Aliskiren, the first direct renin inhibitor: assessing a role in pediatric hypertension and kidney diseases

Abstract

This article provides a review of the role of aliskiren, a direct renin inhibitor, in pediatric hypertension and kidney diseases. Among the many mechanisms involved in regulating BP, the renin-angiotensin-aldosterone system (RAAS) plays a major role. Additionally, the RAAS has been identified as a contributing factor to cardiovascular and renal diseases for more than three decades. The potential benefits of inhibiting the RAAS by aliskiren alone or in combination with other RAAS blockers (ACEIs, ARBs) seem theoretically promising, but one should exercise caution in children, especially in those with significant chronic kidney disease until there is more evidence regarding the safety and efficacy of this new drug in the pediatric population from the ongoing clinical trials.

Renin Angiotensin System Blocker Fetopathy: A Midwest Pediatric Nephrology Consortium Report

“…23 No information concerning its teratogenicity is currently available. Nonetheless, similar to ACEIs and ARBs, aliskiren should not be used during pregnancy.…”

Aliskiren protects against myocardial ischaemia‐reperfusion injury via an endothelial nitric oxide synthase dependent manner

“…It is a new class of antihypertensive agents that act on the renin system via blocking the first and rate‐limiting step in renin‐angiotensin cascade of Ang II activation. DRIs inhibit plasma renin activity (PRA), thereby preventing the conversion of angiotensinogen to angiotensin I; consequently, the levels of both Ang I and Ang II are reduced . It is theoretically a potent agent to block the ARS system to perform its powerful pharmacological effect .…”

Aliskiren: Direct Renin Inhibitor Baru pada Terapi Hipertensi

“…ACEI merupakan inhibitor pembentukan angiotensin II, hal tersebut akan menyebabkan peningkatan aktivitas renin oleh karena rusaknya siklus umpan balik yang normalnya akan menghambat pengeluaran renin dari ginjal. ACEI pun menghambat inaktivasi bradikinin dan substansi P, sehingga memunculkan efek samping batuk dan angioedema (Brown, 2008;Nadeem and Batisky, 2014).…”

“…Bekerja pada RAAS (Nadeem and Batisky, 2014) Sejauh ini hanya inhibitor renin yang dapat menghambat jalur RAAS secara selektif dan efektif dengan memblok renin pada siklus RAAS. ARB mampu memblok reseptor AT-1 secara spesifik, sehingga angiotensin II tidak berinteraksi pada reseptor tersebut.…”

“…Hal tersebut dapat mengakibatkan kerusakan organ target seperti disfungsi renal dan hipertrofi ventrikel kiri. Dengan adanya inhibitor renin yang dapat menekan aktivitas renin, baik dengan monoterapi maupun kombinasi dengan ACEI atau ARB, diharapkan dapat mencegah kerusakan organ target pada hipertensi (Nadeem and Batisky, 2014).…”