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

Abstract

Dual renin-angiotensin-aldosterone blockade (dRAASb) is purposed in the prevention of the cardiorenal syndrome (CRS). However, all attempts with dRAASb even in patients with moderate impaired chronic kidney disease (CKD) were terminated due to the typical severe adverse events (SAE), e. g., hyperkalemia and rise of serum creatinine. The aim of our study with the direct renin inhibitor aliskiren was to evaluate the effect of dRAASb with a washout phase in patients with severely advanced CKD. We have studied 45 patients (G3b to 4, A2 and >A3; median glomerular filtration rate (GFR) CKD-EPI 31 (23-40) ml/min per 1.73 m² BSA (body surface area), albumin-creatinine-ratio in urine (UACR) (0.413 (0.164 to 1.39) g/g) and proteinuria (0.5 (0.2 to 0.9) g/l) before, with and without aliskiren (150 respectively 300 mg per day) added to an angiotensin-converting enzyme inhibitor (ACEi) or an AT1-receptor blocker (ARB) over 4 ½ years. The dRAASb with aliskiren showed a significant decrease of proteinuria (0.5 to 0.38 g/l), especially in patients with an UACR≥350 mg/g and in the subgroup analysis e. g., in patients with diabetes, but proteinuria increased in the washout phase again. The blood pressure (130/80 mm Hg), serum potassium (4.9 to 5.0 mmol/l) and GFR remained nearly constant (31 to 29.5 ml/min per 1.73 m BSA). A more than 30% increase in serum creatinine was associated with an UACR>300 mg/g. The dRAASb has beneficial effects on proteinuria and is safe in patients with severely advanced CKD. However, in patients with high UACR (>300 mg/g) raise of creatinine and potassium have to be controlled.

Antifibrotic Roles of RAAS Blockers: Update

“…This combination therapy might reduce proteinuria to a great extent. However, further subgroup analysis revealed that dual blockade of the renin-angiotensin-aldosterone system with aliskiren and ARB did not improve the hard renal endpoints, so it should not be recommended in CKD patients (Parving et al 2012;Rasche et al 2018).…”