Related Experiment Video

Updated: Apr 19, 2026

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion
08:35

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion

Published on: May 26, 2022

4.5K

Dual renin-angiotensin system blockade for nephroprotection: still under scrutiny

Giorgio Gentile, Giuseppe Remuzzi, Piero Ruggenenti

    Nephron
    |December 23, 2014
    PubMed

    Insights

    Combination therapy with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) effectively reduces proteinuria and prevents chronic kidney disease (CKD) progression. The Remission Clinic protocol shows promise for non-diabetic CKD patients.

    Area of Science:

    • Nephrology
    • Pharmacology
    • Internal Medicine

    Background:

    • Chronic kidney disease (CKD) is a major health concern, with proteinuria and structural lesions indicating disease progression.
    • Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are key treatments for CKD.
    • Combination therapy with ACEi and ARB has shown potential benefits in experimental models.

    Purpose of the Study:

    • To evaluate the efficacy of ACEi and ARB combination therapy in reducing proteinuria and preventing end-stage renal disease (ESRD) in human CKD patients.
    • To compare the effectiveness of a multidrug, individually tailored antiproteinuric treatment (Remission Clinic protocol) with ACEi/ARB monotherapy.

    Main Methods:

    • Review of experimental studies and human clinical trials, including the ONT ОнTARGET, ALTITUDE, and VA NEPHRON D studies.
    • Analysis of the Remission Clinic protocol, involving individually tailored combination therapy with maximum tolerated doses of ACEi and ARB.
    • Assessment of proteinuria reduction, prevention of structural lesions, and impact on ESRD progression.

    Main Results:

    • Experimental studies show ACEi/ARB combination therapy is more effective than monotherapy in reducing proteinuria and preventing lesions.
    • The Remission Clinic protocol demonstrated superior efficacy in reducing proteinuria and preventing ESRD compared to ACEi/ARB monotherapy, especially in non-diabetic CKD.
    • Some trials (ONTARGET, ALTITUDE) showed no additional benefit of adding ACEi or renin inhibitors to ARB monotherapy.
    • The VA NEPHRON D study indicated a trend towards reduced risk of GFR decline, ESRD, or death with combination therapy in type 2 diabetes patients, though not statistically significant due to early termination.

    Conclusions:

    • The Remission Clinic protocol is a highly effective strategy for preventing ESRD in non-diabetic proteinuric CKD.
    • Further research, such as the ongoing VALID trial, is needed to determine if this approach can be safely applied to type 2 diabetes patients.

    More Related Videos

    A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis08:21

    A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis

    Published on: October 26, 2020

    5.8K
    Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors12:03

    Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors

    Published on: June 7, 2016

    18.6K

    Related Concept Videos

    Antihypertensive Drugs: Direct Renin Inhibitors01:25

    Antihypertensive Drugs: Direct Renin Inhibitors

    The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
    1.9K
    Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

    Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

    The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
    1.5K
    Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

    Antihypertensive Drugs: Angiotensin II Receptor Blockers

    In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
    3.1K
    Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

    Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

    Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
    2.9K
    Hormonal Regulation01:33

    Hormonal Regulation

    The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
    37.5K
    Antihypertensive Drugs: Action of β1 Blockers01:17

    Antihypertensive Drugs: Action of β1 Blockers

    β1-receptors are primarily located in the heart and kidneys. In cardiac myocytes, these receptors interact with neurotransmitters released by the sympathetic nervous system during heightened activity or danger. As a result, β1-receptors get activated, initiating a series of biochemical processes. Excessive activation of beta receptors due to chronic stress can abnormally increase heart rate and contractility, resulting in high blood pressure or hypertension. To counteract this,...
    2.3K