Influence of Aliskiren on Proteinuria (ALIPRES)

The Effect of Aliskiren on Proteinuria in Chronic Nondiabetic Kidney Disease: a Double Blind Cross-over Randomized Controlled Trial

To evaluate the proteinuria lowering efficacy as well as tolerability and safety of the renin inhibitor aliskiren compared with that of placebo and angiotensin converting enzyme inhibitor perindopril in patients with non-diabetic chronic renal disease.

Proteinuria is a major risk factor for progression to end-stage renal disease in both diabetic and nondiabetic nephropathies. Angiotensin II and aldosterone are the key players in the development of renal failure, either directly by promoting tissue fibrosis or indirectly through their action on glomerular hemodynamic and proteinuria. Therefore, pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) may have a beneficial impact on proteinuria and chronic kidney diseases progression. Recently, renin inhibitors, a new class of drugs that selectively inhibits angiotensin II formation at the first step of the RAAS cascade has been introduced to clinical practice. Aliskiren is the first orally bioavailable direct renin inhibitor approved for the treatment of hypertension. Blood pressure (BP)-lowering effect of aliskiren is associated with a decreased generation of angiotensin I, as it blocks its generation from angiotensinogen, by inhibiting the active enzymatic site of renin. The investigators plan this study to evaluate the short-term effects of treatment with aliskiren to those of placebo and ACEI perindopril on proteinuria.

Investigate the antiproteinuric effect of adding aldosterone antagonist, spironolactone to the combination therapy with angiotensin converting enzyme inhibitor and AT-1 receptor blocker in maximal recommended doses. reduction of proteinuria

Inclusion Criteria: age 18-65 years chronic non-diabetic proteinuric nephropathy creatinine clearance above 30 ml/min stable proteinuria above 500 mg/ 24 hours blood pressure above 125/75 mmHg and below 150/95 mmHg no steroids or other immunosuppressive treatment for a minimum of six months before the study Exclusion Criteria: unstable coronary heart disease decompensated congestive heart failure in the previous 6 months episode of malignant hypertension or stroke in the history diabetes creatinine clearance below 30 ml/min