Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial

Uzu, Takashi; Araki, Shin‐ichi; Kashiwagi, Atsunori; Haneda, Masakazu; Koya, Daisuke; Yokoyama, Hiroyuki; Kida, Yasuo; Ikebuchi, Motoyoshi; Nakamura, Takaaki; Nishimura, Masataka; Takahara, Noriko; Obata, Toshiyuki; Omichi, Nobuyuki; Sakamoto, Katsuhiko; Shingu, Ryosuke; Taki, Hideki; Nagai, Yoshio; Tokuda, Hiroaki; Kitada, Munehiro; Misawa, Miwa; Nishiyama, Akira; Kobori, Hiroyuki; Maegawa, Hiroshi

doi:10.1371/journal.pone.0164936

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…Studies have shown that the use of ACE-i/ARB suppresses both plasma and intrarenal RAS activation ( 24 , 25 ). However, approximately 5%–20% of patients treated with ACE inhibitors cannot tolerate these drugs because of dry cough, angioedema, hypotension, hyperkalemia, or renal dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Relationship between intrarenal renin-angiotensin activity and re-hospitalization in patients with heart failure with reduced ejection fraction

Örsçelik¹

2018

Anatol J Cardiol

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ObjectiveHeart failure (HF) is a clinical syndrome resulting from structural or functional damages. Although clinical trials have shown that the plasma renin–angiotensin system (RAS) activation decreases HF functional status and increases hospitalization for HF patients, the effect of intrarenal RAS activity is still unknown. In this study, we investigated the relationship between the New York Heart Association (NYHA) class, duration, and number of hospitalizations in the previous year and urinary angiotensinogen (UAGT) in patients with HF with reduced ejection fraction (HFrEF).MethodsThis study included 85 patients who had an ejection fraction of <40% and were receiving optimal medical treatment. Among these, 22 were excluded from the study for various reasons. Demographically and biochemically, the remaining 63 patients were compared according to the NYHA functional classes and re-hospitalization status.ResultsWhen the groups were compared in terms of N-terminal pro–B-type natriuretic peptide (NT-proBNP), UAGT, and high-sensitivity C-reactive protein (Hs-CRP), it was found that these parameters were significantly higher in patients who were hospitalized more than two times in the previous year [p<0.001; p=0.007; p<0.001, respectively]. There was a significant correlation between number of hospitalizations and NT-proBNP (r=0.507, p<0.001), Hs-CRP (r=0.511, p<0.001), hemoglobin (r=-0.419, p=0.001), serum sodium (r=-0.26, p=0.04), and systolic blood pressure (r=-0.283, p=0.02). When the independence of multiple correlations was assessed using multiple linear regression analysis, NT-proBNP, Hs-CRP, and hemoglobin levels were independent predictors of re-hospitalization, but this was not the same for UAGT.ConclusionAlthough UAGT levels are high in patients with poor NYHA functional class and repeated hospitalizations, this marker is not valuable for predicting repeated hospitalization in patients with HFrEF. (Anatol J Cardiol 2018; 19: 205-12)

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Section: Discussionmentioning

confidence: 99%

Relationship between intrarenal renin-angiotensin activity and re-hospitalization in patients with heart failure with reduced ejection fraction

Örsçelik¹

2018

Anatol J Cardiol

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“…Table 1 shows the characteristics of the included studies and participants. Of all the included studies, two compared the monotherapy of direct renin inhibitors with angiotensin receptor blocker (ARB) [11,13], while two studies compared the combination of direct renin inhibitors with monotherapy of ARB or angiotensin-converting enzyme inhibitor (ACEI) [9,12]. The dose for ARB, ACEI and direct renin inhibitors varied in the included study.…”

Section: Resultsmentioning

confidence: 99%

“…It is well recognized that one of the most effective therapeutic approaches for lowering the risk of cardiovascular and renal events in diabetic patients is to treat microalbuminuria by blocking the renin-angiotensin-aldosterone pathway [ 13 ]. In the present meta-analysis, direct renin inhibitor was associated with a significant reduction in UACR and also improvement in other outcomes including remission from microalbuminuria to normal albuminuria and progression from microalbuminuria to macroalbuminuria.…”

Section: Reviewmentioning

confidence: 99%

Efficacy of Direct Renin Inhibitors in Slowing Down the Progression of Diabetic Kidney Disease: A Meta-Analysis

Akbariromani¹,

Haseeb²,

Nazly³

et al. 2022

Cureus

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Albuminuria is a risk factor for chronic kidney disease and cardiovascular events in diabetic people. The pathogenic processes in these circumstances have been documented to be significantly influenced by enhanced renin-angiotensin system activity. The current meta-analysis was carried out to assess the efficacy of direct renin inhibitors in preventing the progression of diabetic kidney disease. This metaanalysis was conducted as per the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched the relevant medical literature through PubMed, Cochrane library and EMBASE. The primary efficacy outcome was a percentage change in urine albumin-creatinine ratio (UACR) (in mg/g) level. Other primary efficacy outcomes included remission from microalbuminuria to normal albuminuria and progression from microalbuminuria to macroalbuminuria. Four randomized control studies were identified and included in the current meta-analysis involving 9,609 participants. The use of direct renin inhibitors was superior in reducing mean UACR compared to angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. The pooled mean difference in UACR between direct renin inhibitors and the control group was 9.42% (95% CI: -15.70 to -3.15: p-value=0.003). The odds of progression from microalbuminuria to normal albuminuria are 1.26 times higher in patients receiving direct renin inhibitors compared to patients in the control group (OR: 1.26, 95% CI: 1.08-1.46, p-value=0.002). The odds of remission from microalbuminuria to macroalbuminuria were 20% lower in patients receiving direct renin inhibitors compared to patients in the control group (OR: 0.80, 95% CI: 0.69-0.93, p-value=0.003). The use of aliskiren is associated with a significant reduction in UACR, increased remission from microalbuminuria to normal albuminuria and decreased progression from microalbuminuria to macroalbuminuria.

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“…In contrast, there are also a number of studies (n = 21) which investigated the effect of using monotherapies, and report some benefits and effects on renal outcomes and/or RAAS blockade efficacy among DN patients [16][17][18][19]21,24,[26][27][28][29][30][31]33,38,40,46,47,53,[57][58][59].…”

Section: Discussionmentioning

confidence: 99%

“…However, these studies do not report significant benefits of these therapies when used in combination. ARBs have also shown to be a more superior and potent treatment option compared to others among DN patients [16,30]. In six studies, the therapies appeared to have a similar effect or were unable to show any effect or benefit on varied renal outcomes [1,20,23,25,36,44].…”

Section: Discussionmentioning

confidence: 99%

A Dose Response Analysis of Dual Renin Angiotensin Aldosterone System (RAAS) Blockade Among Diabetic Nephropathy Patients with Albuminuria and Proteinuria: A Meta-Analysis

Dalbhi¹,

Eissa²,

Kayid³

et al. 2019

Diabetes Complications

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Objective: Treatment with renin angiotensin aldosterone system (RAAS) blockade including angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) have been shown to improve clinical outcomes. However, recent contrasting evidence regarding the dual RAAS blockade has also been presented. Very few studies have investigated the effectiveness of this dual blockade among diabetic nephropathy (DN) patients in association with albuminuria or proteinuria. Research Design and Methods: A review of randomized controlled trial (RCT) studies (n=45) reporting on the dose response analysis among DN patients using the RAAS blockade (including both ACEi and ARBs and other combinations) and other monotherapies over a 25-year period was performed. Overall, 45 studies of DN patients (n=18,628) with albuminuria or proteinuria were included. Results: An association between dual RAAS blockade and DN was observed, in which 18 of the 45 datasets revealed that combination therapies were effective among DN patients. Although there was a decline in albuminuria (mean difference:-19.93 mcg/L; 95% CI-50.32-10.47; I2 = 87.8%, p = 0.000) and a slight decline in proteinuria (mean difference:-0.19 mg/mmol; 95% CI-2.32-2.70; I2 = 99.2%, p = 0.000) with dual RAAS blockade combination therapy, these results demonstrated high heterogeneity among studies, with non-significant effects. Conclusion: Based on this study, it appears that dual RAAS blockade (or a combination of therapies) is a neutral treatment for patients with DN presenting with symptoms of albuminuria and/or proteinuria. Therefore, other factors must be considered when recommending therapies for DN patients.

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Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial

Cited by 12 publications

References 23 publications

Relationship between intrarenal renin-angiotensin activity and re-hospitalization in patients with heart failure with reduced ejection fraction

Relationship between intrarenal renin-angiotensin activity and re-hospitalization in patients with heart failure with reduced ejection fraction

Efficacy of Direct Renin Inhibitors in Slowing Down the Progression of Diabetic Kidney Disease: A Meta-Analysis

A Dose Response Analysis of Dual Renin Angiotensin Aldosterone System (RAAS) Blockade Among Diabetic Nephropathy Patients with Albuminuria and Proteinuria: A Meta-Analysis

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