[Frontiers in Bioscience 16, 1364-1387, January 1, 2011]

Risk factors and metabolic mechanisms in the pathogenesis of uraemic cardiac disease

Sunil Bhandari

Department of Renal Medicine, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, Kingston-upon-Hull, United Kingdom

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Pathophysiology of cardiac failure
4. What factors are implicated in uraemic cardiac disease?
4.1. Oxidative stress
4.2. Inflammation
4.3. Vitamin D deficiency and calcium phosphate metabolism
4.4. Carnitine deficiency
4.5. Anaemia and iron deficiency
4.6. Proteinuria and albuminuria
4.7. Homocysteine and hyperuricaemia
4.8. Lipids
4.9. Left ventricular hypertrophy (LVH) and metabolic changes
4.10. Insulin resistance and glycaemic control
5. Treatment options for uraemic heart disease
5.1. Established treatments
5.2. Other treatments in heart failure and their effect on renal function
5.3. Renal specific therapies
5.4. Future Targets- the metabolic pathways to reduce uraemic heart disease.
6. Perspective
7. Acknowledgements
8. References

1. ABSTRACT

Chronic kidney disease has been increasingly recognized as a risk factor for incident heart failure. Despite advances in chronic heart failure treatment, the prognosis remains poor. The annual mortality from all cardiovascular causes in the end stage renal disease population is significantly higher than the general population, accounting for more than half of all deaths in this group. The mechanisms underlying the enhanced susceptibility to myocardial ischemia in chronic kidney disease are not well defined. Traditional cardiovascular risk factors, although common in chronic kidney disease, do not exert the same impact as in the general population. The presence of "renal-specific" non-traditional risk factors including endothelial dysfunction, inflammation, oxidative stress, anaemia, proteinuria and changes in vitamin D metabolism (encompassing the compex interactions of calcium and phosphate metabolism, hyperparathyroidism and vascular calcification) play an important role in cardiovascular disease progression. An increased understanding of the array of metabolic changes/adaptations occurring in uraemic heart disease have allowed one to consider optimal management strategies and to develop new strategies for future management of uraemic heart disease.