Aldosterone breakthrough during therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in proteinuric patients with immunoglobulin A nephropathy

Background:  We are investigating whether aldosterone breakthrough negatively impacts on the antiproteinuric effects of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARB).

Methods:  We examine the role of aldosterone breakthrough in 43 normotensive, proteinuric (0.7 ± 0.3 g/day) outpatients (aged 41.5 ± 10.9 years) with immunoglobulin A nephropathy (IgAN) accompanied by stable renal function (creatinine clearance >50 mL/min). The patients were treated with temocapril (1 mg; n = 14), losartan (12.5 mg; n = 16), or a combination therapy (n = 13) for 12 months. We prospectively evaluated blood pressure (BP), urinary protein excretion (UPE), biochemical parameters and the renin-angiotensin-aldosterone system before and after 12 months of treatment.

Results:  Although the overall plasma aldosterone concentrations values did not change after any of the treatments administered for 12 months, they eventually increased in 23 (temocapril, seven patients; losartan, eight patients; combination, seven patients) of the 43 patients (53.4%; aldosterone breakthrough), and fell in the remainder (46.6%). Blood pressure and renal function did not differ among the three groups at 12 months. In contrast, UPE was significantly higher in patients with, than without aldosterone breakthrough during temocapril and losartan administration. However, combination therapy induced a more remarkable reduction in UPE regardless of aldosterone breakthrough.

Conclusions:  A combination of ACE inhibitors and ARB in normotensive patients with IgAN produces a more profound decrease in proteinuria than either monotherapy. This additive antiproteinuric effect is not dependent on aldosterone breakthrough. Additional larger, prospective, randomized studies will be needed for general acceptance of this strategy.