Dual RAAS Blockade with Aliskiren in Patients with Severely Impaired Chronic Kidney Disease

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Dual renin-angiotensin-aldosterone blockade (dRAASb) aims to prevent cardiorenal syndrome (CRS).
• Previous dRAASb attempts in moderate chronic kidney disease (CKD) were halted due to severe adverse events like hyperkalemia and elevated creatinine.
• Advanced CKD patients require careful consideration for dRAASb therapy.

Purpose of the Study:

• To evaluate the safety and efficacy of dRAASb using aliskiren in patients with advanced CKD.
• To assess the impact of dRAASb on proteinuria, blood pressure, and renal function.
• To investigate adverse events associated with dRAASb in this specific patient population.

Main Methods:

• A study involving 45 patients with advanced CKD (GFR 31 ml/min/1.73 m² BSA).
• Patients received aliskiren (150 or 300 mg/day) added to ACEi or ARB therapy over 4.5 years.
• Measurements included proteinuria, urine albumin-creatinine ratio (UACR), serum creatinine, potassium, GFR, and blood pressure, with a washout phase included.

Main Results:

• dRAASb with aliskiren significantly decreased proteinuria, particularly in patients with UACR ≥ 350 mg/g and in diabetic subgroups.
• Proteinuria levels increased again during the washout phase.
• Blood pressure, serum potassium, and GFR remained stable; however, a >30% rise in serum creatinine was linked to UACR > 300 mg/g.

Conclusions:

• dRAASb with aliskiren demonstrates beneficial effects on proteinuria and is safe for patients with advanced CKD.
• Careful monitoring for increases in creatinine and potassium is essential in patients with high UACR (>300 mg/g).
• This approach offers a potential strategy for managing cardiorenal complications in severe CKD.