Oxidative Stress and Inflammation in Hemodialysis Patients

Spittle, Margaret; Hoenich, Nicholas A.; Handelman, Garry J.; Adhikarla, Rohini; Homel, Peter; Levin, Nathan W.

doi:10.1007/978-94-017-1848-6_5

Cited by 35 publications

(39 citation statements)

References 22 publications

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“…Elevated NO levels in CRF patients, which significantly decreased after dialysis, and evidence for production of oxygen free radicals during HD have been reported. 25,26,27 The present study showed increased levels of FFAs, TG, TC and decreased HDL-C and Ph-lipids in predialysis samples as a consequence of carnitine deficiency with no significant changes after dialysis. After L-carnitine supplementation the FFAs, TC and HDL-C returned to control levels while TG and Ph-lipids continued to be significantly different from controls.…”

Section: Discussionsupporting

confidence: 50%

Dyslipidemia, Oxidative Stress and Cardiac Dysfunction in Children with Chronic Renal Failure: Effects of L-Carnitine Supplementation

2003

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Background: Secondary carnitine deficiency may develop in chronic renal failure (CRF) patients undergoing longterm hemodialysis (HD), with a resulting higher incidence of cardiovascular diseases, dyslipidemia and oxidative stress. We studied the efficacy of 12 months of L-carnitine supplementation on the amelioration of dyslipidemia, oxidative stress and cardiac dysfunction in 24 CRF children undergoing long-term HD compared with 24 age-and sex-matched controls. Methods: Plasma samples were analyzed spectrophotometerically before and after dialysis sessions and after 2-month supplementation with oral L-carnitine (50 mg/kg/day) for free carnitine (FC), the lipid profile, and oxidative stress markers. Echocardiography the day following dialysis measured cardiac diameters, wall thicknesses, left ventricular mass index (Ml), end diastole and systole volume indices and functions. Results: The pre-dialysis FC concentration was substantially lower than controls and decreased significantly at the end of the dialysis session. Pre-and post-dialysis plasma levels of free fatty acids (FFAs), trigyleride (TG), total cholesterol (TC) and oxidative stress markers significantly increased while high-density lipoprotein cholesterol (HDL-C) and phospholipids significantly decreased compared to controls. Echocardiography detected a significant increase in cardiac diameters and thickness, and systolic and diastolic cardiac dysfunction. After L-carnitine supplementation, plasma levels of FC increased to normal levels. FFAs, TC and HDL-C returned to control levels while TG, phospholipids, and the oxidative stress markers decreased but remained significantly higher than controls. There was a significant decrease in cardiac diameters and an increase in left ventricular diastolic function (E/A ratio), but no correlation between FC levels and echocardiographic parameters. Pre-dialysis, post-dialysis and after treatment, plasma FC level showed a significant positive correlation with HDL-C and phospholipids and a significant negative correlation with each of oxidative stress markers, FFAs, TG and TC. On the other hand, FFAs showed a significant positive correlation with TG, TC, DC, NO and a significant negative correlation with HDL-C and phospholipids. Conclusion: This study demonstrates that CRF children under regular HD suffer from a decrease in the level of plasma FC, dyslipidemia, oxidative stress, and an increase in cardiac diameters and thickness with impairment of cardiac functions. Oral L-carnitine supplementation at a dose of 50 mg/kg for 2 months can increase plasma FC level, improve dyslipidemia, decrease oxidative stress with reduction of cardiac diameters and increase in diastolic function.

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Section: Discussionsupporting

confidence: 50%

Dyslipidemia, Oxidative Stress and Cardiac Dysfunction in Children with Chronic Renal Failure: Effects of L-Carnitine Supplementation

2003

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“…In our study, of the multiple free radical lipid oxidation products monitored, only 9-HETE and F 2 -Isoprostane levels were significantly associated with the presence of CAD, even after adjustment for Framingham risk score and CRP. Remarkably, this association was observed despite multiple corrections for known cardiac risk factors, since prior studies demonstrate levels of F 2 -Isoprostane are elevated in conditions like smoking and hyperlipidemia [35][36][37]. Further studies focusing on interval changes and links to outcomes with F 2 -Isoprostane and 9-HETE are warranted.…”

Section: Discussionmentioning

confidence: 86%

Systemic elevations of free radical oxidation products of arachidonic acid are associated with angiographic evidence of coronary artery disease

Shishehbor

Zhang

Medina

et al. 2006

Free Radical Biology and Medicine

116

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Oxidant stress is widely believed to participate in cardiovascular disease pathogenesis. However, progress in defining appropriate systemic anti-oxidant targetted therapies has been hindered by uncertainty in defining clinically relevant systemic oxidant stress measures. In a case control study, 50 subjects with CAD (> 50% stenosis in one or more major coronary vessels) and 54 without CAD (< 30% stenosis in all major coronary vessels) were tested. Plasma was isolated and stored under conditions designed to prevent artificial lipid peroxidation. Systemic levels of multiple (n=9) specific fatty acid oxidation products including individual hydroxy-octadecadienoic acids (HODEs), hydroxy-eicosatetraenoic acids (HETEs), and F 2 -Isoprostanes, were simultaneously measured by high performance liquid chromatography (HPLC) with on-line tandem mass spectrometry, along with traditional risk factors and C-reactive protein (CRP) levels. Of the markers monitored, only 9-HETE and F 2 -Isoprostanes, both products of free radical-mediated arachidonic acid oxidation, were significantly elevated in patients with angiographically defined CAD (9-HETE, 8.7 ± 4 vs. 6.8 ± 4 umol/mol arachidonate, p = 0.011; and F 2 -Isoprostanes, 9.4 ± 5 vs. 6.2 ± 3umol/mol arachidonate, p < 0.001). In multivariable analyses with simultaneous adjustment for Framingham Risk Score and C-reactive protein, 9-HETE (4 th quartile OR=4.8, 95% CI=1.3 to 17.1; P = 0.016) and F 2 -Isoprostanes (4 th quartile OR=9.7, 95% CI=2.56 to 36.9; P < 0.001) remained strong and independent predictors of CAD risk. Systemic levels of 9-HETE and F 2 -Isoprostanes are independently associated with angiographic evidence of CAD and appear superior to other specific oxidation products of arachidonic and linoleic acids as predictors of the presence of angiographically evident coronary artery disease.

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“…Furthermore, it has been shown that there is a parallel increase in oxidative stress with increasingly longer durations of HD sessions. 28 Spittle et al 29 have shown a higher level of F 2 -Isoprostane, a marker of oxidative stress, in patients undergoing HD. We know from earlier studies that plasma selenium is reduced and there is significant deficiency in glutathione peroxidise scavenging system concentrations in patients on HD.…”

Section: Oxidative Stress: What Is It?mentioning

confidence: 99%

Oxidative stress in renal dysfunction: mechanisms, clinical sequelae and therapeutic options

et al. 2009

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Oxidative stress has been increasingly linked to the high incidence of cardiovascular events in patients with chronic kidney disease (CKD), especially as traditional cardiovascular risk factors seem to not be able to account for the huge cardiovascular morbidity and mortality in this population group. Oxidative stress is increased in patients with renal impairment as a result of increased oxidant activity and reduced antioxidant capacity, and this is increased in a graded manner with increasing renal dysfunction. Inflammation, which is also present in CKD, further amplifies the oxidant generation process. The two clinical sequelae of oxidative stress are endothelial dysfunction and left ventricular hypertrophy, which have adverse cardiovascular consequences. With our new understanding of oxidative stress, it is now important to assess treatment options that reduce it in the hope that they reverse endothelial dysfunction and left ventricular hypertrophy and the clinical sequelae of these abnormalities.

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Oxidative Stress and Inflammation in Hemodialysis Patients

Cited by 35 publications

References 22 publications

Dyslipidemia, Oxidative Stress and Cardiac Dysfunction in Children with Chronic Renal Failure: Effects of L-Carnitine Supplementation

Dyslipidemia, Oxidative Stress and Cardiac Dysfunction in Children with Chronic Renal Failure: Effects of L-Carnitine Supplementation

Systemic elevations of free radical oxidation products of arachidonic acid are associated with angiographic evidence of coronary artery disease

Oxidative stress in renal dysfunction: mechanisms, clinical sequelae and therapeutic options

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