Attenuation of Cardiac Effects of Arteriovenous Fistula Creation With Losartan

Study Design: This is a prospective double blind placebo control 2 arm, randomized (1:1) parallel group study in patients with near end stage renal failure who require creation of an arteriovenous fistula for future haemodialysis. Enrolment will be over a period of 12 months. The blinded phase will be for 3 months. The study design is summarized in Appendix 1. The study consists of a screening phase, a randomization phase and a treatment phase.

Patients will be randomized into 2 groups:

• Group 1 Losartan (50mg daily blinded) and 25 mg of atenolol
• Group 2 Placebo (blinded) and 25 mg of atenolol

Patients: Patients must comply with specified inclusion and exclusion criteria. The number of patients used will be sufficient to show a 15% difference in the left ventricular mass (LVM) between the two groups

Study Endpoints: The primary endpoint is the between group difference in LVM from baseline to 1 month.

Statistical Considerations: The analysis will be based upon an 'ANCOVA'-type linear regression model that includes baseline LVM and treatment group as explanatory variables, and final LVM as the outcome variable.

Inclusion criteria

• Diagnosis of CKD at near-end stage renal failure (CKD Stage IV) ( eGFR = 15-30 mls/min).
• Age >18 years of age and <85 years of age.
• Males and post-menopausal, sterile women. Non-pregnant pre-menopausal women should be on adequate contraception and have no intention of becoming pregnant during the duration of the study.
• At baseline TTE LVEF>45%
• Willing and able to give informed consent.

Exclusion criteria

• Serum potassium level of more than 5.5 mmol/L
• Acute myocardial infarction or cerebrovascular accident in the previous 6 months.
• Severe uncontrolled hypertension (diastolic BP >100mmHg or systolic BP >160 mmHg)
• Evidence or suspicion of renovascular disease.
• Atrial fibrillation
• Evidence or suspicion of collagen disease, cancer, psychiatric disorder that interferes with patient compliance, drug or alcohol abuse, pregnancy, breast feeding and ineffective contraception.