The effect of the triple renin-angiotensin-aldosterone system blockade on urinary protein excretion in patients with non-diabetic chronic nephropathy

Abstract

Background Many patients chronically treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers show a slow but a steady return of plasma aldosterone levels to baseline values, i.e. “aldosterone escape” an effect which could interfere with both their antihypertensive and target organ protective efficacy. To avoid this effect aldosterone antagonist could be added and such combined therapy has already been found to be effective and safe in patients with diabetic nephropathy. There is however a paucity of data on the effectiveness and safety of a triple blockade of the renin-angiotensin-aldosterone system.
Material and methods 10 patients with non-diabetic chronic nephropathy with sub-nephrotic range of proteinuria treated with an converting enzyme inhibitor received in addition losartan (50 mg daily) for 6 weeks and for another 6 weeks both losartan and spironolactone (25 mg daily). Blood pressure, urine protein and creatinine, plasma sodium, potassium, creatinine, renin and aldosterone concentrations were measured at all stages of the study.
Results There was a trend for the blood pressure and proteinuria to decrease after the addition of both losartan and spironolactone and there was a significant decrease of these both parameters when the triple therapy was compared to an converting enzyme inhibitor alone. The decrease of blood pressure and proteinuria after losartan was tightly correlated but the same relation was not observed after spironolactone was added.
Conclusions Treatment with triple blockade of RAAS in patients with persistent, non-nephrotic proteinuria decreases protein excretion significantly. This renoprotective effect seems to be depended on a reduction of blood pressure.