An Issue of Dependence: Implications From the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) Trial

Riche, Daniel M.; Minor, Deborah S.; Holdiness, Amber; East, Honey E.

doi:10.1111/j.1751-7176.2008.00069.x

Cited by 8 publications

(6 citation statements)

References 15 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial [40], the combination of a DRI with an ARB was found to have a stronger organ-protective effect than ARB monotherapy, suggesting that inhibition of the increase in ARB-induced RAS activity promotes the protection of organs and tissues. As described above, the synergistic organ-protective effect of cilnidipine and an ARB may be attributable to the inhibitory effect of cilnidipine on the NA content in the renal cortex.…”

Section: Discussionmentioning

confidence: 99%

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Aritomi

Niinuma²,

Ogawa³

et al. 2011

Am J Nephrol

View full text Add to dashboard Cite

Background: Interrupting the renin-angiotensin system (RAS) with an angiotensin II receptor blocker (ARB) has been found to induce RAS overactivation. In this study, we investigated the effect of 2 calcium channel blockers (CCBs), cilnidipine (L-/N-type CCB) and amlodipine (L-type CCB), on the RAS activation induced by an ARB in a strain of spontaneously hypertensive rats (SHR/Izm, 10 weeks of age). Methods: Rats intravenously catheterized for blood collection were randomly divided into groups that were administered the vehicle, the ARB valsartan or valsartan combined with one of the 2 CCBs. Their blood and kidneys were collected 270 min after administration. Results: Valsartan increased the plasma angiotensin II (Ang II) level in a dose-dependent manner. Cilnidipine suppressed the increase in plasma renin activity and plasma Ang II levels induced by valsartan, but amlodipine did not. Combined administration of cilnidipine, but not amlodipine, and valsartan significantly reduced the noradrenaline content in the renal cortex. Conclusions: The results of this study suggest that the suppressive effect of cilnidipine on the valsartan-induced increase in RAS activity can be partly explained by its sympatholytic action mediated by N-type calcium channel blockade, and that combined administration of cilnidipine and valsartan might provide a synergistic therapeutic effect.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Aritomi

Niinuma²,

Ogawa³

et al. 2011

Am J Nephrol

View full text Add to dashboard Cite

show abstract

“…In addition, we previously reported that Cil has suppressive effects on the Val-induced increases in RAS activity through its sympatholytic actions that are mediated by N-type calcium channel blockade 34. In the AVOID (Aliskiren in the Evaluation of Proteinuria in Diabetes) trial,49 the combination of a DRI with an ARB was found to have stronger organ-protective effects than ARB monotherapy, suggesting that inhibiting increases in ARB-induced RAS activity promotes the protection of organs and tissues. Taken together, these data suggest that the synergistic organ-protective effects of treatment with Cil and an ARB were attributable to the inhibitory effects of Cil on RAS activation.…”

Section: Discussionmentioning

confidence: 99%

Additive effects of cilnidipine, an L-/N-type calcium channel blocker, and an angiotensin II receptor blocker on reducing cardiorenal damage in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes mellitus

Mori

Aritomi

Niinuma

et al. 2014

DDDT

View full text Add to dashboard Cite

Cilnidipine (Cil), which is an L-/N-type calcium channel blocker (CCB), has been known to provide renal protection by decreasing the activity of the sympathetic nervous system (SNS) and the renin–angiotensin system. In this study, we compared the effects of the combination of Cil and amlodipine (Aml), which is an L-type CCB, with an angiotensin (Ang) II receptor blocker on diabetic cardiorenal damage in spontaneously type 2 diabetic rats. Seventeen-week-old Otsuka Long-Evans Tokushima Fatty rats were randomly assigned to receive Cil, Aml, valsartan (Val), Cil + Val, Aml + Val, or a vehicle (eight rats per group) for 22 weeks. Antihypertensive potencies were nearly equal among the CCB monotherapy groups and the combination therapy groups. The lowering of blood pressure by either treatment did not significantly affect the glycemic variables. However, exacerbations of renal and heart failure were significantly suppressed in rats administered Cil or Val, and additional suppression was observed in those administered Cil + Val. Although Val increased the renin–Ang system, Aml + Val treatment resulted in additional increases in these parameters, while Cil + Val did not show such effects. Furthermore, Cil increased the ratio of Ang-(1–7) to Ang-I, despite the fact that Val and Aml + Val decreased the Ang-(1–7) levels. These actions of Cil + Val might be due to their synergistic inhibitory effect on the activity of the SNS, and on aldosterone secretion through N-type calcium channel antagonism and Ang II receptor type 1 antagonism. Thus, Cil may inhibit the progression of cardiorenal disease in type 2 diabetes patients by acting as an N-type CCB and inhibiting the aldosterone secretion and SNS activation when these drugs were administered in combination with an Ang II receptor blocker.

show abstract

“…The effects of aliskiren combined with another RAAS agent on various surrogate end points in the AVOID, ALOFT, and ALLAY studies (proteinuria, NT–proBNP, LVH) suggest that aliskiren-based combinations may confer incremental vasculoprotective effects that are not accounted for by BP reductions alone and, therefore, may be particularly appealing for treatment of hypertension in patients with diabetes, kidney disease, or the metabolic syndrome 26,41,42,53. More long-term data are needed to confirm its efficacy and safety in these patient populations.…”

Section: Role Of Aliskiren/valsartan In the Hypertension Therapeutic mentioning

confidence: 99%

Aliskiren and valsartan combination therapy for the management of hypertension

Epstein¹

2010

VHRM

View full text Add to dashboard Cite

Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS) are mainstays in hypertension management, especially for patients at high cardiovascular and renal risk. Single blockade of the RAAS with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) confers some cardiorenal protection; however, these agents do not extinguish the RAAS as evidenced by a reactive increase in plasma renin activity (PRA), a cardiovascular risk marker, and incomplete cardiorenal protection. Dual blockade with an ACE inhibitor and an ARB offers no additional benefit in patients with hypertension and normal renal and left ventricular function. Indeed, PRA increases synergistically with dual blockade. Aliskiren, the first direct renin inhibitor (DRI) to become available has provided an opportunity to study the merit of DRI/ARB combination treatment. By blocking the first and rate-limiting step in the RAAS, aliskiren reduces PRA by at least 70% and buffers the compensatory increase in PRA observed with ACE inhibitors and ARBs. The combination of a DRI and an ARB or an ACE inhibitor is an effective approach for lowering blood pressure; available data indicate that such combinations favorably affect proteinuria, left ventricular mass index, and brain natriuretic peptide in patients with albuminuria, left ventricular hypertrophy, and heart failure, respectively. Ongoing outcome studies will clarify the role of aliskiren and aliskiren-based combination RAAS blockade in patients with hypertension and those at high cardiorenal risk.

show abstract

An Issue of Dependence: Implications From the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) Trial

Cited by 8 publications

References 15 publications

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Additive effects of cilnidipine, an L-/N-type calcium channel blocker, and an angiotensin II receptor blocker on reducing cardiorenal damage in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes mellitus

Aliskiren and valsartan combination therapy for the management of hypertension

Contact Info

Product

Resources

About