Addition of aliskiren to olmesartan ameliorates tubular injury in chronic kidney disease patients partly by reducing proteinuria

Nakamura, Tsukasa; Satô, Eiichi; Amaha, Mayuko; Kawagoe, Yasuhiro; Maeda, Sayaka; Yamagishi, Sho‐ichi

doi:10.1177/1470320311422580

Cited by 14 publications

(10 citation statements)

References 29 publications

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“…From these results, it may be inferred that expression of renal hL-FABP in the proximal tubules and urinary excretion of renal hL-FABP changed in response to the amount of ROS produced by activation of ANG II signaling via AT 1a . These results appear to mimic the decrease in urinary hL-FABP that was brought about by inhibition of RAS activation due to the activity of angiotensin-converting enzyme inhibitor or ANG II receptor blocker shown in the clinical studies in patients with CKD and hypertension (18,19,20).…”

Section: Discussionmentioning

confidence: 57%

Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation

Ichikawa

Kamijo‐Ikemori

Sugaya

et al. 2014

American Journal of Physiology-Renal Physiology

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The aim of this study was to assess the renoprotective effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP(+/-)AT1a(+/+)), crossed the L-FABP(+/-)AT1a(+/+) with AT1a knockdown homo mice (L-FABP(-/-)AT1a(-/-)), and generated L-FABP(+/-)AT1a hetero mice (L-FABP(+/-)AT1a(+/-)). After the back-cross of these cubs, L-FABP(+/-)AT1a(-/-) were obtained. To activate the renal RAS, wild-type mice (L-FABP(-/-)AT1a(+/+)), L-FABP(+/-)AT1a(+/+), L-FABP(-/-)AT1a(+/-), L-FABP(+/-)AT1a(+/-), L-FABP(-/-)AT1a(-/-), and L-FABP(+/-)AT1a(-/-) were administered high-dose systemic ANG II infusion plus a high-salt diet for 28 days. In the L-FABP(-/-)AT1a(+/+), RAS activation (L-FABP(-/-)AT1a(+/+)RAS) caused hypertension and tubulointerstitial damage. In the L-FABP(+/-)AT1a(+/+)RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP(-/-)AT1a(+/+)RAS. In the AT1a partial knockout (AT1a(+/-)) or complete knockout (AT1a(-/-)) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP(-/-)AT1a(+/+)RAS or L-FABP(+/-)AT1a(+/+)RAS mice. Renal injury in L-FABP(+/-)AT1a(+/-)RAS mice was significantly attenuated compared with L-FABP(-/-)AT1a(+/-)RAS mice. In both L-FABP(-/-)AT1a(-/-)RAS and L-FABP(+/-)AT1a(-/-)RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.

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Section: Discussionmentioning

confidence: 57%

Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation

Ichikawa

Kamijo‐Ikemori

Sugaya

et al. 2014

American Journal of Physiology-Renal Physiology

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“…Without a control group, Lopez et al and Tang et al demonstrated that add-on aliskiren reduced urinary protein in kidney transplant recipients (n = 12) and immunoglobulin A nephropathy patients (n = 25), respectively [30][31]. A prospective trial conducted by Tsukasa Nakamura et al found that combination therapy with aliskiren and ARBs decreased proteinuria in non-DM CKD patients more effectively than monotherapy alone, however their findings did not reach statistical significance due to the limited number of patients (n = 12 in each group) [32]. By studying 189 non diabetic CKD patients, the present study clearly shows that aliskiren reduced proteinuria in patients with non-DM chronic kidney disease who were receiving ARBs.…”

Section: Discussionmentioning

confidence: 99%

Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease

Chen

et al. 2012

BMC Nephrol

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BackgroundThe renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney disease (CKD). Although dual RAAS inhibition results in worse renal outcomes than monotherapy in high risk type 2 diabetes patients, the effect of dual RAAS inhibition in patients with non-DM CKD is unclear. The aim of this study was to evaluate the potential renoprotective effect of add-on direct renin inhibitor in non-DM CKD patients.MethodsWe retrospectively enrolled 189 non-DM CKD patients who had been taking angiotensin II receptor blockers (ARBs) for more than six months. Patients were divided into an add-on aliskiren group and an ARB monotherapy group. The primary outcomes were a decline in glomerular filtration rate (GFR) and a reduction in urinary protein-to-creatinine ratio at six months.ResultsThe baseline characteristics of the two groups were similar. Aliskiren 150 mg daily reduced the urinary protein-to-creatinine ratio by 26% (95% confidence interval, 15 to 37%; p < 0.001). The decline in GFR was smaller in the add-on aliskiren group (−2.1 vs. -4.0 ml/min, p = 0.038). Add-on aliskiren had a neutral effect on serum potassium in the non-DM CKD patients. In subgroup analysis, the proteinuria-reducing effect of aliskiren was more prominent in patients with a GFR less than 60 ml/min, and in patients with a urinary protein-to-creatinine ratio greater than 1.8. The effect of aliskiren in retarding the decline in GFR was more prominent in patients with hypertensive nephropathy than in those with glomerulonephritis.ConclusionAdd-on direct renin inhibitor aliskiren (150 mg daily) safely reduced proteinuria and attenuated the decline in GFR in the non-DM CKD patients who were receiving ARBs.

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“…The authors suggest that the antiproteinuric effect of aliskiren is independent from its antihypertensive effect [27]. On the other hand, Nakamura et al [28] reported that the combined therapy with aliskiren (300 mg daily) and olmesartan (40 mg daily) for 6 months decreased SBP and SBP, proteinuria, and urinary excretion level of L-fatty acid binding protein (L-FABP), which is a marker of tubular injury, in non-diabetic stage I or II CKD patients more than olmesartan or aliskiren monotherapy. In turn, Lizakowski et al [29] compared the antiproteinuric and hypotensive effects of aliskiren with perindopril in non-diabetic CKD patients.…”

Section: Pharmacology Of Aliskirenmentioning

confidence: 98%

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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Addition of aliskiren to olmesartan ameliorates tubular injury in chronic kidney disease patients partly by reducing proteinuria

Cited by 14 publications

References 29 publications

Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation

Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation

Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease

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

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