Related Experiment Video
Updated: Mar 8, 2026

A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Effects of Direct Renin Blockade on Renal & Systemic Hemodynamics and on RAAS Activity, in Weight Excess and
A J Kwakernaak1, L C Roksnoer2, H J Lambers Heerspink3
1Department of Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands.
Aim:
The combination of weight excess and hypertension significantly contributes to cardiovascular risk and progressive kidney damage. An unfavorable renal hemodynamic profile is thought to contribute to this increased risk and may be ameliorated by direct renin inhibition (DRI). The aim of this trial was to assess the effect of DRI on renal and systemic hemodynamics and on RAAS activity, in men with weight excess and hypertension.
Methods:
A randomized, double-blind, cross-over clinical trial to determine the effect of DRI (aliskiren 300 mg/day), with angiotensin converting enzyme inhibition (ACEi; ramipril 10 mg/day) as a positive control, on renal and systemic hemodynamics, and on RAAS activity (n = 15).
Results:
Mean (SEM) Glomerular filtration rate (101 (5) mL/min/1.73m2) remained unaffected by DRI or ACEi. Effective renal plasma flow (ERPF; 301 (14) mL/min/1.73m2) was increased in response to DRI (320 (14) mL/min/1.73m2, P = 0.012) and ACEi (317 (15) mL/min/1.73m2, P = 0.045). Filtration fraction (FF; 34 (0.8)%) was reduced by DRI only (32 (0.7)%, P = 0.044). Mean arterial pressure (109 (2) mmHg) was reduced by DRI (101 (2) mmHg, P = 0.008) and ACEi (103 (3) mmHg, P = 0.037). RAAS activity was reduced by DRI and ACEi. Albuminuria (20 [9-42] mg/d) was reduced by DRI only (12 [5-28] mg/d, P = 0.030).
Conclusions:
In men with weight excess and hypertension, DRI and ACEi improved renal and systemic hemodynamics. Both DRI and ACEi reduced RAAS activity. Thus, DRI provides effective treatment in weight excess and hypertension.
Trial Registration:
Dutch trial register, registration number: 2532 www.trialregister.nl.
Related Concept Videos
Antihypertensive Drugs: Direct Renin Inhibitors
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Drugs: Angiotensin II Receptor Blockers
Hormonal Regulation
Hypertension II: Pathophysiology

