RAS Quantification in Patients With Aliskiren or Candesartan
Status:
Completed
Trial end date:
2016-02-01
Target enrollment:
Participant gender:
Summary
Forced blockade of the renin-angiotensin-system (RAS) by using direct renin inhibition (DRI)
has long been propagated to effectuate beneficial outcomes. However, recent large clinical
trials have outlined harmful effects for DRI in combination with other forms of RAS blockade.
To date, information regarding DRI as RAS-blocking monotherapy is very limited. Furthermore,
it remains to be elucidated how DRI and angiotensin receptor blockers affect the so-called
'classical' and 'alternative' RAS molecularly. As components of the 'alternative' RAS (e.g.
Ang 1-7) have moved into research focus, it would be of importance to determine angiotensin
regulation with medical RAS blockade.
In this prospective, single-center randomized trial over 10 weeks, 24 patients with chronic
kidney disease (CKD) stage III-IV (eGFR 15-59 ml/min) will be randomized to take either
aliskiren (up to 300 mg per day) or candesartan (up to 16 mg per day) after a two week run-in
phase where all RAS-blockers are eliminated. The investigators will then employ a novel mass
spectrometry-based quantification method (after run-in and 10 weeks) to capture the
concentrations of ten different angiotensin peptides (including angiotensin I and II,
angiotensin 1-7 and angiotensin 1-5).
The investigators hypothesize that significant differences exist between angiotensin levels
in CKD patients with DRI compared to angiotensin receptor blockers. Specifically, the
investigators expect to determine the regulation of the alternative RAS represented by
angiotensin 1-7 with proximal versus distal blockade of the system.
Our data might contribute to a more profound understanding of results from registries and
clinical trials beyond the clinical effects of RAS blockade. Further, the study's results
might help to individualize and optimize RAS-blocking therapy strategies in CKD patients.