Aliskiren reduces albuminuria and oxidative stress, and elevates glomerular filtration rates in Japanese patients with advanced diabetic nephropathy

Ogawa, Susumu; Nako, Kazuhiro; Okamura, Masashi; Senda, Miho; Mori, Takefumi; Ito, Sadayoshi

doi:10.1038/hr.2010.250

Cited by 17 publications

(15 citation statements)

References 10 publications

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“…Our study supports the findings in clinical trials showing the additional effect of aliskiren on RAS-inhibitor treatment in type 2 diabetic hypertensive patients (10, 21). One question that has arisen from these clinical studies is whether the RAS inhibitor dosage, such as 100 mg/day of losartan in the AVOID study, was sufficient for RAS suppression.…”

Section: Discussionsupporting

confidence: 91%

Add-On Aliskiren Elicits Stronger Renoprotection Than High-Dose Valsartan in Type 2 Diabetic KKAy Mice That Do Not Respond to Low-Dose Valsartan

et al. 2012

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We hypothesized that aliskiren provides renoprotection in diabetic animals that did not receive sufficient renoprotection by AT1-receptor antagonist treatment. Type 2 diabetic KKAy mice were treated with group 1: vehicle or group 2: valsartan (15 mg/kg per day) from 12 to 16 weeks of age. The mice were subsequently divided into 4 groups and treated with the following combinations of drugs for another 6 weeks: 1: group 1 kept receiving vehicle, 2: group 2 continuously received 15 mg/kg per day of valsartan (Val-Val15), 3: group 2 received 50 mg/kg per day of valsartan (Val-Val50), 4: group 2 continuously received 15 mg/kg per day of valsartan with 25 mg/kg per day of aliskiren (Val-Val+Ali). Aliskiren exerted significant anti-albuminuric effects, whereas valsartan failed to ameliorate the albuminuria in the first four weeks. Surprisingly, the increasing dosage of valsartan in the Val-Val50 group showed non-significant tendencies to attenuate the albuminuria compared with vehicle infusion. Val-Val+Ali significantly suppressed the development of albuminuria and podocyte injury. Val-Val50 and Val-Val+Ali showed similar suppression of angiotensin II contents in the kidney of KKAy mice. In conclusion, the anti-albuminuric effect that was observed in the type 2 diabetic mice showing no anti-albuminuric effect by valsartan can be attributed to the add-on aliskiren.

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Section: Discussionsupporting

confidence: 91%

Add-On Aliskiren Elicits Stronger Renoprotection Than High-Dose Valsartan in Type 2 Diabetic KKAy Mice That Do Not Respond to Low-Dose Valsartan

et al. 2012

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“…Increased ROSs in CTL deficiency impair peroxisomal/mitochondrial fatty acid oxidation and subsequently increase lipid accumulation, which might induce increased renal injury [42]. Animal and clinical studies have confirmed that antioxidant treatment plays an effective role in T2DM and DN [43].…”

Section: Nagarajrao and Alharbimentioning

confidence: 99%

Relationship Between Oxidant and Antioxidant Enzymes Status in Type 2 Diabetic Patients With Nephropathy in Saudi Population.

Nagarajrao

Alharbi

2018

Asian J Pharm Clin Res

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Objective: Oxidative stress has crucial role in pathogenesis of diabetic complications. Diabetic nephropathy (DN) is an important microvascular complication of diabetes and is widely recognized as the most common cause of the end-stage renal disease (ESRD) seen in clinical practice. Chemically, oxidative stress occurs as a result of increased levels of lipid peroxides and free radical intermediates, as well as a decrease in the total antioxidant capacity. This study analyzed the relationships between oxidant and antioxidant markers of DN in patients with type 2 diabetes mellitus (T2DM).Methods: A descriptive study was taken during the period from November 2016 to August 2017. The present study included 53 patients suffering from T2DM without nephropathy and 51 patients T2DM with nephropathy along with 69 age-and sex-matched healthy controls. Various biochemical parameters, antioxidant enzymes, and malondialdehyde (MDA) levels were measured and compared. Results:The glycosylated hemoglobin (HbA1c), urea, creatinine, microalbuminuria, and MDA levels were significantly increased (p<0.001), and antioxidant enzyme activities such as glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CTL) were significantly decreased (p<0.001) in T2DM with nephropathy patients followed by T2DM without nephropathy and control groups. There were a good negative correlations of HbA1c and GPx (r=−0.79), SOD (r=−0.61) and CTL (r=−0.74) (p≤0.05), whereas there was an excellent positive correlation of MDA concentration (r=0.85, p≤0.05) with HbA1c levels in diabetes with nephropathy. Conclusion:The study illustrated that, in diabetic patients, there is an increased concentration of lipid peroxides which may contribute to decreased levels of cellular antioxidant enzymes, further leading to T2DM with nephropathy. Hence, monitoring of these antioxidant enzymes and microalbuminuria parameters in the early stage of diabetic patients could be vital importance in possible preventing further development of complications. We suggest potential and new multiproperty antioxidants therapy as one of the most important treatment strategies for diabetic patients without nephropathy for the prevention and slowing of diabetic with nephropathy before reaching to ESRD.

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“…Similar to other RAS inhibitors, such as angiotensin converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB), several studies have reported clinical efficacy of aliskiren not only on blood pressure (BP) reduction but also on organ protection [5][6][7][8][9][10]. In addition, ACE-I or ARB have been shown to have a beneficial effect on endothelial function in the patients with hypertension [11,12].…”

Section: Introductionmentioning

confidence: 99%

Acute Effect of Aliskiren on Smoking-Induced Endothelial Dysfunction in Smoker

Uchida¹,

Uchida

Wada³

2014

J Cardiovasc Med Cardiol

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Background: We aimed to examine the acute effect of aliskiren on smoking-induced endothelial dysfunction in smoker.Methods: Nineteen male smokers were enrolled. After all participants smoked a cigarette, their endothelial function was assessed with brachial artery flow mediated dilation (FMD). An hour after the administration of aliskiren, they smoked again, their FMD was assessed again. A month later, all measurements were performed again without the administration of aliskiren as a control. Blood pressure, plasma renin activity, and serum interleukin-6 concentration were also examined at the same time of FMD measurement.Results: A cigarette smoking led to an acute endothelial dysfunction (6.5 ± 1.7% to 3.4 ± 1.0 %, P = 0.02). Aliskiren administration significantly suppressed blood pressure and plasma renin activity, furthermore, improved FMD (6.7 ± 0.5% to 8.1 ± 0.8 %, P = 0.03). Aliskiren significantly reduced serum interleukin-6 concentration, but not in control. Conclusion:Aliskiren has a beneficial effect on smoking-induced acute endothelial dysfunction. MethodsThe study enrolled nineteen male smokers aged 41 ± 2 (27 to 51) years old that had no cardiovascular risk factors other than smoking. All measurements were performed in the early morning, before breakfast, refraining from smoking more than 12 hours. At first, each participant took two puffs of a cigarette which contained 8 mg of tar and 0.7 mg of nicotine. Immediately, endothelial function was assessed with brachial artery flow mediated dilation (FMD) using UNEXEF18G (UNEX Co.Nagoya, Japan) [13]. Then, all participants took a 150 mg of aliskiren. An hour later, following another two puffs of cigarette taken, FMD were evaluated again. Plasma renin activity, serum interleukin-6 (IL-6), thrombomodulin (TM) and asymmetric dimethylarginine (ADMA) concentration were examined before and an hour later. BP was also measured at supine position just before FMD measurement. A month later, all measurements were performed again without the administration of aliskiren as a control. This study was approved by Okayama University Institutional Review Board (accredited ISO9001/2000). All participants gave written consents. Data were presented as means ± SEM. Changes in parameters were evaluated by paired t test. Results with P < 0.05 were deemed statistically significant. ResultsAliskiren administration significantly reduced both systolic and diastolic BP (P < 0.01, each) without any change in pulse rate (Table 1). Plasma renin activity dramatically decreased in all

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Aliskiren reduces albuminuria and oxidative stress, and elevates glomerular filtration rates in Japanese patients with advanced diabetic nephropathy

Cited by 17 publications

References 10 publications

Add-On Aliskiren Elicits Stronger Renoprotection Than High-Dose Valsartan in Type 2 Diabetic KKAy Mice That Do Not Respond to Low-Dose Valsartan

Add-On Aliskiren Elicits Stronger Renoprotection Than High-Dose Valsartan in Type 2 Diabetic KKAy Mice That Do Not Respond to Low-Dose Valsartan

Relationship Between Oxidant and Antioxidant Enzymes Status in Type 2 Diabetic Patients With Nephropathy in Saudi Population.

Acute Effect of Aliskiren on Smoking-Induced Endothelial Dysfunction in Smoker

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