NCT00528385

Optimalization of Nephroprotection Using Agents Inhibiting Renin-Angiotensin-Aldosterone System

Influence of Adding Aldosterone Receptor Blocker to Dual Renin-Angiotensin-Aldosterone System Blockade on Proteinuria

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: —
• Sponsor: Medical University of Gdansk · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

The main purpose of the study is find whether the addition of aldosterone antagonist, spironolactone to dual renin-angiotensin-aldosterone system blockade involving angiotensin converting enzyme inhibitor and AT-1 angiotensin II receptor blocker leads to the reduction of proteinuria, main prognostic marker of chronic kidney disease progression.

Detailed description

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney diseases (CKD), and inhibition of the RAAS with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) may retard CKD progression. Dual pharmacological blockade of the RAAS with ACEI and ARB is recommended as a standard renoprotective management at least in patients with nondiabetic proteinuric CKD. However, neither ACEI nor ARB, even in high doses or in concomitant usage, abrogate the progression of CKD completely. Innovative approaches are needed to keep patients with CKD off dialysis. Additional blockade of the aldosterone pathway may prove to be such beneficial therapeutic concept.Aldosterone, a final effector of RAAS plays a significant role in the pathogenesis of CKD independently of angiotensin II through direct cellular action. This includes promoting an inflammatory response, endothelial dysfunction, and fibrosis by increasing plasminogen activator inhibitor (PAI-1) and transforming growth factor beta-1 (TGF-beta-1) expression and stimulation reactive oxygen species.A number of observations suggest nongenomic vasoconstrictor action of aldosterone leading to raise arterial and glomerular capillary pressure.Given these facts additional administration of aldosterone antagonist to combination treatment with ACEI and ARB, so called triple RAAS blockade may provide additional renal protection. To shed more light on this issue, we performed a randomised open controlled study to evaluate the influence of triple RAAS therapy on surrogate markers of kidney injury, i.e. proteinuria, markers of tubular involvement and kidney fibrosis.

Conditions

• Chronic Kidney Disease
• Proteinuria

Interventions

Type	Name	Description
DRUG	Spironolactone (Spironol) 25 mg	In the 8-weeks run-in period ACEI, cilazapril (5 mg), telmisartan (80 mg) and hydrochlorotiazyd (12.5 mg) were administered to achieve the target blood pressure below 130/80 mmHg. Next, they were randomly assigned to add (or not) 25 mg of spironolactone in two active treatment periods lasting 8 weeks each.

Timeline

• Start date: 2005-03-01
• First posted: 2007-09-12
• Last updated: 2007-09-12