Renin-angiotensin-aldosterone system blockade for nephroprotection: current evidence and future directions

Tylicki, Leszek; Lizakowski, Sławomir; Rutkowski, Bolesław

doi:10.5301/jn.5000134

Cited by 47 publications

(32 citation statements)

References 87 publications

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“…The renoprotective effects of the RAAS-inhibiting drugs have been shown to involve the normalization of glomerular hyperperfusion and hyperfiltration, restoration of glomerular barrier function, and a reduction of the non-hemodynamic effects of angiotensin II and aldosterone [21]. …”

Section: Discussionmentioning

confidence: 99%

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

Eren

Günal

Bakır

et al. 2014

Kidney Blood Press Res

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Background/Aims: The aim of the present study was to investigate the effect of combination of aliskiren with paricalcitol on experimental diabetic nephropathy (DN) model in rats. Methods: Forty male Sprague Dawley rats were divided into 5 groups of 8 rats each, namely the control (Group C), diabetes (Group D), aliskiren (Group A), paricalcitol (Group P), and aliskiren plus paricalcitol (Group A+P) groups. Aliskiren was given by oral-gavage at a dose of 50 mg/kg/day once daily for 12 weeks. Paricalcitol was given by intraperitoneally at a dose of 0,4 µg/kg/three day of week for 12 weeks. Renal function parameters, oxidative stress biomarkers, mRNA expression of renin-angiotensin system parameters and kidney histology were determined. Results: Group A+P had lower mean albümin-to-creatinine ratio (ACR) (p=0.004) as well as higher creatinine clearance (CCr) (p<0.005) than the diabetic rats (Group D). Combination therapy significantly increased CCr (Group A+P vs Group A, p<0.005; Group A+P vs Group P, p=0.022) and reduced ACR (Group A+P vs Group A, p=0.018; Group A+P vs Group P, p<0.005) when compared to monotherapy. Serum malondialdehyde levels were significantly lower (p=0.004); glutathion levels (p=0.003), glutathion peroxidase (p=0.004) and superoxide dismutase (p<0.005) activities were significantly higher in group A+P than in group D. The mean scores of mRNA expression of renin (p<0.005), angiotensin II (p=0.012) and angiotensin type 1 receptor (p=0.018) in group A+P were significantly lower. Although combination therapy showed no additional effect on oxidative system, renin-angiotensin system and renal histology, aliskiren plus paricalcitol significantly decreased interstitial fibrosis volume when compared to monotherapy (Group A+P vs Group A, p<0.005; Group A+P vs Group P, p=0.002). Conclusion: Our data seem to suggest a potential role of aliskiren plus paricalcitol acting synergystically for reducing the progression of diabetic nephropathy in an experimental rat model.

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Section: Discussionmentioning

confidence: 99%

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

Eren

Günal

Bakır

et al. 2014

Kidney Blood Press Res

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“…We considered her condition as a minor flare. In addition, she started to drink GFJ because her blood TAC concentration was below the target range, although there was the other treatment option of adding angiotensin II receptor blockers (ARBs), which may decrease proteinuria and delay the progression of chronic nephropathies (10). GFJ increased the TAC blood trough (C12) level from 4.1 to 12.8 ng/mL (3.1-fold) and was effective in decreasing proteinuria, which may be the effect of TAC to stabilize the podocyte cytoskeleton through the inhibition of calcineurin expression (11).…”

Section: Resultsmentioning

confidence: 99%

Efficacy and Safety of Grapefruit Juice Intake Accompanying Tacrolimus Treatment in Connective Tissue Disease Patients

et al. 2016

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Objective It is well known that grapefruit juice (GFJ) elevates the blood tacrolimus (TAC) concentration. We investigated the efficacy and safety of GFJ intake with TAC in cases of connective tissue diseases in which the TAC blood concentration was insufficiently high for clinical improvement, even when 3 mg/day or more of TAC was administered. Methods Seven patients took 200 mL of GFJ every day. The trough levels of the TAC blood concentration were measured before and after GFJ intake and the clinical courses were monitored thereafter. Results First, we surveyed the blood TAC trough levels of 30 recent patients who took 3 mg/day of TAC, and found that 21 patients (70%) did not achieve the minimum target TAC concentration (>5 ng/mL). Seven patients took GFJ due to a lack of efficacy and a relatively low TAC blood concentration. GFJ increased the TAC level from 4.3±2.4 ng/mL to 13.8±6.9 ng/mL (average increase: 3.3-fold). GFJ was also effective in achieving a clinical improvement in most cases without causing any severe adverse events, and it helped to decrease the dosages of glucocorticoid and TAC. In some cases, the blood TAC concentration fluctuated for no apparent reason. Conclusion GFJ intake was effective for the elevation of TAC concentration by approximately three fold and clinical improvement, but special care is required for monitoring its influence on concomitantly used drugs as well as TAC concentration. The addition of GFJ to TAC treatment could be an efficacious treatment option, when the plasma TAC concentration does not reach the minimal target concentration.

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“…Several large randomized, controlled trials evidenced the renoprotective potential of the ACEIs and ARBs in nephropathies of almost any etiology [10]. In non-diabetic renal diseases, ACEIs are currently the best documented treatment to delay the progression of nephropathy.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is necessary to search for therapeutic strategy which can enhance RAAS blockade and further improve renal outcome. Of particular need is to find the optimal combination of different RAAS blocking drugs and establish the optimal dosing of these agents [10]. To gain insight into this issue, we performed the study to compare the influence of (i) the combination therapy with ARB, telmisartan plus renin inhibitor, aliskiren, (ii) the combination therapy with ARB, telmisartan plus mineralocorticoid receptor antagonist, eplerenone and (iii) monotherapy with ARB, telmisartan in doses twofold higher than usually used on albuminuria regarded as an independent risk factor for renal disease progression and a surrogate marker of kidney injury extent.…”

Section: Introductionmentioning

confidence: 99%

The Enhanced Renin-Angiotensin-Aldosteron System Pharmacological Blockade - Which is the Best?

Tylicki

Lizakowski

Rutkowski

et al. 2012

Kidney Blood Press Res

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Background/Aims: Pharmacological inhibition of renin-angiotensin-aldosteron system (RAAS) may reduce proteinuria and the rate of chronic kidney disease progression. The aim was to compare the effects on albuminuria of the therapy with either: i) telmisartan 80 mg and aliskiren 300 mg, ii) telmisartan 80 mg and eplerenone 50 mg, iii) telmisartan 160 mg as monotherapy. Design and patients: Randomized, double-center, double-blind, cross-over, three treatments-three periods of 8 weeks each study. 18 patients with non-diabetic proteinuric CKD stage 1-3 completed the protocol. Results: There was significant difference in albuminuria between studied therapies (ANOVA; p<0.01). The combination therapy with telmisartan plus aliskiren decreased albuminuria more effectively than the treatment with telmisartan plus eplerenone and monotherapy with telmisartan 160 mg OD [376 mg/g creatinine (286-686) vs. 707 (502-1204) vs. 525 (318-763); post-hoc p<0.01 and p<0.05, respectively]. Conclusions: The study demonstrated that the combination therapy with angiotensin receptor blocker (ARB) and renin inhibitor was more effective in albuminuria lowering than the concomitant usage of ARB and mineralocorticoid receptor antagonist as well as than ARB in doses two-fold higher than usually used in treatment of hypertension in patients with non-diabetic CKD and that this higher antiproteinuric efficacy was independent on changes in blood pressure.

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Renin-angiotensin-aldosterone system blockade for nephroprotection: current evidence and future directions

Cited by 47 publications

References 87 publications

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

Efficacy and Safety of Grapefruit Juice Intake Accompanying Tacrolimus Treatment in Connective Tissue Disease Patients

The Enhanced Renin-Angiotensin-Aldosteron System Pharmacological Blockade - Which is the Best?

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