The purpose of this study is to determine which combination of the tablets ramipril, irbesartan or spironolactone is best to lower protein leakage from the kidney.

Protein leak from the kidney into the urine is an indicator of kidney damage. The higher the leak, the worse the damage and the more likely the patient will lose their kidney function long term. Interventions that lower protein leak make the kidneys last longer.

There are 2 groups of medications, both blood pressure tablets, the ACEI (angiotensin converting enzyme inhibitors) and ATRB (angiotensin receptor blockers) which have shown to reduce the amount of protein leaking from the kidney and as a result lengthen the life of the kidney. There has also been evidence that using these 2 tablets in combination is better than using either one alone. In spite of these tablets, there still remain some patients that continue to leak protein in the urine.

Recently there has been evidence that the tablet spironolactone, which is a fluid tablet, also reduces protein leakage from the kidney. In this study we look at various combinations of these tablets to see which works best to lower protein leakage from the kidney.

Patients are divided into 4 groups. Each group will receive the tablet ramipril (an ACEI). In group 1, patients will be on ramipril and 2 blank tablets, group 2 will be on ramipril, irbesartan (an ATRB) and a blank tablet, group 3 will be on ramipril, spironolactone and a blank tablet and group 4 will be on ramipril, irbesartan and spironolactone. Protein leakage is measured at the beginning and after 3 months of treatment.

Inclusion Criteria:

• Proteinuria more than 1.5 g/day
• On ACEI for more than 6 months
• Serum creatinine less than 200 micromol/L with less than 20% variability in the preceeding 3 months
• Creatinine clearance more than 30 ml/min, with less than 20% variability in the preceeding 3 months

Exclusion Criteria:

• Serum potassium level more than 5 mmol/L
• Treatment with corticosteroids, NSAID or immunosuppressant medication
• Acute myocardial infarction or cerebrovascular accident in the previous 6 months
• Severe uncontrolled hypertension (diastolic > 115 mmHg or systolic BP [blood pressure] > 220 mmHg)
• Evidence or suspicion of renovascular disease, obstructive uropathy, collagen disease, cancer, drug or alcohol abuse, pregnancy, or breast feeding and ineffective contraception