Recurrent Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Treatment: Stuck between a Rock and a Hard Place.
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ABSTRACT:
SUBMITTER: Bolanos JA
PROVIDER: S-EPMC8011015 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Recurrent Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Treatment: Stuck between a Rock and a Hard Place.
Bolaños Jonathan A JA Seliger Stephen L SL
Clinical journal of the American Society of Nephrology : CJASN 20210219 3
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Project description:Hyperkalemia is common in clinical practice and can be caused by medications used to treat cardiovascular diseases, particularly renin-angiotensin-aldosterone system inhibitors (RAASis). This narrative review discusses the epidemiology, etiology, and consequences of hyperkalemia, and recommends strategies for the prevention and management of hyperkalemia, mainly focusing on guideline recommendations, while recognizing the gaps or differences between the guidelines. Available evidence emphasizes the importance of healthcare professionals (HCPs) taking a proactive approach to hyperkalemia management by prioritizing patient identification and acknowledging that hyperkalemia is often a long-term condition requiring ongoing treatment. Given the risk of hyperkalemia during RAASi treatment, it is advisable to monitor serum potassium levels prior to initiating these treatments, and then regularly throughout treatment. If RAASi therapy is indicated in patients with cardiorenal disease, HCPs should first treat chronic hyperkalemia before reducing the dose or discontinuing RAASis, as reduction or interruption of RAASi treatment can increase the risk of adverse cardiovascular and renal outcomes or death. Moreover, management of hyperkalemia should involve the use of newer potassium binders, such as sodium zirconium cyclosilicate or patiromer, as these agents can effectively enable optimal RAASi treatment. Finally, patients should receive education regarding hyperkalemia, the risks of discontinuing their current treatments, and need to avoid excessive dietary potassium intake.
| S-EPMC10954964 | biostudies-literature
Project description:Background: Whether to continue renin−angiotensin−aldosterone system inhibitor (RAASi) therapy in patients with hyperkalemia remains a clinical challenge, particularly in patients with heart failure (HF), where RAASis remain the cornerstone of treatment. We investigated the incidence of dose reduction or the cessation of RAASis and evaluated the threshold of serum potassium at which cessation alters the risk−benefit balance. Methods: This retrospective analysis of a Japanese nationwide claims database investigated treatment patterns of RAASis over 12 months after the initial hyperkalemic episode. The incidences of the clinical outcomes of patients with RAASi (all ACEi/ARB/MRA) or MRA-only cessation (vs. non-cessation) were compared via propensity score-matched patients. A cubic spline regression analysis assessed the hazard of death resulting from treatment cessation vs. no cessation at each potassium level. Results: A total of 5059 hyperkalemic HF patients were identified; most received low to moderate doses of ACEis and ARBs (86.9% and 71.5%, respectively) and low doses of MRAs (76.2%). The RAASi and MRA cessation rates were 34.7% and 52.8% at 1 year post-diagnosis, while the dose reduction rates were 8.4% and 6.5%, respectively. During the mean follow-up of 2.8 years, patients who ceased RAASi or MRA therapies were at higher risk for adverse outcomes; cubic spline analysis found that serum potassium levels of <5.9 and <5.7 mmol/L conferred an increased mortality risk for RAASi and MRA cessation, respectively. Conclusions: Treatment cessation/dose reduction of RAASis are common among HF patients. The risks of RAASi/MRA cessation may outweigh the benefits in patients with mild to moderate hyperkalemia.
| S-EPMC9572691 | biostudies-literature
Project description:IntroductionDiscontinuation of renin-angiotensin-aldosterone system inhibitor (RAASi) is common after hyperkalemia. We evaluated the risk of kidney and mortality outcomes associated with RAASi discontinuation among patients with chronic kidney disease (CKD) and hyperkalemia.MethodsWe identified adult patients with CKD (eGFR <60 mL/min/1.73 m2) who experienced new-onset hyperkalemia (potassium ≥5.0 mEq/L) between 2016 and 2017 from Kaiser Permanente Southern California and followed them through 2019. We defined treatment discontinuation as having ≥90-day gap in refills of all RAASi within 3 months after hyperkalemia. We used multivariable Cox proportional hazards models to evaluate the association between RAASi discontinuation and the primary composite outcome of kidney (≥40% eGFR decline, dialysis, kidney transplant) or all-cause mortality. We evaluated cardiovascular events and recurrence of hyperkalemia as secondary outcomes.ResultsAmong 5,728 patients (mean age 76 years), 13.5% discontinued RAASi within 3 months after new-onset hyperkalemia. During the median 2 years of follow-up, 29.7% had the primary composite outcome (15.5% with ≥40% eGFR decline, 2.8% dialysis or kidney transplant, 18.4% all-cause mortality). Patients who discontinued RAASi had a higher all-cause mortality compared with those who continued RAASi (26.7% vs. 17.1%) but had no differences in kidney outcomes, cardiovascular events, and recurrence of hyperkalemia. RAASi discontinuation was associated with a higher risk of kidney or all-cause mortality composite outcome (adjusted hazard ratio [aHR] 1.21, 95% CI: 1.06, 1.37) mainly driven by all-cause mortality (aHR: 1.34, 95% CI: 1.14, 1.56).ConclusionRAASi discontinuation after hyperkalemia was associated with worsened mortality, which may underscore the benefits of continuing RAASi among patients with CKD.
| S-EPMC10623389 | biostudies-literature
Project description:Renin-angiotensin-aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66-72 years; congestive heart failure [CHF] in 11%-19%; diabetes in 43%-54%; serum potassium ≥5 in 20%-35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had diabetes, hypertension, or less advanced CKD. In conclusion, RAASi prescription patterns vary by country, and by demographic and clinical characteristics. RAASi appear to be underused, even among patients with strong class-specific recommendations. Although the reasons for this variation could not be fully identified in this cross-sectional observation, our data indicate that the risk of hyperkalemia may contribute to the underuse of this class of agents in moderate to advanced CKD.
| S-EPMC6771881 | biostudies-literature
Project description:Data on hyperkalemia frequency among chronic kidney disease (CKD) patients receiving renin-angiotensin aldosterone system inhibitors (RAASis) and its impact on subsequent RAASi treatment are limited. This population-based cohort study sought to assess the incidence of clinically significant hyperkalemia among adult CKD patients who were prescribed a RAASi and the proportion of patients with RAASi medication change after experiencing incident hyperkalemia. We conducted a retrospective, population-based cohort study (1 January 2013-30 June 2017) using Australian national general practice data from the NPS MedicineWise's MedicineInsight program. The study included adults aged ≥18 years who received ≥1 RAASi prescription during the study period and had CKD (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73m2). Study outcomes included incident clinically significant hyperkalemia (serum potassium >6 mmol/L or a record of hyperkalemia diagnosis) and among patients who experienced incident hyperkalemia, the proportion who had RAASi medication changes (cessation or dose reduction during the 210-day period after the incident hyperkalemia event). Among 20,184 CKD patients with a median follow-up of 3.9 years, 1,992 (9.9%) patients experienced an episode of hyperkalemia. The overall incidence rate was 3.1 (95% CI: 2.9-3.2) per 100 person-years. Rates progressively increased with worsening eGFR (e.g. 3.5-fold increase in patients with eGFR <15 vs. 45-59 ml/min/1.73m2). Among patients who experienced incident hyperkalemia, 46.6% had changes made to their RAASi treatment regimen following the first occurrence of hyperkalemia (discontinuation: 36.6% and dose reduction: 10.0%). In this analysis of adult RAASi users with CKD, hyperkalemia and subsequent RAASi treatment changes were common. Further assessment of strategies for hyperkalemia management and optimal RAASi use among people with CKD are warranted.
| S-EPMC6405190 | biostudies-literature
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.
| S-EPMC6430926 | biostudies-literature
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:IntroductionHyperkalemia (HK) may result in disruptions of guidelines-concordant renin-angiotensin-aldosterone system inhibitors (RAASi), a standard of care in persons with chronic kidney disease (CKD). Such disruptions-dose reduction or discontinuation-diminish the benefits of RAASi, placing patients at risk of serious events and renal dysfunction. This real-world study evaluated RAASi modifications among patients who initiated sodium zirconium cyclosilicate (SZC) for HK.MethodsAdults (≥ 18 years) initiating outpatient SZC (index date) while on RAASi were identified from a large US claims database (January 2018-June 2020). RAASi optimization (maintain same or up-titration of RAASi dosage), non-optimization (down-titration of RAASi dosage or discontinuation), and persistence were descriptively summarized following index. Predictors of RAASi optimization were assessed using multivariable logistic regression models. Analyses were conducted by subgroups, including patients without end-stage kidney disease (ESKD), with CKD, and with CKD + diabetes.ResultsA total of 589 patients initiated SZC during RAASi therapy (mean age 61.0 years, 65.2% male), and 82.7% patients (n = 487) kept RAASi after index (mean follow-up = 8.1 months). Most patients (77.4%) optimized RAASi therapy after initiating SZC; 69.6% maintained the same dosage while 7.8% had up-titrations. A similar rate of RAASi optimization was observed among subgroups without ESKD (78.4%), with CKD (78.9%), and with CKD + diabetes (78.1%). At 1-year post-index, 73.9% of all patients who optimized RAASi were still on therapy, while only 17.9% of patients who did not optimize therapy were still on a RAASi. Among all patients, predictors of RAASi optimization included fewer prior hospitalizations (odds ratio = 0.79, 95% CI [0.63-1.00]; p < 0.05) and fewer prior emergency department (ED) visits (0.78 [0.63-0.96]; p < 0.05).ConclusionConsistent with clinical trial findings, nearly 80% of patients who initiated SZC for HK optimized their RAASi therapy. Patients may require long-term SZC therapy to encourage continuation of RAASi therapy especially after inpatient and ED visits.
| S-EPMC10220114 | 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.
| S-EPMC3354321 | biostudies-literature