Renin-Angiotensin-Aldosterone system blockade in diabetic kidney disease: A critical and contrarian point of view

Elrggal, Mohamed E; Ahmed, Shaaban M. S.; Nahas, Meguid El

doi:10.4103/1319-2442.194583

Cited by 5 publications

(5 citation statements)

References 2 publications

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“…On the other hand, for patients with CKD, hypertension, diabetes, and no albuminuria, current evidence does not support clear clinical benefits of RAASi for CKD progression, and other antihypertensive drugs are appropriate for BP management; however, the Kidney Disease Improving Global Outcomes guidelines (KDIGO) stated that these patients may be preferably treated with RAASi (ACEi or ARB), given the cardiovascular (CV) protection benefits, especially in patients with a higher glomerular filtration rate (GFR)1. There has been some criticism about the superiority of RAS inhibitors compared to other hypertensive agents in albuminuric patients [11], but generally, the presence of protein should be considered an indication for the use of ACEi or ARB.…”

Section: Angiotensin Converting Enzyme Inhibitors and Angiotensin-rec...mentioning

confidence: 99%

Management of Hypertension in Diabetic Kidney Disease

Colbert,

Elrggal,

Gaddy

et al. 2023

JCM

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Hypertension is a critical component of cardiovascular disease progression in patients with chronic kidney disease, and specifically diabetic kidney disease (DKD). Causation versus correlation remains up for debate, but what has been confirmed is the delay of DKD progression when hypertension is controlled or moved to guideline drive ranges. Many medications have been studied and used in real world experience for best outcomes, and we discuss below the proven winners thus far making up the renin angiotensin aldosterone system. As well, we discuss guideline changing medications including sodium-glucose cotransporter 2 inhibitors and newer generation mineralocorticoid receptor antagonists. With the growing prevalence of diabetes and DKD in the population, newer agents are emerging in multiple drug class and will be highlighted below. Clinicians continue to search for the optimal care plans for this challenging patient population.

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Section: Angiotensin Converting Enzyme Inhibitors and Angiotensin-rec...mentioning

confidence: 99%

Management of Hypertension in Diabetic Kidney Disease

Colbert,

Elrggal,

Gaddy

et al. 2023

JCM

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“…This is because they were heterogeneous studies with short follow-up durations and weak end-points [10]. Although a study conducted by Elrggal et al was selective and somewhat biased, the authors make compelling arguments that cast serious doubt over the strength of the evidence upon which the current guidelines are based, favoring the use of dual RAAS blockade among DKD patients [11].…”

Section: Contrasting Evidence On the Dual Raas Blockadementioning

confidence: 99%

“…Regarding albuminuria, a few studies suggest that albuminuria should not be considered as a target for treatment, but instead a surrogate marker of DKD progression, as it is unknown whether the adverse effects of combination therapy will offset any benefit [11,12]. It was also suggested that reduced albuminuria does not always translate to a decrease in cardiovascular and renal morbidity.…”

Section: Contrasting Evidence On the Dual Raas Blockadementioning

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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“…Preventing progression to ESRD in patients with DKD requires, especially in the overt proteinuria period, prompt identification and management [ 3 ]. Randomized trials have demonstrated that renin-angiotensin-aldosterone system (RAAS) blockers can reduce albuminuria and the progression to renal failure in DKD [ 4 ]. Side effects of RAAS blocker agents, including angioedema, persistent cough, temporary increases in serum creatinine (SCr), compromise patients’ long-term compliance [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Chinese herbal medicine Shenzhuo Formula treatment in patients with macroalbuminuria secondary to diabetic kidney disease: study protocol for a randomized controlled trial

Zhao

Zhang

et al. 2018

Trials

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BackgroundDiabetic kidney disease (DKD) is a serious complication associated with diabetes mellitus and can cause end-stage renal disease (ESRD). Traditional Chinese medicine (TCM) is widely used in China to treat DKD, and in particular microalbuminuria and macroalbuminuria. This study will address the efficacy and safety of Shenzhuo Formula (SZF), a frequently prescribed TCM, in DKD patients with macroalbuminuria.Methods/designThis study is a 24-week, randomized, multi-center, double-blinded, double-dummy, controlled, clinical trial that will include 120 DKD patients aged 18 to 80 years old with a 24-h urinary protein (24-h UP) level of between 0.5 g and 3 g and serum creatinine (SCr) ≤ 133 μmol/L (1.5 mg/dL) and compare SZF to irbesartan. The 24-h UP change from baseline to week 24 will represent the primary endpoint with secondary endpoints including SCr, estimated glomerular filtration rate (eGFR), TCM symptoms, urinary albumin excretion rate (UAER), etc. Safety assessments will also be evaluated.DiscussionThis study will provide initial evidence regarding the efficacy and safety of SZF relative to irbesartan in the treatment of DKD patients with macroalbuminuria.Trial registrationChinese Clinical Trial Registry, ID: ChiCTR-ICR-15006311. Registered on 15 April 2015.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2573-z) contains supplementary material, which is available to authorized users.

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Renin-Angiotensin-Aldosterone system blockade in diabetic kidney disease: A critical and contrarian point of view

Cited by 5 publications

References 2 publications

Management of Hypertension in Diabetic Kidney Disease

Management of Hypertension in Diabetic Kidney Disease

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

Chinese herbal medicine Shenzhuo Formula treatment in patients with macroalbuminuria secondary to diabetic kidney disease: study protocol for a randomized controlled trial

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