Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
Status:
Terminated
Trial end date:
2012-12-01
Target enrollment:
Participant gender:
Summary
Primary Hypothesis: Aldosterone breakthrough will occur at a far lower frequency during renin
inhibition (0-10% over 9 months), alone or in combination with an ARB, compared to
conventional ARB therapy (35-45% over 9 months). The investigators hypothesize that
aldosterone breakthrough occurs due to accumulation of active precursor substances, most
notably angiotensin II, produced in response to conventional RAAS blockade with ACEinhibitors
and ARBs. The investigators believe that direct renin inhibition (DRI) should minimize this
accumulation and therefore significantly lower or possibly eliminate the breakthrough effect.
Interruption of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting
enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs), alone and in
combination, has become a leading therapy to slow the progression of chronic heart and kidney
disease. Both types of drugs inhibit the formation of aldosterone, a hormone, which has been
shown to have harmful effects on patients with chronic heart and kidney disorders. This
treatment is effective but not perfect since, even after an initial improvement, many
patients become worse over the long term. This may be due to an unexpected increase in
aldosterone, a phenomenon called "aldosterone breakthrough."
The purpose of this study is to find out whether the use of a direct renin inhibitor (DRI)
alone, or in combination with an angiotensin receptor blocker (ARB), will lessen the
occurrence of aldosterone breakthrough since direct renin inhibitors inhibit the formation of
aldosterone at a very early step. This study will compare the effectiveness of adding Diovan
(valsartan) or Tekturna (aliskiren) or a combination of Diovan and Tekturna to the usual
antihypertensive treatment. The investigators will follow blood pressure, aldosterone levels,
and urinary protein levels over 9 months to evaluate which of these therapies is most
effective for treating hypertension in patients with proteinuric kidney disease.