Efficacy of add-on therapy of aliskiren to an angiotensin II receptor blocker on renal outcomes in advanced-stage chronic kidney disease: a prospective, randomized, open-label study.

Background: Combination therapy of aliskiren and an angiotensin II receptor blocker (ARB) has been reported to be effective for reducing the level of proteinuria. However, it remains unclear whether this combination therapy contributes to suppression of kidney disease progression. The aim of this study was to investigate the effect of aliskiren on hard renal endpoints, when added to an ARB, in patients with advanced chronic kidney disease (CKD).

Methods: The study design was a prospective, randomized open-label design. 83 CKD patients (52 men and 31 women) were enrolled and assigned randomly to an aliskiren add-on group (n = 42) or control group (n = 41). Entry criteria included elevated serum creatinine ≥ 1.5 mg/dl, urine protein excretion (≥ 1+ on urine dipstick test), and hypertension. All participants were treated with an ARB. The follow-up period was 12 months. 12 participants were withdrawn during the study period and the study was terminated in January 2012 as a consequence of the results of the interim analysis of the ALTITUDE study.

Results: Nine patients in the aliskiren group and seven patients in the control group started dialysis. Doubling of the serum creatinine level occurred in one patient in the control group. A Cox proportional hazards test showed that dual blockade of the renin-angiotensin-aldosterone system with aliskiren and ARB was not associated with improvement in hard renal endpoints.

Conclusion: We conclude that aliskiren add-on therapy to an ARB may not give any benefit and, therefore, should not be recommended in CKD patients.