The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

Harel, Ziv; Gilbert, Cameron; Wald, Ron; Bell, Chaim M.; Perl, Jeff; Juurlink, David N.; Beyene, Joseph; Shah, Prakesh S.

doi:10.1136/bmj.e42

Cited by 111 publications

(60 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it is unclear whether ALK may effectively induce regression of cardiac hypertrophy. Although the combination of ALK with an ACEI or an ARB can synergistically attenuate both 1006 www.nature.com/aps Weng LQ et al Acta Pharmacologica Sinica npg hypertrophy and dysfunction in hypertensive patients [8,9] , a systematic review of randomized, controlled clinical trials has shown that combined therapy is associated with a higher risk of hyperkalemia than monotherapy with an ACEI, an ARB or ALK [10] . In addition, some patients are intolerant of ACEI or ARB, whereas ALK is well tolerated [11] .…”

Section: Introductionmentioning

confidence: 99%

Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice

Weng

Zhang

et al. 2014

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Aliskiren (ALK) is a renin inhibitor that has been used in the treatment of hypertension. The aim of this study was to determine whether ALK could ameliorate pressure overload-induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action. Methods: Transverse aortic constriction (TAC) was performed in mice to induce heart pressure overload. ALK (150 mg·kg -1 ·d -1, po), the autophagy inhibitor 3-methyladenine (10 mg·kg -1 per week, ip) or the PKCβI inhibitor LY333531 (1 mg·kg, po) was administered to the mice for 4 weeks. Heart hypertrophy, fibrosis and function were evaluated based on echocardiography, histological and biochemical measurements. Mechanically stretched-cardiomyocytes of rats were used for in vitro experiments. The levels of signaling proteins were measured using Western blotting, while the expression of the relevant genes was analyzed using real-time QRT-PCR. Results: TAC induced marked heart hypertrophy and fibrosis, accompanied by high levels of Ang II in plasma and heart, and by PKCβI/α and ERK1/2 phosphorylation in heart. Meanwhile, TAC induced autophagic responses in heart, i.e. increases in autophagic structures, expression of Atg5 and Atg16 L1 mRNAs and LC3-II and Beclin-1 proteins. These pathological alterations in TAC-mice were significantly ameliorated or blocked by ALK administration. In TAC-mice, 3-methyladenine administration also ameliorated heart hypertrophy, fibrosis and dysfunction, while LY333531 administration inhibited ERK phosphorylation and autophagy in heart. In mechanically stretched-cardiomyocytes, CGP53353 (a PKCβI inhibitor) prevented ERK phosphorylation and autophagic responses, while U0126 (an ERK inhibitor) blocked autophagic responses. Conclusion: ALK ameliorates heart hypertrophy, fibrosis and dysfunction in the mouse model in setting of chronic pressure overload, via suppressing Ang II-PKCβI-ERK1/2-regulated autophagy.

show abstract

Section: Introductionmentioning

confidence: 99%

Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice

Weng

Zhang

et al. 2014

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…16 The efficacy of RAAS blockade intensification in an attempt to further reduce residual proteinuria is, however, limited by side effects, such as hyperkalemia and hypotension. 17,18 Adjunctive therapies, which can offer the lowering of residual proteinuria but without these drawbacks, may improve renal and cardiovascular protection.…”

mentioning

confidence: 99%

Active Vitamin D Treatment for Reduction of Residual Proteinuria

Borst

Hajhosseiny

Tamez

et al. 2013

Journal of the American Society of Nephrology

131

View full text Add to dashboard Cite

Despite renin-angiotensin-aldosterone system blockade, which retards progression of CKD by reducing proteinuria, many patients with CKD have residual proteinuria, an independent risk factor for disease progression. We aimed to address whether active vitamin D analogs reduce residual proteinuria. We systematically searched for trials published between 1950 and September of 2012 in the Medline, Embase, and Cochrane Library databases. All randomized controlled trials of vitamin D analogs in patients with CKD that reported an effect on proteinuria with sample size$50 were selected. Mean differences of proteinuria change over time and odds ratios for reaching $15% proteinuria decrease from baseline to last measurement were synthesized under a random effects model. From 907 citations retrieved, six studies (four studies with paricalcitol and two studies with calcitriol) providing data for 688 patients were included in the meta-analysis. Most patients (84%) used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker throughout the study. Active vitamin D analogs reduced proteinuria (weighted mean difference from baseline to last measurement was 216% [95% CI, 213% to 218%]) compared with controls (16% [95% CI, 0% to 112%]; P,0.001). Proteinuria reduction was achieved more commonly in patients treated with an active vitamin D analog (204/390 patients) than control patients (86/298 patients; OR, 2.72 [95% CI, 1.82 to 4.07]; P,0.001). Thus, active vitamin D analogs may further reduce proteinuria in CKD patients in addition to current regimens. Future studies should address whether vitamin D therapy also retards progressive renal functional decline. 24: 186324: -187124: , 201324: . doi: 10.1681 CKD is a worldwide health burden, affecting about 15% of the Western adult population. 1 CKD is associated with premature death, cardiovascular disease, infection, and cancer, and it consumes disproportionate health care resources. [2][3][4] The mainstay of current CKD treatment is pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Although these drugs may retard progression of both renal and cardiovascular disease 5-9 partly through their capacity to reduce proteinuria, 10,11 progression to ESRD and cardiovascular complications cannot be prevented in many CKD patients. J Am Soc NephrolA recent single-level meta-analysis including over 2 million participants showed that albuminuria is independently associated with mortality and ESRD, regardless of age. 12 The amount of residual albuminuria/proteinuria under RAAS blockade is a strong predictor of both long-term renal disease progression 13,14 and cardiovascular complications, 15

show abstract

“…This is important, bearing in mind that trial definitions may not reflect the clinical significance of a side effect. For instance, combination therapy is associated with an increased risk of moderate hyperkalemia (serum potassium >5.5 mEq/l) but not of clinically significant hyperkalemia (serum potassium >6 mEq/l) compared with monotherapy [Harel et al 2012]. Be that as it may, these studies clearly show that combined RAS inhibitors should be avoided in patients with basal normal or nearly normal blood pressure and in those with basal serum potassium concentration greater than 5 mEq/l.…”

Section: Dual Ras Blockadementioning

confidence: 95%

Direct renin inhibition: extricating facts from façades

Juncos¹

2013

Therapeutic Advances in Cardiovascular Disease

View full text Add to dashboard Cite

Abstract:The renin-angiotensin system (RAS) affects vascular tone, cardiac output and kidney function. By these means the RAS plays a key role in the pathogenesis of arterial hypertension. As a result, RAS inhibition is highly effective not only in lowering blood pressure but also in reducing kidney disease progression (particularly when associated with proteinuria) and cardiovascular events.Among RAS blocking agents, direct renin inhibitors have shown not only excellent efficacy in hypertension control but also pharmacologic tolerance that is comparable with other reninangiotensin suppressors. Indeed, aliskiren, the only direct renin inhibitor available is effective in controlling blood pressure as monotherapy or in combination with other antihypertensive drugs, irrespective of patient's age, ethnicity or sex. It is also effective in patients with metabolic syndrome, obesity and diabetes. Long-term studies comparing 'hard endpoints' of aliskiren therapy versus treatment with other RAS inhibitors, including cardiac and kidney protection, are currently ongoing. Combined with other antihypertensive agents, aliskiren not only improves their hypotensive response but may also lessen the adverse effects of other drugs. In high-risk patients, however, precautions should be taken when combining two or more renin-angiotensin inhibiting agents, as tissue perfusion may be highly renin-dependent in these patients and serious adverse side effects could take place.

show abstract

The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

Cited by 111 publications

References 31 publications

Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice

Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice

Active Vitamin D Treatment for Reduction of Residual Proteinuria

Direct renin inhibition: extricating facts from façades

Contact Info

Product

Resources

About