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Ionut Nistor, Johan De Sutter, Christiane Drechsler, David Goldsmith, Maria Jose Soler, Charles Tomson, Andrzej Wiecek, Mihaela-Dora Donciu, Davide Bolignano, Wim Van Biesen, Adrian Covic
The presumed superiority of renin-angiotensin-aldosterone system (RAAS)-blocking agents over other antihypertensive agents in patients with diabetes to delay development of end-stage kidney disease (ESKD) has recently been challenged. In addition, there is ongoing uncertainty whether RAAS-blocking agents reduce mortality and/or delay ESKD in patients with diabetes and chronic kidney disease (CKD) stages 3-5. In this subgroup, there might be an expedited need for renal replacement therapy (RRT) when RAAS-blocking agents are used...
January 1, 2018: Nephrology, Dialysis, Transplantation
Anjana Bali, Nirmal Singh, Amteshwar Singh Jaggi
Apart from the well-documented role of the renin-angiotensin-aldosterone system (RAAS) in regulating the blood pressure and other related parameters, its role in modulating different physiological/pathological functions, including pain, has also been described. Like its dual role in regulating stress-related anxiety and cognitive functions, its dual role has also been documented in pain modulation in different disease states. Drugs blocking the RAAS activation, viz., renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, AT(1) receptor antagonists and aldosterone antagonists, have been shown to produce beneficial effects in migraine and neuropathic and nociceptive pain...
December 2014: Journal of the Renin-angiotensin-aldosterone System: JRAAS
Iwona Zaporowska-Stachowiak, Karolina Hoffmann, Wiesław Bryl, Andrzej Minczykowski
There has been enormous progress in antihypertensive therapy over the last few decades. However, the management of arterial hypertension is still insufficient and more efforts are needed to improve both non-pharmacological and pharmacological treatment of this widely prevalent disease. Renin-angiotensin-aldosterone system (RAAS) inhibition is crucial both for blood pressure (BP) control and for prevention of organ damage or its development in patients with hypertension. Angiotensin-converting enzyme inhibitors and/or sartans block RAAS incompletely...
August 29, 2014: Archives of Medical Science: AMS
Arjan J Kwakernaak, Jan A Krikken, S Heleen Binnenmars, Folkert W Visser, Marc H Hemmelder, Arend-Jan Woittiez, Henk Groen, Gozewijn D Laverman, Gerjan Navis
BACKGROUND: Reduction of dietary sodium intake or diuretic treatment increases renin-angiotensin-aldosterone system (RAAS) blockade efficacy in non-diabetic nephropathy. We aimed to investigate the effect of sodium restriction and the diuretic hydrochlorothiazide, separately and in combination, added to RAAS blockade on residual albuminuria in patients with type 2 diabetic nephropathy. METHODS: In this multicentre, double-blind, placebo-controlled, crossover randomised trial, we included patients with type 2 diabetic nephropathy...
May 2014: Lancet Diabetes & Endocrinology
Frederik Persson, Xifeng Lu, Peter Rossing, Ingrid M Garrelds, A H Jan Danser, Hans-Henrik Parving
OBJECTIVE: Urinary levels of renin-angiotensin-aldosterone system (RAAS) components may reflect renal RAAS activity and/or the renal efficacy of RAAS inhibition. Our aim was to determine whether urinary angiotensinogen and renin are circulating RAAS-independent markers during RAAS blockade. METHODS: Urinary and plasma levels of angiotensinogen, renin, and albumin were measured in 22 patients with type 2 diabetes, hypertension, and albuminuria, during 2-month treatment periods with placebo, aliskiren, irbesartan, or their combination in random order in a crossover study...
August 2013: Journal of Hypertension
R E Maser, M J Lenhard, P Kolm, D G Edwards
AIM: The renin-angiotensin-aldosterone system (RAAS) and autonomic nervous system regulate the cardiovascular system. Blockade of the RAAS may slow the progression of end-organ damage. Direct renin inhibition offers a means for blocking the RAAS. The objective of this study was to examine the effect of direct renin inhibition on cardiovascular autonomic function. METHODS: In this double-blind, placebo-controlled trial, 60 individuals with diabetes were randomly assigned to 300 mg of aliskiren or placebo once daily for 6 weeks...
January 2013: Diabetes, Obesity & Metabolism
Matthew R Weir, Norman K Hollenberg, Giuseppe Remuzzi, Dion H Zappe, Xiangyi Meng, Hans-Henrik Parving
OBJECTIVE: In patients with type 2 diabetes mellitus (T2DM), blocking of the renin-angiotensin-aldosterone system (RAAS) has demonstrated efficacy in lowering blood pressure (BP) and urinary albumin excretion rate (UAER). Nonetheless, not all patients successfully respond to RAAS blockade with a reduction in BP and UAER. METHODS: This secondary analysis of a double-blind study of 391 patients with T2DM assessed the importance of using higher doses of the RAAS blocker valsartan to improve the BP and UAER response in patients initially identified as prompt or delayed responders...
October 2011: Journal of Hypertension
Henry Krum, Barry Massie, William T Abraham, Kenneth Dickstein, Lars Kober, John J V McMurray, Ashkay Desai, Claudio Gimpelewicz, Albert Kandra, Bernard Reimund, Henning Rattunde, Juergen Armbrecht
The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo...
January 2011: European Journal of Heart Failure
George L Bakris
Dual renin-angiotensin aldosterone (RAAS) blockade is associated with higher risk of hyperkalemia and has not been shown, in any outcome trial of validated renal end points, that is, doubling of creatinine, time to dialysis, or death, to be superior over other approaches. It shows promise in advanced proteinuric nephropathy for additional proteinuria reduction. Whether this additional proteinuria reduction translates into meaningful outcomes of chronic kidney disease (CKD) is unknown, as proteinuria change is not a validated surrogate end point...
September 2010: Kidney International
M Dalla Vestra, N Simioni, A Masiero
The importance of renin-angiotensin aldosterone system (RAAS) in cardiovascular and renal diseases has long ago been recognized. However despite the availability of many effective drugs, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, RAAS blockade is incomplete in several patients with consequent uncontrolled high blood pressure and not efficacy cardiovascular and renal protection. Aliskiren is a new renin inhibitor that block the RAAS at its origin. Recent studies suggest that Aliskiren reduces blood pressure, inhibits plasma renin activity and attenuates renal damage in diabetic patients with nephropathy...
December 2009: Minerva Endocrinologica
Giuseppe Derosa, Ilaria Ferrari, Arrigo F G Cicero
Blood pressure (BP) is one of the most important and common vascular risk factors but it is often poorly controlled. Inhibition of the renin-angiotensin-aldosterone system (RAAS) provides beneficial effects in hypertensives. The association of low-dosed diuretics in combination with RAAS blocking agents allows maximum benefit from potassium depletion and control of compensatory increase in renin secretion, so increasing the efficacy and safety of RAAS blockers. Irbesartan is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy...
April 2009: Current Vascular Pharmacology
K J Schjoedt, H P Hansen, L Tarnow, P Rossing, H-H Parving
AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin-angiotensin-aldosterone system (RAAS) with an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in microalbuminuric type 1 diabetic patients on progression of microalbuminuria and development of DN...
June 2008: Diabetologia
Panagiotis C Stafylas, Pantelis A Sarafidis, Dimitrios M Grekas, Anastasios N Lasaridis
The aim of this study was to estimate the cost-effectiveness of renin-angiotensin-aldosterone system blockers in patients with diabetic nephropathy. A cost-effectiveness analysis was performed based on a meta-analysis of studies investigating the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) as part of a treatment regimen on the incidence of end-stage renal disease (ESRD) in patients with diabetic nephropathy. The primary outcome was the cost to prevent 1 patient from developing ESRD...
October 2007: Journal of Clinical Hypertension
James L Pool, Roland E Schmieder, Michel Azizi, Jean-Claude Aldigier, Andrzej Januszewicz, Walter Zidek, Yanntong Chiang, Andrew Satlin
BACKGROUND: By blocking the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step, renin inhibition may provide improved RAAS suppression. We investigated the blood pressure (BP)-lowering effects of the oral direct renin inhibitor aliskiren, alone or in combination with the angiotensin receptor blocker valsartan. METHODS: In this multicenter, randomized, placebo-controlled, 8-week trial, 1123 patients with mild-to-moderate hypertension underwent a 3 to 4 week single-blind placebo run-in and were then randomized in a modified factorial study design to receive once-daily, double-blind oral treatment with placebo, aliskiren monotherapy (75, 150, or 300 mg), valsartan monotherapy (80, 160, or 320 mg), aliskiren and valsartan in combination, or valsartan/hydrochlorothiazide (160/12...
January 2007: American Journal of Hypertension
Rajiv Agarwal, Muralidhar Acharya, Jin Tian, Richard L Hippensteel, Joel Z Melnick, Ping Qiu, Laura Williams, Daniel Batlle
BACKGROUND: Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients. METHODS: In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral paricalcitol (N= 107, mean dose 9...
December 2005: Kidney International
Roger A Rodby
BACKGROUND: Diabetes is the most common cause of end-stage renal disease (ESRD)-kidney failure to the point of requiring dialysis or a kidney transplant. representing 45% of all new patients enrolling into ESRD programs. Approximately 400,000 patients in the United States have ESRD, and this number has doubled over the decade from 1991-2001. Dialysis is a very expensive modality costing more than 50,000 dollars per patient per year. Total medical spending for the 400,000 patients with ESRD cost 22...
September 2004: Journal of Managed Care Pharmacy: JMCP
P S Sever, C L Chang
INTRODUCTION: Marked heterogeneity characterises blood pressure (BP)responses to antihypertensive drugs. The efficacy of drugs acting on the renin-angiotensin-aldosterone system(RAAS) is predicted (albeit weakly) by plasma renin activity (PRA) and it has been assumed that, within individuals, there would be concordance in efficacy between drugs acting at different sites to block the RAAS. DESIGN: The present study was a randomised, double-blind,two-way, crossover study designed to evaluate intra-individual BP responses to an angiotensin II AT -receptor blocker (ARB), candesartan cilexetil, and anangiotensin-converting enzyme inhibitor (ACE-I), lisinopril, and to identify potential phenotypic characteristics of patients' responses to the drugs...
March 2001: Journal of the Renin-angiotensin-aldosterone System: JRAAS
Y Lacourcière
BACKGROUND: Blockade of the renin-angiotensin-aldosterone system (RAAS) is the preferred mechanism of action for controlling hypertension in select groups of patients, including those with diabetic nephropathy and heart failure. Currently, 2 classes of drugs work by blocking the RAAS, albeit by differing mechanisms: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II angiotensin type 1 receptor blockers (ARBs). OBJECTIVE: The goal of this study was to assess the comparative efficacy and tolerability of the ARB irbesartan and the ACE inhibitor enalapril in patients > or = 65 years of age with mild to moderate hypertension (sitting diastolic blood pressure [DBP], 95 to 110 mm Hg)...
October 2000: Clinical Therapeutics
J Møller, N Møller, E Frandsen, T Wolthers, J O Jørgensen, J S Christiansen
To test if the renin-angiotensin-aldosterone system (RAAS) is involved in growth hormone (GH)-associated fluid retention, we examined the effect of GH administration in the presence or absence of RAAS blockade at different levels on body fluid homeostasis. Eight subjects were examined in a controlled, randomized double-blinded trial. During four 6-day periods they received subcutaneous GH (6 IU-m-2) or placebo injections and tablets as follows: 1) placebo and placebo, 2) GH and placebo, 3) GH and captopril, and 4) GH and spironolactone...
May 1997: American Journal of Physiology
B Pitt, P Chang, W Grossman, M Dunlay, P B Timmermans
The randomized angiotensin receptor antagonist--angiotensin converting enzyme (ACE)--Inhibitor Study (RAAS) was designed to test the hypothesis that the addition of an angiotensin II type 1 receptor blocking agent, losartan 50 mg/day, to an ACE-inhibitor, enalapril 10 mg twice a day (group 1), will be more effective than standard-dose enalapril 10 mg twice a day (group 2) or high-dose enalapril alone 20 mg twice a day (group 3), in blocking the activation of the renin angiotensin aldosterone system in patients with heart failure and left ventricular systolic dysfunction...
November 15, 1996: American Journal of Cardiology
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