Optimal antiproteinuric dose of aliskiren in type 2 diabetes mellitus: a randomised crossover trial

Persson, Frederik; Reinhard, Henrik; Juhl, Tina R.; Stehouwer, Coen D. A.; Schalkwijk, Casper G.; Danser, A.H. Jan; Boomsma, Frans; Frandsen, Erik; Parving, Hans Henrik

doi:10.1007/s00125-010-1789-6

Cited by 30 publications

(20 citation statements)

References 10 publications

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“…13 Several small studies with aliskiren in diabetes have demonstrated an antiproteinuric effect of monotherapy, enhanced albuminuria reduction with dual RAAS blockade and that the optimal dose for reno-protection is 300 mg once daily. [14][15][16] In a multinational, randomized, double-blind study (AVOID), in 599 patients with hypertension, type 2 diabetes and nephropathy, who are receiving the recommended renoprotective treatment, we showed that the anti-proteinuric effect of aliskiren was independent of its blood pressure-lowering action. 17 The aim of the present trial is to determine the effectiveness and safety of direct renin inhibition with aliskiren compared with placebo in type 2 diabetic patients at high risk of fatal and non-fatal renal and CVD events.…”

Section: Introductionmentioning

confidence: 99%

Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

Parving

Brenner

McMurray

et al. 2012

J Renin Angiotensin Aldosterone Syst

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Introduction: Patients with type 2 diabetes are at enhanced risk for macro- and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel direct renin inhibitor, which lowers plasma renin activity, may thereby provide greater cardio-renal protection compared with angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) alone. Materials and methods: ALTITUDE is a randomized, double-blind, placebo-controlled study in high risk type 2 diabetic patients receiving aliskiren 300 mg once daily or placebo added to recommended cardio-renal protective treatment including ACEi or ARB, but not both. The number of patients randomized was 8606. Results: Baseline characteristics (median, IQR) are: age 65 (58, 72) years, male 68%, BMI 29.1 (25.7, 32.2) kg/m2, cardiovascular disease 47.9%, blood pressure 134.7 (126, 150)/74.3 (67, 81) mmHg, HbA1c 7.5 (6.6, 8.6)%, LDL-cholesterol 2.4 (1.9, 3.0) mmol/L, haemoglobin 130 (119, 143) g/L, serum creatinine 115 (91, 137) µmol/L, eGFR 51.7 (42, 65) ml/min per 1.73 m2, geometric mean UACR 198.9 (52, 2886) mg/g and frequency of micro/macroalbuminuria 25.7% and 58.2%. ALTITUDE is an event-driven trial to continue until 1628 patients experience a primary cardiovascular-renal event. Conclusions: ALTITUDE will determine the potential cardio-renal benefit and safety of aliskiren in combination with ACEi or ARB in high risk patients with type 2 diabetes.

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Section: Introductionmentioning

confidence: 99%

Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

Parving

Brenner

McMurray

et al. 2012

J Renin Angiotensin Aldosterone Syst

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“…Changes in exposure did not correlate with the severity of renal insufficiency, as assessed by CL CR [19]. The accumulation of aliskiren at steady state (indicated by the AUC from 0 and 24 hours [AUC 24 ] on day 7 vs day 1) was similar in healthy subjects (1.79) and each subgroup of subjects with renal impairment (1.39-1.99). The authors conclude that exposure to aliskiren is increased by renal impairment, but does not correlate with the severity of renal insufficiency (CL CR ); therefore, adjustment of the starting dose of aliskiren is not required in patients with renal impairment [19].…”

Section: Pharmacology Of Aliskirenmentioning

confidence: 88%

“…Additionally, 65% patients achieved blood pressure response (mean DBP < 90 or a 10 mmHg decrease, or mean SBP < 140 or a 20 mmHg decrease), and 30% achieved blood pressure control (mean SBP < 140 mmHg and mean DBP < 90mmHg) at the week 8 endpoint [23]. Persson et al [24] examined the antiproteinuric effect of increasing doses of aliskiren (up to 600 mg) in hypertensive patients with diabetic nephropathy (eGFR: 85 mL/min/1.73 m 2 ). Treatment with aliskiren 150, 300 and 600 mg daily reduced urinary albumin excretion rate by 36, 48 and 52%, and 24 h SBP by 4.5, 8.0 and 9.2 mmHg, respectively, compared with placebo.…”

Section: Pharmacology Of Aliskirenmentioning

confidence: 99%

“…Treatment with aliskiren 150, 300 and 600 mg daily reduced urinary albumin excretion rate by 36, 48 and 52%, and 24 h SBP by 4.5, 8.0 and 9.2 mmHg, respectively, compared with placebo. The authors found that there was no improved antiproteinuric effect of aliskiren at the dose 600 mg daily, compared with the maximal recommended antihypertensive dose of 300 mg [24]. In 2011, Morishita et al [25] published a paper on effects of aliskiren on BP and the predictive biomarkers for CVD in hemodialysis (HD)-dependent CKD patients with hypertension.…”

Section: Pharmacology Of Aliskirenmentioning

confidence: 99%

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Aliskiren – an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease

Łukawski¹,

Baranowicz-Gąszczyk²

2017

J Pre Clin Clin Res.

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Łukawski K, Baranowicz-Gąszczyk I. Aliskiren -an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease. J Pre-Clin Clin Res. 2017; 11(1): 81-85. doi: 10.26444/jpccr/75295 Abstract Introduction. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of hypertension, cardiovascular diseases (CVDs) and chronic kidney disease (CKD). Drugs affecting the RAAS system, such as angiotensinconverting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), are commonly used in the treatment of hypertension and heart failure. These drugs are also effective in reducing proteinuria and may, at least, delay end-stage renal disease in both diabetic and non-diabetic proteinuric CKD. However, novel drugs are needed to more effectively suppress the RAAS system and the progression of CKD. Aliskiren is the first direct renin inhibitor which has been approved for the treatment of hypertension. Additionally, a number of clinical studies have shown the antiproteinuric effect of aliskiren.Objective. This review focuses on the antihypertensive and antiproteinuric effects of aliskiren in patients with CKD. The pharmacology of aliskiren in these patients is also provided. Conclusions. Aliskiren-based hard endpoint large trials in non-diabetic nephropathy are needed in order to clarify the use of aliskiren in CKD patients.

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“…Aliskiren 150, 300 and 600 mg reduced UAER significantly by 36%, 48% and 52% respectively compared with placebo 26 Persson et al [93] 2010…”

Section: Safety Studiesmentioning

confidence: 99%

Aliskiren as a novel therapeutic agent for hypertension and cardio-renal diseases

Rashikh

Ahmad

Pillai

et al. 2011

Journal of Pharmacy and Pharmacology

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Objectives High blood pressure (BP) is a major risk factor for cardiovascular and renal complications. A majority of treated hypertensive patients still complain of high BP. The renin-angiotensin aldosterone system (RAAS) has been a centre-stage target for all the cardiovascular and cardio-renal complications. Aliskiren, is the first direct renin inhibitor (DRI) to be approved by the US FDA. Renin controls the ratelimiting step in the RAAS cascade and hence is the most favorable target for RAAS suppression. Key findings This review article strives to summarize the pharmacokinetic, preclinical and clinical studies done so far pertaining to the efficacy of aliskiren. Further, the pharmacology of aliskiren has been comprehensively dealt with to enhance understanding so as to further research in this unfathomed area in the multitude of cardiovascular disorders and renal diseases. Summary Aliskiren has been shown to have comparable BP-lowering effects to other RAAS inhibitors. Recent clinical trials have indicated that it might contribute significantly in combination with other agents for the protection of end-organ diseases.

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Optimal antiproteinuric dose of aliskiren in type 2 diabetes mellitus: a randomised crossover trial

Cited by 30 publications

References 10 publications

Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

Aliskiren – an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease

Aliskiren as a novel therapeutic agent for hypertension and cardio-renal diseases

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