Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis

Genes, Fibrinolysis and Endothelial Dysfunction- Dialysis Aim 2

Little is known about how some drugs affect inflammation or clotting factors in people receiving hemodialysis. It is not yet known if these drugs help prevent heart damage as they do in people not undergoing hemodialysis or whether they could increase the risk of heart problems. The purpose of the study is to measure certain chemicals in the blood and see how those chemicals may change during hemodialysis when certain drugs are given.

• Cardiovascular disease in the leading cause of death in patients with chronic kidney disease undergoing hemodialysis.
• Traditional risk factors do not adequately predict cardiovascular morbidity and mortality in patients with chronic kidney disease.
• Increased oxidative stress, inflammation and impaired fibrinolysis contribute to cardiovascular risk in chronic kidney disease patients undergoing hemodialysis.
• Activation of the renin-angiotensin-aldosterone system(RAAS) may contribute to oxidative stress and inflammation in individuals with chronic kidney disease
• Activation of the kallikrein-kinin system during hemodialysis may increase fibrinolysis but may also contribute to inflammation in chronic kidney disease
• Despite data from clinical trials demonstrating that ARBs and ACE inhibitors decrease cardiovascular mortality, delay progression to cardiovascular disease and decrease the incidence of diabetes in the general population little is known about the impact of these agents on cardiovascular morbidity and mortality in patients with end- stage renal disease (ESRD) undergoing hemodialysis
• Angiotensin-converting enzyme(ACE) inhibitors and angiotensin receptor blockers (ARB)S differ in their mechanisms of action and their effects on inflammatory biomarkers

Inclusion Criteria:

• Age 18 years or older
• On thrice-weekly chronic hemodialysis for at least 6 months
• Clinically stable, adequately dialyzed (single-pool Kt/V> 1.2) thrice weekly, with polysulphone membrane for at least 3 consecutive months prior to study

Exclusion Criteria:

• Body mass index > 35 mg/kg
• History of functional transplant less than 6 months prior to study
• Use of anti-inflammatory medications other than aspirin < 325 mg/d
• History of active connective tissue disease
• History of acute infectious disease within one month prior to study
• AIDS (HIV seropositivity is not an exclusion criteria)
• History of myocardial infarction or cerebrovascular event within 3 months
• Advanced liver disease
• Gastrointestinal dysfunction requiring parental nutrition
• Active malignancy excluding basal cell carcinoma of the skin
• History of ACE inhibitor-associated cough or angioedema
• Ejection fraction less than 40%
• Inability to discontinue ACE inhibitor or ARB
• Predialysis potassium repeatedly higher than 5.5 mmol/L (confirmed on a repeated blood draw)
• Anticipated live donor kidney transplant
• Use of vitamin E >60 IU/d or vitamin C >500 mg/d
• Pregnancy, breast-feeding or child-bearing potential
• History of poor adherence to hemodialysis or medical regimen
• Inability to provide consent