Renal Effects of Aliskiren Compared With and in Combination With Irbesartan in Patients With Type 2 Diabetes, Hypertension, and Albuminuria

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

doi:10.2337/dc09-0168

Cited by 148 publications

(116 citation statements)

References 23 publications

(29 reference statements)

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“…Levels of biomarkers of cardiovascular risk measured in our study were mostly unchanged during aliskiren treatment. This is in agreement with previous short-term studies [5,7]. Of note, aldosterone levels tended to decrease with all doses, which warrants further investigation, since this is a small study and the connection between RAAS blockade (i.e.…”

Section: Discussionsupporting

confidence: 80%

“…Several dosage studies [3,4] have demonstrated dosedependent antiproteinuric effects. After the introduction of the renin inhibitor aliskiren and evidence of its antiproteinuric effects [2,5] we aimed to investigate the antiproteinuric effect of increasing doses of aliskiren, by comparing urinary albumin excretion rate (UAER) during placebo and after 2 months of treatment with aliskiren 150 mg, 300 mg or 600 mg once daily. In addition we measured biochemical data of the RAAS and biomarkers of cardiovascular risk.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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Aim The optimal antiproteinuric dose of aliskiren is unknown. This study compared the effect of placebo and increasing doses of aliskiren on urinary albumin excretion rate (UAER). Methods The trial was a double-blind crossover design. Twenty-six patients with type 2 diabetes mellitus, hypertension and albuminuria were randomised to 2-month treatments with placebo or aliskiren 150 mg, 300 mg or 600 mg once daily, in random order. Primary endpoint was change in UAER; secondary endpoints included changes in 24-h BP, GFR, biomarkers and components of the reninangiotensin-aldosterone system. Results Placebo geometric mean UAER was 350 mg/day, mean 24-h BP was 137/81 (SD 12/9) mmHg, GFR was 85 (SD 26) ml min −1 1.73 m −2 . Aliskiren 150, 300 and 600 mg daily reduced UAER significantly by 36% (95% CI 17-51), 48% (33-60) and 52% (38-63) respectively (p<0.001) compared with placebo.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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“…All strategies reduce proteinuria compared with single-agent therapy (5)(6)(7)(8)(9)(10)(11), but hyperkalemia is a risk (12,13). Regimens including an ACE inhibitor and ARB or either drug and DRI are not recommended not only because of the risk of hyperkalemia but also because of renal failure and hypotension, which were seen in large clinical trials (14,15).…”

Section: Introductionmentioning

confidence: 99%

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Buren

Adams‐Huet

Nguyen³

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the cornerstones of pharmacologic therapy in diabetic nephropathy. Mineralocorticoid receptor blockers reduce proteinuria as single agents or add-on therapy to other renin-angiotensin-aldosterone system-inhibiting drugs in these patients. The long-term benefits and ultimate role of mineralocorticoid receptor blockers in diabetic nephropathy remain unknown. A clinical trial previously showed that the kalemic effect of spironolactone is higher than losartan when added to lisinopril in patients with diabetic nephropathy. The purpose of this study was to investigate if renal potassium handling was primarily responsible for that observation.Design, setting, participants, & measurements In a blinded, randomized, three-arm placebo-controlled clinical trial, 80 participants with diabetic nephropathy taking lisinopril (80 mg) were randomized to spironolactone (25 mg daily), losartan (100 mg daily), or placebo (trial dates from July of 2003 to December of 2006). Serum potassium, aldosterone, and 24-hour urine sodium, potassium, and creatinine were measured over 48 weeks. Differences were analyzed with repeated measures mixed models.Results Mean follow-up serum potassium was 5.0 mEq/L for spironolactone, 4.7 mEq/L for losartan (P=0.05 versus spironolactone), and 4.5 mEq/L for placebo (P,0.001 versus spironolactone; P=0.03 versus losartan). The difference in serum potassium was 0.23 mEq/L for losartan versus placebo (P=0.02), 0.43 mEq/L for spironolactone versus placebo (P,0.001), and 0.2 mEq/L for spironolactone versus losartan (P=0.05). Serum and urine potassium excretion and secretion rates were similar between groups throughout the study.Conclusion Spironolactone raised serum potassium more than losartan in patients with diabetic nephropathy receiving lisinopril, despite similar renal sodium and potassium excretion. This finding suggests that extrarenal potassium homeostasis contributes to hyperkalemia in these patients. A better understanding of extrarenal potassium homeostasis will provide an opportunity to use this drug more safely in patients with diabetic nephropathy as well as other patient populations.

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“…In fact, several animal studies and clinical trials showed the efficacy of this combination on cardiovascular outcomes. 19,[35][36][37][38] The effects of the combination of DRIs and ACEIs or ARBs on post-MI outcomes were investigated in the ASPIRE (Aliskiren Study in Post-MI patients to Reduce rEmodelling) study. 39 In this study, the addition of aliskiren to a standard optimal medical regimen, including an ACEI or an ARB, did not result in benefit with respect to ventricular remodeling compared to placebo and was associated with more adverse events in high-risk post-MI patients with LV Figure 4 Oxidative stress and pro-inflammatory cytokine expression in the heart at 28 days after myocardial infarction (MI).…”

Section: Discussionmentioning

confidence: 99%

Aliskiren in combination with valsartan exerts synergistic protective effects against ventricular remodeling after myocardial infarction in mice

et al. 2011

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The efficacy of aliskiren, a direct renin inhibitor, in ventricular remodeling after myocardial infarction (MI) compared with conventional renin-angiotensin system (RAS) inhibitors remains to be defined. This study was performed to examine the protective effects of aliskiren and its addition to valsartan, an angiotensin-II receptor blocker, against ventricular remodeling after MI. MI was induced in 8-to 12-week-old C57BL/6 mice by ligating the left anterior descending artery. At 3 days after MI, mice were divided into five groups and were treated with the following: (1) phosphate-buffered saline (PBS); (2) hydralazine (10 mg kg -1 day -1 ); (3) valsartan (8 mg kg -1 day -1 ); (4) aliskiren (25 mg kg -1 day -1 ); and (5) combined aliskiren (25 mg kg -1 day -1 ) and valsartan (8 mg kg -1 day -1 ). With these doses of drugs, blood pressure-lowering effects compared with the PBS group were similar among the treated groups in sham-operated mice. At 28 days after MI, echocardiographic, hemodynamic and histological assessments demonstrated that monotherapy with valsartan or aliskiren alone significantly and similarly ameliorated ventricular remodeling after MI compared with the PBS and the hydralazine groups. Combination therapy of valsartan and aliskiren more greatly improved ventricular remodeling after MI with enhancement of angiogenesis and greater attenuation of tissue oxidative stress and inflammation. Our results indicate that aliskiren can be an alternative to conventional RAS inhibitors in the treatment of post-MI patients. Moreover, the dual therapy of valsartan and aliskiren may be more beneficial than either monotherapy. Further clinical trials will be warranted to sufficiently assess the safety and the efficacy of the use of aliskiren in post-MI patients.

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Renal Effects of Aliskiren Compared With and in Combination With Irbesartan in Patients With Type 2 Diabetes, Hypertension, and Albuminuria

Cited by 148 publications

References 23 publications

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

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

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Aliskiren in combination with valsartan exerts synergistic protective effects against ventricular remodeling after myocardial infarction in mice

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