviral response, related to complications in kidney diseases.

9A.02: SODIUM SENSITIVE HYPERTENSION: CAN IT BE ASSESSED BY MEASURING URIC ACID LEVELS?

Objective: It was already documented, by many investigators, that hyperuricemia presents an important factor in the development of essential arterial hypertension. The goal of this study was to examine correlation between serum uric acid levels in patients with essential arterial hypertension and index of sodium sensitivity, as the main parameter of salt-sensitive hypertension. Design and method: The investigation included 236 participants of both sexes. Clinical group included 178 of participants, mean age 59 ± 18.2 years, with at least 5 years of hypertension history and preserved kidney function. They were divided into 2 subgroups according to the serum uric acid levels. Control group involved 58 healthy volunteers, who were age and sex matched with the clinic group. The levels of serum uric acid were measured spectrophotometrically. Sodium sensitivity index was assessed as the main parameter of salt sensitive hypertension. It was calculated as the difference in 24 hours sodium excretion between period of sodium rich diet (250 mmol/24 hours) and sodium lean diet (50 mmol/24 hours), divided by mean arterial pressure, measured twice respectively. Results: First clinical subgroup had 95 patients, with normal uric acid serum values (256 ± 35 &mgr;mol/l), and the second subgroup had 83 patients, with significant increase of uric acid serum values (572 ± 49 &mgr;mol/l; p < 0.01). Sodium sensitivity index in the first subgroup had normal values (0.026 ± 0.005), and in a second subgroup was significantly higher (0.078 ± 0.02; p < 0.01). We found a high positive correlation (r = 0.721, p < 0.01) between an increase in serum uric acid level and salt-sensitivity index in patients. Conclusions: Hyperuricemia and salt-sensitivity index correlate highly, therefore serum uric acid levels may be used as diagnostic parameters of salt-sensitive arterial hypertension in the population of patients with essential hypertension.

Crosstalk of inflammatory mediators and lipid parameters as early markers of renal dysfunction in stable renal transplant recipients with regard to immunosuppression

BACKGROUND Kidney transplantation is still the treatment of choice for end-stage renal disease, therefore it is important to establish all modifiable risk factors for initiation of renal dysfunction. MATERIAL/METHODS We enrolled 73 renal transplant recipients, who were more than 12 months post-renal transplant surgery, had a stable graft function, had no clinically present cardiovascular disease, and were on standard immunosuppressive therapy. The concentrations of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), CRP, lipids, and lipoproteins were measured. We used logistic regression to calculate non-adjusted, age, and multivariable-adjusted ORs and 95% confidence intervals for glomerular filtration rate, GFR <60 ml/min/1.73 m(2). RESULTS Non-adjusted OR showed that there was a significant risk of reduced GFR in patients with total cholesterol higher than 5.19 mmol/L, LDL cholesterol ≥ 4.1 mmol/L, non- HDL ≥ 4.2 mmol/L, and higher VCAM-1 concentration. After adjustment for age and in multivariable model, OR showed a significant risk for reduced GFR in patients with total cholesterol ≥ 5.2 mmol/L, LDL ≥ 4.1 mmol/L, non-HDL ≥ 4.2 mmol/L, and higher VCAM-1 concentration. HDL, triglycerides, CRP, and lipoprotein ratios did not have any significance as predictors of renal dysfunction. There were no differences in all evaluated parameters between groups in regard to immunosuppressive therapy. CONCLUSIONS Total cholesterol, LDL, non-HDL, and VCAM-1 are strong and independent predictors of renal dysfunction in stable renal transplant recipients. In contrast, HDL, CRP, triglycerides, and ICAM-1 did not seem to have any impact on renal dysfunction.

Crosstalk of Various Biomarkers That Might Provide Prompt Identification of Acute or Chronic Cardiorenal Syndromes

Introduction: Pathophysiological interaction between the heart and kidneys represents the basis for clinical entities called cardiorenal syndromes. The purpose of the study was to assess the relations between acute and chronic cardiorenal syndromes and biomarkers [advanced oxidation protein products, brain natriuretic peptide, malondialdehyde, xanthine oxidoreductase (XOD), xanthine oxidase, xanthine dehydrogenase, interleukin 8, cystatin C, plasminogen activator inhibitor-1, high-sensitive troponin T, C-reactive protein and glomerular filtration rate, measured by the Modification of Diet in Renal Disease (MDRD) formula], to hypothesize biomarkers that might provide a prompt identification of acute or chronic cardiorenal syndromes, and to distinguish acute versus chronic types of these syndromes. Methods: A total of 114 participants were enrolled in this study, i.e. 79 patients divided into subgroups of acute and chronic cardiorenal syndromes and 35 volunteers. Results: Nonadjusted odds ratio (OR) showed that there was a significant risk for acute cardiorenal syndrome with increased XOD activity (p = 0.037), elevated cystatin C concentration (p = 0.038) and MDRD (p = 0.028). Multivariable adjusted OR, on the other hand, revealed that only glomerular filtration rate measured by the MDRD formula had a significance for acute cardiorenal syndrome (p = 0.046). Nonadjusted OR showed a significant risk for chronic cardiorenal syndrome only in elderly (p = 0.002). Multivariable adjusted OR exhibited that age was the only risk factor for chronic cardiorenal syndrome (p = 0.012). Conclusion: Cystatin C, glomerular filtration rate measured by the MDRD equation and XOD were independent risk factors for acute cardiorenal syndrome, while age remained an independent risk factor for chronic cardiorenal syndrome. When comparing ORs of evaluated parameters, the highest significance for acute cardiorenal syndrome was plasma concentration of cystatin C.

Evidences for oxidative stress in essential hypertension

AimThis study explores the degree of oxidative stress in essential arterial hypertension (EAH). Even oxidative stress appears as one of several metabolic abnormalities involved in essential hypertension, it remains uncertain whether is primary or secondary. However measurement of the main oxidant may be useful in order to recognize and monitor oxidative stress.MethodsLipid peroxidation products (TBA reac tive substances) were determined in red blood cells (RBC) and serum together with markers of antioxidant status: total antioxidative capacity (AOC), catalase activity (CAT) and RBC glutathione (GSH) content in four investigated groups. The first group consisted of regularly and adequately treated hyper tensive patients without complication (regulated), patients with hyper tension and complication of some organs and organic systems were the non-regulated group. Third group were patients at the beginning of EAH (non-treated) and controls were normotensive individuals.ResultsCompared with controls, regulated and non-treated group, non-regulated hyper tensive pati ents had higher TBARS concen tration in plasma (p<0.001) and lower AOC, CAT activity without differences in GSH content.ConclusionRecent findings suggest that hyper tension is a condition followed by intensive oxidative stress and reduced antioxidant factors. Adequate and strictly controlled therapy, hygienic and diet regime and possible use of antioxidants can signi fi cantly reduce blood pressure and prevent possible complications.

PS 02-44 URIC ACID CONCENTRATION, XANTHINE OXIDASE ACTIVITY AND SALT SENSITIVITY INDEX AS PREDICTORS FOR PRIMARY ARTERIAL HYPERTENSION – WHICH ONE IS THE BEST?

Objective: The goal of the study was to measure plasma concentration of uric acid and xanthine oxidase (XO) activity and to determine index of sodium sensitivity in the group of patients with primary arterial hypertension, and to hypothesize among them, by multivariate modeling, parameters that represent best risk factors for development of primary arterial hypertension. Design and Method: We included 178 patients, mean age 59 ± 18.2 years. The patients had to have preserved kidney function, to be at least 5 years with diagnosed primary arterial hypertension, to be without a disorder manifested with uric arthropathy and without diuretic therapy for at last 6 months. Salt sensitivity index was calculated by dividing mean arterial pressure with natriuresis for 24 hours. XO activity was measured in plasma according to the liberation of uric acid by using xanthine as substrate in the absence of NADH. Uric acid serum concentration was measured spectrophotometrically. Results: Significant differences were found between groups in all evaluated parameters, acidum uricum (p = 0.002), XO activity (p = 0.002), and salt sensitivity index (p < 0.001). Non-adjusted OR showed that there was a significant risk for primary arterial hypertension with increased XO activity (OR = 1.015, p = 0.037), elevated uric acid concentration (OR = 1.058, p = 0.038), and high salt sensitivity index (OR = 1.821, p = 0.028). Comparing theses predictive values the highest significance for primary arterial hypertension was salt sensitivity index (OR = 1.821). Conclusions: Acidum uricum, XO activity, and salt sensitivity index were independent risk factors for primary arterial hypertension. Comparing OR of evaluated parameters the highest significance for hypertension had measuring salt sensitivity.