Recurrent hyperkalaemia management and use of renin-angiotensin-aldosterone system inhibitors: a European multi-national targeted chart review.
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ABSTRACT:
SUBMITTER: Rossignol P
PROVIDER: S-EPMC7467623 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Recurrent hyperkalaemia management and use of renin-angiotensin-aldosterone system inhibitors: a European multi-national targeted chart review.
Rossignol Patrick P Ruilope Luis M LM Cupisti Adamasco A Ketteler Markus M Wheeler David C DC Pignot Marc M Cornea Georgiana G Schulmann Thierry T Lund Lars H LH
Clinical kidney journal 20190930 4
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Project description:Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure (HF) patients due to the disease itself, which often co-exists with chronic kidney disease and diabetes mellitus, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. In particular, hyperkalaemia opposes to their administration or up-titration, thus impacting on mortality. New K+ binders, namely, patiromer and sodium zirconium cyclosilicate, are an intriguing option to manage hyperkalaemia in HF patients, both to reduce its fatal effects and to let clinicians up-titrate RAAS inhibitors. Even if their real impact on strong outcomes is still to be determined, we hereby provide an overview of hyperkalaemia in HF and its current management. New trials are welcome to fill the gap in knowledge.
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Project description:Purpose of reviewThis review summarises the literature data and provides an overview of the role and impact of the use of renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with coronavirus disease 2019 (COVID-19) infection.Recent findingsThe angiotensin-converting enzyme 2 (ACE2) has a key role in the regulation of the RAAS pathway, downregulating angiotensin II and attenuating inflammation, vasoconstriction and oxidative stress. Additionally, it plays an instrumental part in COVID-19 infection as it facilitates the cell entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enables its replication. The use and role of RAAS inhibitors therefore during the COVID-19 pandemic have been intensively investigated. Although it was initially assumed that RAAS inhibitors may relate to worse clinical outcomes and severe disease, data from large studies and meta-analyses demonstrated that they do not have an adverse impact on clinical outcomes or prognosis. On the contrary, some experimental and retrospective observational cohort studies showed a potential protective mechanism, although this effect remains to be seen in large clinical trials.
| S-EPMC9206216 | biostudies-literature
Project description:Chronic activation of the renin-angiotensin-aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro-fibrotic, -inflammatory, and -hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.
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Project description:With the multiplication of COVID-19 severe acute respiratory syndrome cases due to SARS-COV2, some concerns about angiotensin-converting enzyme 1 (ACE1) inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARB) have emerged. Since the ACE2 (angiotensin-converting enzyme 2) enzyme is the receptor that allows SARS COV2 entry into cells, the fear was that pre-existing treatment with ACEi or ARB might increase the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection. The present article discusses these concerns. ACE2 is a membrane-bound enzyme (carboxypeptidase) that contributes to the inactivation of angiotensin II and therefore physiologically counters angiotensin II effects. ACEis do not inhibit ACE2. Although ARBs have been shown to up-regulate ACE2 tissue expression in experimental animals, evidence was not always consistent in human studies. Moreover, to date there is no evidence that ACEi or ARB administration facilitates SARS-COV2 cell entry by increasing ACE2 tissue expression in either animal or human studies. Finally, some studies support the hypothesis that elevated ACE2 membrane expression and tissue activity by administration of ARB and/or infusion of soluble ACE2 could confer protective properties against inflammatory tissue damage in COVID-19 infection. In summary, based on the currently available evidence and as advocated by many medical societies, ACEi or ARB should not be discontinued because of concerns with COVID-19 infection, except when the hemodynamic situation is precarious and case-by-case adjustment is required.
| S-EPMC7172808 | biostudies-literature
Project description:The renin-angiotensin-aldosterone system (RAAS) is not the sole, but perhaps the most important volume regulator in vertebrates. To gain insights into the function and evolution of its components, we conducted a phylogenetic analysis of its main related genes. We found that important parts of the system began to appear with primitive chordates and tunicates and that all major components were present at the divergence of bony fish, with the exception of the Mas receptor. The Mas receptor first appears after the bony-fish/tetrapod divergence. This phase of evolutionary innovation happened about 400 million years ago. We found solid evidence that angiotensinogen made its appearance in cartilage fish. The presence of several RAAS genes in organisms that lack all the components shows that these genes have had other ancestral functions outside of their current role. Our analysis underscores the utility of sequence comparisons in the study of evolution. Such analyses may provide new hypotheses as to how and why in today's population an increased activity of the RAAS frequently leads to faulty salt and volume regulation, hypertension, and cardiovascular diseases, opening up new and clinically important research areas for evolutionary medicine.
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Project description:The role of the renin-angiotensin-aldosterone system (RAAS) in many cardiovascular disorders, including hypertension, cardiac hypertrophy, and atherosclerosis, is well established, whereas its relationship with cardiac arrhythmias is a new area of investigation. Atrial fibrillation and malignant ventricular tachyarrhythmias, especially in the setting of cardiac hypertrophy or failure, seem to be examples of RAAS-related arrhythmias because treatment with RAAS modulators, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor blockers, reduces the incidence of these arrhythmias. RAAS has a multitude of electrophysiological effects and can potentially cause arrhythmia through a variety of mechanisms. We review new experimental results that suggest that RAAS has proarrhythmic effects on membrane and sarcoplasmic reticulum ion channels and that increased oxidative stress is likely contributing to the increased arrhythmic incidence. A summary of ongoing clinical trials that will address the clinical usefulness of RAAS modulators for prevention or treatment of arrhythmias is presented.
| S-EPMC2600881 | biostudies-literature
Project description:AimsThe aims of this study were to evaluate if the risk of cardiovascular events and all-cause mortality was higher in the presence of hyperkalaemia (HK) in patients with heart failure (HF) treated with renin-angiotensin-aldosterone system inhibitors (RAASi), and to investigate in this cohort the increased risk of cardiovascular events and all-cause mortality among HK patients with non-optimal adherence to RAASi therapy.Methods and resultsIn this retrospective cohort study based on administrative databases of five Italian Local Health Units, all adult patients with a HF diagnosis between January 2010 and December 2017 were included only if they were prescribed RAASi therapy during the first 3 months after the index date, that corresponded to the date of first HF diagnosis during the inclusion period. Patients were considered to have HK if serum potassium level was ≥5.5 mmol/L. A propensity score matching was applied before evaluation of hazard ratios. Patients with HK were 37% (P < 0.001) and 70% (P < 0.001), respectively, more at risk of cardiovascular events and of dying for all-cause mortality compared to non-HK patients. Among the HK group, patients non-adherent to RAASi therapy had a 39% (P = 0.105) higher risk of cardiovascular events and a twofold increased risk (P < 0.001) of all-cause death.ConclusionFindings from this real-world study showed that in a cohort of HF patients under RAASi therapy, subjects with HK had an enhanced risk of cardiovascular events or death compared to patients without HK. Moreover, in HK patients, sub-optimal adherence to RAASi therapy was associated with an increased risk of all-cause mortality.
| S-EPMC7756371 | biostudies-literature
Project description:AimsIn patients with current or a history of hyperkalaemia, treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K+ ) binder, may improve serum K+ levels and adherence to RAASi.MethodsThe DIAMOND trial will enroll ∼820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction ≤40%). Patients meeting the screening criteria will enter a single-blinded run-in phase where they will be started or continued on a mineralocorticoid receptor antagonist (MRA) titrated to 50 mg/day and other RAASi therapy to ≥50% target dose, and patiromer. Patiromer will be titrated up to a maximum three packs/day (8.4 g/pack) to achieve optimal doses of RAASi without hyperkalaemia. The run-in phase will last up to 12 weeks, following which patients will undergo double-blind randomization in a 1:1 ratio to receive either continued patiromer or placebo (patiromer withdrawal). The primary endpoint is the mean difference in serum K+ from randomization between patiromer and placebo arms. Secondary endpoints will include hyperkalaemia events with K+ value >5.5 mEq/L, durable enablement of MRA at target dose, investigator-reported adverse events of hyperkalaemia, hyperkalaemia-related clinical endpoints and an overall RAASi use score (using a 0-8-point scale) comprising all-cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication.ConclusionThe DIAMOND trial is designed to determine if patiromer can favourably impact K+ control in patients with HFrEF with hyperkalaemia or a history of hyperkalaemia leading to RAASi therapy compromise, and in turn improve RAASi use.
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Project description:Because adult podocytes cannot proliferate and are therefore unable to self-renew, replacement of these cells depends on stem/progenitor cells. Although podocyte number is higher after renin-angiotensin-aldosterone system (RAAS) inhibition in glomerular diseases, the events explaining this increase are unclear. Cells of renin lineage (CoRL) have marked plasticity, including the ability to acquire a podocyte phenotype. To test the hypothesis that RAAS inhibition partially replenishes adult podocytes by increasing CoRL number, migration, and/or transdifferentiation, we administered tamoxifen to Ren1cCreERxRs-tdTomato-R CoRL reporter mice to induce permanent labeling of CoRL with red fluorescent protein variant tdTomato. We then induced experimental FSGS, typified by abrupt podocyte depletion, with a cytopathic antipodocyte antibody. RAAS inhibition by enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin-receptor blocker) in FSGS mice stimulated the proliferation of CoRL, increasing the reservoir of these cells in the juxtaglomerular compartment (JGC). Compared with water or hydralazine, RAAS inhibition significantly increased the migration of CoRL from the JGC to the intraglomerular compartment (IGC), with more glomeruli containing RFP+CoRL and, within these glomeruli, more RFP+CoRL. Moreover, RAAS inhibition in FSGS mice increased RFP+CoRL transdifferentiation in the IGC to phenotypes, consistent with those of podocytes (coexpression of synaptopodin and Wilms tumor protein), parietal epithelial cells (PAX 8), and mesangial cells (α8 integrin). These results show that in the context of podocyte depletion in FSGS, RAAS inhibition augments CoRL proliferation and plasticity toward three different glomerular cell lineages.
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