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Estimating the risk of acute kidney injury associated with use of diuretics and renin angiotensin aldosterone system inhibitors: A population based cohort study using the clinical practice research datalink.

ABSTRACT: BACKGROUND:The risk of acute kidney injury (AKI) attributable to renin angiotensin aldosterone (RAAS) inhibitors and diuretics remains unclear. METHODS:We conducted a prospective cohort study using the Clinical Practice Research Datalink (2008-2015) linked to Hospital Episode Statistics - Admitted Patient Care and Office for National Statistics mortality data. Patients were included if they had one or more chronic diagnoses requiring medication. Exposed patients had a first ever prescription for RAAS inhibitors/diuretics during the study period. AKI risk associated with exposure was determined by multivariable Cox regression, propensity score-adjusted Cox regression and a prior event rate ratio (PERR) analysis. RESULTS:One hundred forty thousand nine hundred fifty-two individuals were included. Increased AKI risk in the exposed group was demonstrated in both the multivariable and propensity score-adjusted cox regressions (HR 1.23 (95% CI 1.04-1.45) and HR 1.24 (1.05-1.47) respectively). The PERR analysis provided a similar overall hazard ratio with a wider confidence interval (HR 1.29 (0.94-1.63)). The increased AKI risk in the exposed group was present only in those receiving two or more antihypertensives. Absolute AKI risk was small. CONCLUSIONS:RAAS inhibitors/diuretics result in an increased risk of AKI. The absolute increase in AKI risk is small, however, and needs to be considered in the context of any potential benefits.

SUBMITTER: Scott J

PROVIDER: S-EPMC6937998 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Lab monitoring and acute care utilization during initiation of renin angiotensin aldosterone inhibitors or diuretics in chronic kidney disease.

Project description:Renin angiotensin aldosterone system inhibitors (RAASi) and diuretics are among the most frequently prescribed anti-hypertensives. Individuals with chronic kidney disease (CKD) are particularly at risk for electrolyte disturbances and kidney injury but the appropriate use of lab monitoring following RAASi or diuretic initiation is uncertain in CKD.We describe the frequency and time interval of lab monitoring during initiation of RAASi and diuretics in CKD and assess whether close lab monitoring associates with one-year risk of emergency department (ED) visit or hospitalization.We evaluated an observational cohort of 8,217 individuals with stage 3-5 non-dialysis CKD newly prescribed a RAASi (52.3%) or diuretic (47.7%) from thirty-six primary care offices affiliated with Brigham and Women's Hospital and Massachusetts General Hospital between 2009 and 2011.Overall, 3306 (40.2%) individuals did not have pre-prescription labs done within 2 weeks, and 5957 (72.5%) did not have post-prescription labs done within 2 weeks which includes 524 (6.4%) individuals without post-prescription within 1 year. Close monitoring occurred in only 1547 (20.1%) and was more likely in individuals prescribed diuretics compared to RAASi (adjusted OR 1.39; 95%CI 1.20-1.62), with CKD stage 4,5 compared with stage 3 (adjusted OR 1.47; 95%CI 1.16-1.86) and with cardiovascular disease (adjusted OR 1.42; 95%CI 1.21-1.66). Close monitoring was not associated with decreased risk of ED visit or hospitalization.Close lab monitoring during initiation of RAASi or diuretics was more common in participants with cardiovascular disease and advanced CKD suggesting physicians selected high-risk individuals for close monitoring. As nearly 80% of individuals did not receive close lab monitoring there may be value in future research on electronic physician decision tools targeted at lab monitoring.

| S-EPMC6919529 | biostudies-literature

Renin-Angiotensin-Aldosterone Inhibitors and COVID-19 Infection.

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

Role of renin-angiotensin-aldosterone system inhibitors in heart failure and chronic kidney disease.

Project description:Renin-angiotensin-aldosterone system (RAAS) inhibitors are the key medications for patients with heart failure and chronic kidney disease. Multiple randomized controlled trials have demonstrated their benefits in an outpatient setting for the treatment of chronic heart failure. Additional advantages in acute heart failure treatment during inpatient hospitalization are less clear but a small number of non-randomized studies have favored their use. Conditions that result in stoppage of RAAS inhibitors during inpatient stay are an increase in serum creatinine, hyperkalemia, and hemodynamic instability such as hypotension. The role of RAAS inhibitors in chronic kidney disease has also been documented in multiple randomized controlled trials, with their use in hypertension and proteinuria being unambiguous. This narrative review summarizes the role of RAAS inhibitors in acute and chronic heart failure and chronic kidney disease.

| S-EPMC7673621 | biostudies-literature

Inhibitors of the Renin-Angiotensin-Aldosterone System and Covid-19.

Project description: Not available

| S-EPMC7224604 | biostudies-literature

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19.

Project description:BackgroundThere is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).MethodsWe assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference.ResultsAmong 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.ConclusionsWe found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

| S-EPMC7206932 | biostudies-literature

Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19.

Project description: Not available

| S-EPMC7121452 | biostudies-literature

Hyperkalemia and renin-angiotensin aldosterone system inhibitor therapy in chronic kidney disease: A general practice-based, observational study.

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

Renin-Angiotensin Aldosterone System Inhibitors in Primary Prevention and COVID-19.

Project description:Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin-angiotensin aldosterone system (RAAS) inhibitor use and COVID-19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID-19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine-learning-derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID-19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74-1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID-19 (HR, 0.92; 95% CI, 0.70-1.22), and 64 died with COVID-19 (HR, 1.22; 95% CI, 0.68-2.19). The severity of COVID-19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89-1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID-19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID-19 pandemic.

| S-EPMC8475700 | biostudies-literature

Role of the intrarenal renin-angiotensin-aldosterone system in chronic kidney disease.

Project description:The existence of local or tissue-based renin-angiotensin-aldosterone systems (RAAS) is well documented and has been implicated as a key player in the pathogenesis of cardiovascular and renal diseases. The kidney contains all elements of the RAAS, and intrarenal formation of angiotensin II not only controls glomerular hemodynamics and tubule sodium transport, but also activates a number of inflammatory and fibrotic pathways. Experimental and clinical studies have shown that the intrarenal RAAS is activated early in diabetic nephropathy, the leading cause of chronic kidney disease (CKD). Although angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the rate of decline in kidney function in patients with diabetic and non-diabetic nephropathy, many patients still progress to end-stage renal disease or die from cardiovascular events. There is still a clear need for additional strategies to block the RAAS more effectively to reduce progression of CKD. The focus of this paper is to review the importance of the intrarenal RAAS in CKD and recent findings in renin-angiotensin biology pertinent to the kidney. We also discuss additional strategies to inhibit the RAAS more effectively and the potential impact of direct renin inhibition on the prevention and management of CKD.

| S-EPMC3202956 | biostudies-literature

Adherence to long-term use of renin-angiotensin II-aldosterone system inhibitors in children with chronic kidney disease.

Project description:BackgroundAlthough renin-angiotensin II-aldosterone system inhibitor (RASI) use for renal protection is well-documented, adherence to RASI therapy in the pediatric population is unclear. This study aimed to evaluate patient characteristics associated with adherence to chronic RASI use in patients with childhood chronic kidney disease (CKD).MethodsChildhood CKD was identified using ICD-9 codes in the population-based, Taiwan national health insurance research database between 1997 and 2011. Patients continuously receiving RASIs for ≥3 months without interruption > 30 days after CKD diagnosis were defined as incident users. Medication adherence was measured as the proportion of days covered (PDC) by RASI prescription refills during the study period. Multivariate logistic regression was employed to assess the odds for adherence (PDC ≥80%) to RASI refills.ResultsOf 1271 incident users of RASI chronic therapy, 16.9% (n = 215) had PDC ≥80%. Compared to the group with PDC < 80%, patients in the high adherence group more often had proteinuria (aOR [adjusted odds ratio]1.93; 95%CI [confidence interval], 1.18-3.17), anemia (aOR, 1.76; 95% CI, 1.20-2.58), and time to start of chronic use > 2 years (aOR, 1.12; 95%CI, 1.06-1.19). Odds of being non-adherent were increased by hypertension and older ages (comparing to < 4 years) at start of chronic use, 9-12 years (aOR, 0.38; 95%CI, 0.17-0.82), 13-17 years (aOR, 0.45; 95%CI, 0.22-0.93),≥18 years (aOR, 0.34; 95%CI 0.16-0.72) and males (aOR, 0.68; 95%CI, 0.49-0.94).ConclusionsThe rate of RASI prescription refilling adherence was relatively low and associated with CKD-specific comorbid conditions. This study identifies factors associated with low adherence and highlights the need to identify those who should be targeted for intervention to achieve better blood pressure control, preventing CKD progression.

| S-EPMC6383266 | biostudies-literature

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