scholarly journals Targeting the Renin–Angiotensin–Aldosterone System to Prevent Hypertension and Kidney Disease of Developmental Origins

2021 ◽  
Vol 22 (5) ◽  
pp. 2298
Author(s):  
Chien-Ning Hsu ◽  
You-Lin Tain
Keyword(s):  
Kidney Disease ◽  
Current Knowledge ◽  
Current Evidence ◽  
Developmental Origins ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Health And Disease ◽  
Nitric Oxide Deficiency ◽  
Developing Kidney ◽  
Prevention Of Hypertension

The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease. The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood. This theory is known as developmental origins of health and disease (DOHaD). Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming. In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins. To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.

scholarly journals Gasotransmitters for the Therapeutic Prevention of Hypertension and Kidney Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 7808
Author(s):  
Chien-Ning Hsu ◽  
You-Lin Tain
Keyword(s):  
Nitric Oxide ◽  
Kidney Disease ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Current Evidence ◽  
Developmental Origins ◽  
Developing Kidney ◽  
Prevention Of Hypertension ◽  
Therapeutic Prevention ◽  
In Pregnancy

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), three major gasotransmitters, are involved in pleiotropic biofunctions. Research on their roles in hypertension and kidney disease has greatly expanded recently. The developing kidney can be programmed by various adverse in utero conditions by so-called renal programming, giving rise to hypertension and kidney disease in adulthood. Accordingly, early gasotransmitter-based interventions may have therapeutic potential to revoke programming processes, subsequently preventing hypertension and kidney disease of developmental origins. In this review, we describe the current knowledge of NO, CO, and H2S implicated in pregnancy, including in physiological and pathophysiological processes, highlighting their key roles in hypertension and kidney disease. We summarize current evidence of gasotransmitter-based interventions for prevention of hypertension and kidney disease in animal models. Continued study is required to assess the interplay among the gasotransmitters NO, CO, and H2S and renal programming, as well as a greater focus on further clinical translation.

scholarly journals Developmental Origins of Kidney Disease: Why Oxidative Stress Matters?

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 33
Author(s):  
Chien-Ning Hsu ◽  
You-Lin Tain
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Current Knowledge ◽  
Future Research ◽  
Antioxidant Systems ◽  
Developmental Origins ◽  
Adult Onset ◽  
Functional Changes ◽  
Health And Disease ◽  
Developing Kidney

The “developmental origins of health and disease” theory indicates that many adult-onset diseases can originate in the earliest stages of life. The developing kidney has emerged as being particularly vulnerable to adverse in utero conditions leading to morphological and functional changes, namely renal programming. Emerging evidence indicates oxidative stress, an imbalance between reactive oxygen/nitrogen species (ROS/RNS) and antioxidant systems, plays a pathogenetic role in the developmental programming of kidney disease. Conversely, perinatal use of antioxidants has been implemented to reverse programming processes and prevent adult-onset diseases. We have termed this reprogramming. The focus of this review is twofold: (1) To summarize the current knowledge on oxidative stress implicated in renal programming and kidney disease of developmental origins; and (2) to provide an overview of reprogramming effects of perinatal antioxidant therapy on renal programming and how this may prevent adult-onset kidney disease. Although early-life oxidative stress is implicated in mediating renal programming and adverse offspring renal outcomes, and animal models provide promising results to allow perinatal antioxidants applied as potential reprogramming interventions, it is still awaiting clinical translation. This presents exciting new challenges and areas for future research.

scholarly journals Renin-angiotensin-aldosterone system inhibitors – a realm of confusion in COVID-19

2021 ◽  
Vol 4 (Special2) ◽  
pp. 389-394
Author(s):  
Angela Madalina Lazar
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Current Knowledge ◽  
Angiotensin Receptor Blockers ◽  
Protective Effects ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Raas Inhibitors

Currently, there is a persisting dispute regarding the renin-angiotensin-aldosterone-system (RAAS) inhibitors' safety of use in COVID-19 pandemics. On one side, RAAS inhibitors appear to determine an overexpression of ACE2, the receptor of SARS-CoV-2. Therefore, they could increase the risk of SARS-CoV-2 infection and its degree of severity. On the other side, the discontinuation of RAAS leads to cardiovascular decompensation and has been discouraged by the major medical societies. Also, large-cohort studies report beneficial or at least neutral effects for the RAAS inhibitors in COVID-19 patients. Worldwide, millions of patients receive RAAS inhibitors for the treatment of hypertension and other important comorbidities. In this context, knowledge of the exact effect of these medications becomes of crucial significance. This paper aims to fill in a gap in the current knowledge and presents a putative mechanism by which RAAS inhibitor administration's beneficial results can be explained better. RAAS inhibitors can be beneficial, as they counteract the excessive detrimental activation of the classical angiotensin-converting enzyme (ACE) axis, decreasing the angiotensin II levels. The angiotensin receptor blockers (ARBs) increase the angiotensin II levels, while the angiotensin-converting enzyme inhibitors (ACEI) increase the angiotensin I levels; these substrates will compete with the SARS-CoV-2 for the ACE2 binding, decreasing the viral infectivity. In addition, following the RAAS inhibitors treatment, the up-regulated ACE2 will cleave these substrates (angiotensin I and II), particularly to angiotensin 1-7 that possesses vasodilator, protective effects.

Analysing the impact of a guideline for the use of new potassium binders for treatment of chronic hyperkalaemia to maximise inhibition of renin–angiotensin–aldosterone system (RAAS) within the general nephrology clinic?

2020 ◽  
Author(s):  
Priyank Patel ◽  
Andrew Frankel
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Ckd Stage ◽  
The Mean ◽  
Potassium Binders ◽  
The Impact ◽  
Chronic Use

Abstract Background Renin–angiotensin–aldosterone system (RAAS) inhibitors provide significant cardiorenal benefits with improved long-term outcomes for patients. This is most significant for patients receiving maximal RAAS inhibition, but some patients are unable to tolerate this therapy because of hyperkalaemia. Recently published National Institute for Health and Care Excellence (NICE) technology appraisal guidance recommended using sodium zirconium cyclosilicate (SZC) and patiromer for patients with chronic kidney disease (CKD) stage 3b to 5 or heart failure with reduced ejection fraction, who are not taking an optimised dosage of RAAS inhibitor because of hyperkalaemia. Objective Determine the impact of a locally produced guideline on effective implementation of NICE recommendation for use of SZC or patiromer to help maximise inhibition of the renin–angiotensin–aldosterone system within the general nephrology clinic. Methods A local guideline to practically support the implementation of recommendations made by NICE in the chronic use of new potassium binders was produced. One hundred sequential patients in a general nephrology clinic with non-immune chronic kidney disease (CKD 3 to 5) had their electronic records reviewed. Those with an indication for RAAS inhibition were identified. Results Of the 100 consecutive patients audited, 46 were female and 54 were male. The mean age of these patients was 64 and the mean estimated glomerular filtration rate (eGFR) was 33. Sixty-eight patients had an indication for being on RAAS inhibition with only 10 on maximal doses. Of the remaining 58 patients, 26 (45%) were limited by hyperkalaemia. Of these 26 patients, 12 of these patients (46%) had hyperkalaemia associated with an episode of acute kidney injury (AKI). Therefore, 14% of patients attending a general nephrology clinic were identified suitable for SZC and patiromer. Conclusions A significant proportion (14%) of unselected patients attending a general nephrology clinic were not on optimum RAAS inhibition due to hyperkalaemia. These patients would meet the criteria established within a working guideline for the implementation of the chronic use of SZC or patiromer and are likely to attain prognostic long-term benefit by using these new potassium binders to maximise RAAS inhibition. This analysis has implications for renal centres across the UK.

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