The endotoxin-lipoprotein hypothesis

Rauchhaus, Mathias; Coats, Andrew J.S.; Anker, Stefan D.

doi:10.1016/s0140-6736(00)02690-8

Cited by 483 publications

(330 citation statements)

References 30 publications

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“…An alternative explanation for the inverse association between cholesterol and mortality is a true protective effect of higher lipid levels. The hypothesis championed by Rauchhaus et al (20,21) suggests that binding of lipoproteins to bacterial endotoxins may result in reduced inflammation; therefore, higher lipoprotein levels may be of benefit. Indeed, contrasting the studies by Liu et al and Iseki et al, other studies in patients who were on RRT could not account for the inverse association between total cholesterol and mortality by adjusting for surrogates of MICS (7,8).…”

Section: Discussionmentioning

confidence: 99%

Inverse Association between Lipid Levels and Mortality in Men with Chronic Kidney Disease Who Are Not Yet on Dialysis

Kövesdy

Anderson²,

Kalantar-Zadeh

2007

Journal of the American Society of Nephrology

130

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High total cholesterol is associated with lower mortality in dialysis patients, but the relationship between lipid levels and mortality in patients who have chronic kidney disease (CKD) and are not yet on dialysis is poorly described. This study examined the association between lipid levels and all-cause and cardiovascular mortality in 986 male patients (age 67.4 ؎ 10.9 yr; race 23.7% black) who had CKD and were not yet on dialysis. Associations were determined in fixed-covariate and time-dependent Cox models, before and after adjustment for components of case mix and surrogates for malnutrition-inflammation-cachexia syndrome (MICS). Lower total cholesterol quartiles were associated with higher all-cause mortality in a fixed-covariate model that was adjusted for age, race, and body mass index (hazard ratio T he association between lipid abnormalities (higher total cholesterol, LDL cholesterol, and triglycerides and lower HDL cholesterol) and increased mortality is established firmly in the general population (1,2). Contrasting with this, numerous observational studies have documented an increased mortality associated with lower total cholesterol level in patients who had chronic kidney disease (CKD) and received renal replacement therapy (RRT) (3-9). Given the high mortality rate that is experienced by patients with CKD and the preponderance of cardiovascular causes that are responsible for this (10 -12), the observed inverse association between total cholesterol and mortality in patients with CKD has become a topic of significant interest (13). Although patients with CKD who are not yet receiving RRT clearly outnumber those who are on RRT (14), there is a paucity of information about the lipid levels that are found in these patients and the outcomes that are associated with these levels. In addition, descriptive studies that have explored the association of a single baseline lipid level with various outcomes cannot account for the longitudinal variation of lipids or for therapeutic interventions that were instituted after the evaluation period but before the occurrence of an outcome. We sought to examine all-cause and cardiovascular mortality as a function of lipid levels in a historical, prospective cohort of patients who had moderate and advanced CKD and were not receiving RRT. We collected data on pertinent clinical and biochemical characteristics and therapeutic interventions longitudinally to capture temporal variations and their effects of outcomes.[ Materials and Methods Study PopulationPatients who were evaluated for management of CKD at Salem VA Medical Center (VAMC) , which utilizes data from the DOPPS study to define the factors that predict early mortality in the first 4 months after transplantation and document the benefit of predialysis care by a nephrologist who can identify and modify these risk factors.

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Section: Discussionmentioning

confidence: 99%

Inverse Association between Lipid Levels and Mortality in Men with Chronic Kidney Disease Who Are Not Yet on Dialysis

Kövesdy

Anderson²,

Kalantar-Zadeh

2007

Journal of the American Society of Nephrology

130

View full text Add to dashboard Cite

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“…These include a benefit from the better nutritional status typically seen in obese individuals, and which provides better protein and energy reserves in the face of acute illness, and a higher muscle mass with enhanced antioxidant capacity 63 and lower circulating actin and higher plasma gelsolin levels, 71 which are associated with better outcomes. Other hypothetically beneficial characteristics of obesity include a more stable hemodynamic status with mitigation of stress responses and heightened sympathetic and renin-angiotensin activity; 72 increased production of adiponectines 73 and soluble tumor necrosis factor alfa receptors 74 by adipose tissue neutralizing the adverse effects of tumor necrosis factor alfa; enhanced binding of circulating endotoxins 75 by the characteristically higher cholesterol levels seen in obesity; and sequestration of uremic toxins by adipose tissue.…”

Section: Obesity In Patients With Advanced Kidney Disease: the Need Fmentioning

confidence: 99%

Obesity and Kidney Disease: Hidden Consequences of the Epidemic

Kövesdy¹,

Furth²,

Zoccali³

2017

Nephrol Open J

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“…Endotoxin may be an important mediator of heart failure progression via activation of proinflammatory cytokines. 22) Second, statins can depress the production of CoQ10 which is a central rate-limiting constituent of the mitochondrial respiratory chain. It is therefore conceivable that CoQ10 depletion, which has been found in the myocardium from patients with heart failure, 23) may contribute to the deterioration of functional capacity of failing hearts.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin-Induced Changes in Plasma Coenzyme Q10 and Brain Natriuretic Peptide in Patients With Coronary Artery Disease

et al. 2008

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SUMMARYThe beneficial effects of statins in patients with coronary artery disease (CAD) may be balanced by concerns that statins can depress production of ubiquinone (CoQ10), which serves as a component of mitochondrial energy production and an antioxidant. Accordingly, the effects of atorvastatin (ATO)-induced changes in plasma CoQ10 on BNP and oxidative stress were investigated. In 29 patients with CAD, the plasma levels of CoQ10 and BNP and urinary excretion of 8-iso-prostaglandin F2α (8-iso-PGF) were determined before and after 3-month treatment with ATO. Ten patients had received pravastatin and 10 patients fluvastatin, while 9 patients had not received any statin before ATO. There was a linear correlation between ATO-induced changes in total cholesterol and CoQ10 (r = 0.632, P < 0.01), and an inverse correlation between ATO-induced changes in CoQ10 and BNP (r = -0.497, P < 0.01). There was no significant correlation between ATO-induced changes in CoQ10 and 8-iso-PGF. Multivariate analysis revealed that ATO-induced decreases in plasma CoQ10 were significantly associated with increasing BNP levels. In conclusion, long-term treatment with ATO might increase plasma levels of BNP in patients with CAD when it is accompanied by a greater reduction in plasma CoQ10. However, ATO-induced decreases in CoQ10 might not increase oxidative stress. (Int Heart J 2008; 49: 423-433)

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The endotoxin-lipoprotein hypothesis

Cited by 483 publications

References 30 publications

Inverse Association between Lipid Levels and Mortality in Men with Chronic Kidney Disease Who Are Not Yet on Dialysis

Inverse Association between Lipid Levels and Mortality in Men with Chronic Kidney Disease Who Are Not Yet on Dialysis

Obesity and Kidney Disease: Hidden Consequences of the Epidemic

Atorvastatin-Induced Changes in Plasma Coenzyme Q10 and Brain Natriuretic Peptide in Patients With Coronary Artery Disease

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