Role of aliskiren in blood pressure control and renoprotection

Trimarchi, Hernán

doi:10.2147/ijnrd.s6653

Cited by 14 publications

(13 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Aliskiren is poorly absorbed, with an absolute oral bioavailability of 2.5%, and maximum plasma aliskiren concentrations are reached within 1–3 hours of oral administration [26]. Steady-state plasma concentrations are reached 5–8 days after the initiation once-daily oral administration of aliskiren.…”

Section: Aliskiren – the First Direct Renin Inhibitormentioning

confidence: 99%

“…One concern may be that high levels of renin and prorenin can activate the PPR receptor, which can possibly initiate ERK1/2 signaling, TGF-β activation, and other potentially serious complications [8,26]. Fortunately, some studies have shown that despite a significant increase in renin concentration, the concentrations of prorenin and TGF-β remain unchanged and aliskiren can reduce in vivo gene expression of the PPR receptor [30,34,35].…”

Section: Aliskiren – the First Direct Renin Inhibitormentioning

confidence: 99%

See 1 more Smart Citation

Direct renin inhibition – a promising strategy for renal protection?

2013

View full text Add to dashboard Cite

Activation of the renin–angiotensin–aldosterone system (RAAS) plays a key role in the progression of chronic kidney disease (CKD). RAAS inhibitors, such as angiotensin converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs), decrease the rate of progression of diabetic and non-diabetic nephropathies and are first-line therapies for CKD. Although these agents are highly effective, current therapeutic strategies are unable to sufficiently suppress the RAAS and stop CKD progression. Aliskiren, the first in a new class of RAAS-inhibiting agents (direct renin inhibitors) has been approved to treat hypertension. Aliskiren exerts renoprotective, cardioprotective, and anti-atherosclerotic effects in animal models that appear to be independent of its blood pressure lowering activity. Early clinical studies using urinary protein excretion as a marker of renal involvement suggest a possibly novel role for aliskiren in treating CKD. This review discusses the antiproteinuric efficacy and safety of aliskiren and considers the evidence for its potential renoprotection.

show abstract

Section: Aliskiren – the First Direct Renin Inhibitormentioning

confidence: 99%

Section: Aliskiren – the First Direct Renin Inhibitormentioning

confidence: 99%

Direct renin inhibition – a promising strategy for renal protection?

2013

View full text Add to dashboard Cite

show abstract

“…The drug occupies a specific site within the enzymatic pocket of the renin/prorenin receptor, thereby blocking the function of this enzyme [17]. Because the RAAS cascade begins with renin and because aliskiren may exert renoprotective effects [18,19,20], we aimed to examine the effects of aliskiren for prevention of CIN using a rat model. In addition – as aliskiren may reduce vascular endothelial growth factor (VEGF) expression [21], which is increased in acute kidney injury [22] – we assessed whether tubular VEGF expression can be diminished by the administration of aliskiren immediately before the experimental induction of CIN.…”

Section: Introductionmentioning

confidence: 99%

“…The potential usefulness of direct renin inhibition for preventing CIN has not been previously examined neither in animal models nor in humans. This strategy is particularly interesting as a complete blockade with the use of ACE-I and angiotensin receptor blockers with or without aldosterone receptor blockers is not easy to achieve, and side effects are not uncommon [18]. …”

Section: Introductionmentioning

confidence: 99%

Effect of the Direct Renin Inhibitor Aliskiren in the Prevention of Experimental Contrast-Induced Nephropathy in the Rat

Kedrah

Arı²,

Alahdab³

et al. 2012

Kidney Blood Press Res

View full text Add to dashboard Cite

Background: Renal vasoconstriction, activated by the renin-angiotensin system, plays a pivotal role in the pathogenesis of contrast-induced nephropathy (CIN). The purpose of this study was to evaluate the effect of aliskiren, a direct renin inhibitor, for the prophylaxis of experimental CIN in the rat. Methods: Thirty-two Wistar albino rats were divided into four groups of 8 rats each, namely the control (C), aliskiren (A), contrast media (CM) and aliskiren plus contrast media (ACM) groups. Aliskiren was given orally at a dose of 50 mg/kg/day once daily for 5 consecutive days. CIN was induced by intravenous administration of indomethacin, N-nitro-L-arginine methyl ester and high-osmolar contrast medium meglumine amidotrizoate. Renal function parameters, kidney histology and tubular expression of vascular endothelial growth factor were determined. Results: Mean serum creatinine was significantly lower (p < 0.001) and mean creatinine clearance was higher (p < 0.001) in the ACM group compared with the CM group. However, there were no differences between the ACM and CM groups in terms of tubular necrosis, proteinaceous casts, medullary congestion and vascular endothelial growth factor expression. Conclusion: Our preliminary data seem to suggest a potential role of aliskiren for the prophylaxis of CIN in an experimental rat model.

show abstract

“…Блокируя активность ренина, Алискирен тем самым предотвращает образование ос-новных маркеров сосудистого риска -ангиотензина I и II типа (АТ I и AT II) и реализацию органоповреждающего действия. В ряде клинических исследований Алискирен зарекомендовал себя как эффективный антигипертензив-ный препарат [5,6,7]. В последние годы, в соответствии с международными и отечественными рекомендациями по лечению АГ, частота применения комбинированной антигипертензивной терапии у пациентов с СД2 не-уклонно возрастает, в том числе с использованием так на-зываемой «двойной ангиотензиновой блокады» [3].…”

unclassified

The efficacy and safety of dual blockage of the renin-angiotensin-aldosterone system in patients with type 2 diabetes, hypertension and obesity without renal dysfunction

A¹,

Викулова²,

E³

et al. 2012

Obes. metabol.

View full text Add to dashboard Cite

The purpose of the study was to evaluate the clinical efficacy and safety of dual RAAS blockage during treatment with angiotensin-converting enzyme (ACE) inhibitors in combination with a direct renin inhibitor (PIR) aliskiren versus combination therapy with ACE inhibitors and angiotensin receptor blocker II (ARB) valsartan in patients with type 2 diabetes mellitus (T2DM), arterial hypertension (AH) and obesity, without renal dysfunction. Materials and methods. The study included 26 patients with T2DM (10 men and 16 women, mean age 59,0±6,2 years) with inadequate control of blood pressure (over 130 and/or 80 mm Hg) on prior antihypertensive therapy and without renal dysfunctions (glomerular filtration rate (GFR) 60 ml/min/1, 73 m2 and the of albumin/creatinine (A/C) ratio in the morning urine sample 10 mg/mol). After screening with the continuation of the initial therapy, including ACE inhibitors, 14 patients were added aliskiren 150–300 mg/day, 12 patients – valsartan 80–160 mg/day. Evaluation of the treatment effectiveness in terms of blood pressure (mean of three consecutive measurements in the sitting position) and the parameters of renal function (serum creatinine and potassium, GFR, A/C ratio in the urine) was performed at 4, 12 and 24 weeks of therapy. Results. In the group of patients treated with aliskiren, after 4 weeks of treatment a significant decrease in systolic and diastolic blood pressure (SBP and DBP, respectively) was noted as compared to baseline: 146,1 and 138,9 mm Hg, p0,05, 87,1 and 81,1 mm Hg, p 0,05, respectively; with systolic BP after 24 weeks of treatment decreased to 127,8 (-18,2 mm Hg), p0,05, diastolic BP to 75,0 (-12, 1 mm Hg), p0,05, the target blood pressure (≤130/80 mm Hg) was achieved in 83% of patients. The group of patients treated with valsartan, after 4 weeks of therapy showed a significant reduction in systolic BP 148 and 141,6 mm Hg, p 0,05, diastolic BP - to 85,8 and 81,7 mm Hg, p=0,059; after 24 weeks systolic BP decreased to 128,7 (-19,3 mm Hg), p=0,05, diastolic BP – to 77,5 (-8,3 mm Hg), p=0,07, the target blood pressure was achieved in 78% of patients. When monitoring the safety of therapy in terms of potassium, serum creatinine, GFR, and A/C urine ratio statistically significant differences between the groups at 4, 12, 24 weeks of treatment were observed. Conclusion. Results of the study demonstrate the efficacy and safety of dual RAAS blockage in patients with T2DM and obesity with no prior renal impairment.

show abstract

Role of aliskiren in blood pressure control and renoprotection

Cited by 14 publications

References 80 publications

Direct renin inhibition – a promising strategy for renal protection?

Direct renin inhibition – a promising strategy for renal protection?

Effect of the Direct Renin Inhibitor Aliskiren in the Prevention of Experimental Contrast-Induced Nephropathy in the Rat

The efficacy and safety of dual blockage of the renin-angiotensin-aldosterone system in patients with type 2 diabetes, hypertension and obesity without renal dysfunction

Contact Info

Product

Resources

About