Chronic Kidney Disease, Hypertension, Proteinuria
Conditions
Keywords
renin-angiotensin-system, RAS blockade
Brief 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.
Interventions
OTHERRAS blockade discontinuation
In the initial two weeks of the study, all RAS blockade will be eliminated from the subjects' antihypertensive regimen
DRUGAliskiren
DRUGCandesartan
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Chronic kidney disease stages III-IV (defined by modification of diet in renal disease (MDRD) formula) * Urinary albumin to creatinine ratio (UACR) \>300mg/g, UACR \>200mg/g if already receiving RAS blockade * Arterial hypertension
Exclusion criteria
* Age \<18 years * Diabetes mellitus type 2 (defined by WHO criteria) * Chronic kidney disease stage V (end-stage renal disease) * UACR \>3500mg/g * Severe hypertension (systolic blood pressure \>180mmHg) * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mass spectrometry RAS peptide quantification | 2 months | Quantitative RAS peptide changes determined by mass spectrometry after a 2-month treatment with aliskiren or candesartan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure | 2 months | Blood pressure reduction, determined by ambulatory blood pressure measurements at study start and end |
| Proteinuria | 2 months | Proteinuria reduction, measured by urinary albumin/creatinine ratio at study start and end |
Countries
Austria
Outcome results
None listed