Renin Angiotensin Aldosterone Research Articles

#1395 Management of CKD patients and HK, as its main complication: degree of adoption of the multi-society consensus on CKD and HK in Spain

Abstract Background and Aims The high incidence, morbidity and mortality of Chronic Kidney Disease (CKD) makes it a public health problem, due to the difficulties in its early detection and management. Hyperkalemia (HK) is a common complication of CKD, also associated with high morbidity and mortality, impacting on the management of patients with CKD and leading sometimes to deoptimization of their treatment. It has been shown that the development of multidisciplinary consensus contributes to improving patient management. With this objective, the multi-society consensus documents –Information and consensus document for the detection and management of chronic kidney disease (2022)- and –Recommendations for the management of hyperkalemia in the emergency department (2022)- have been published. The aim of this study is to analyze the degree of adoption of the recommendations of both consensus in clinical practice in Spain, in order to identify potential areas of improvement in the management of CKD patients with HK. Method This study is based on the perceptions obtained through the discussion on the applicability of the national consensus documents for the management of CKD and HK. To this end, two medical education programs focused on CKD and HK, respectively, were carried out to discuss the applicability of both consensuses. In total, 41 meetings were held (14 from ERC and 27 from HK) from April 2022 to April 2023, involving a total of 542 healthcare professionals (HCPs) (nephrologists and emergency physicians). The main hypothesis was that neither the consensuses are being followed regularly in Spanish clinical practice. All responses were coded numerically, and a national mean was created based on the meeting means. Results The majority of nephrologists who participated in the discussion of the consensus analysis consider that CKD is underdiagnosed (77%), and that the detection of albuminuria is not routinely performed in Primary Care (PC) (72%). Furthermore, half of the nephrologists point out that referrals from PC do not meet the recommended criteria. In relation to treatment, almost 90% of nephrologists would follow the recommendations for the use of RAASi (renin angiotensin aldosterone system inhibitors) and Dapagliflozin very frequently. Regarding HK (a complication of CKD), 42% of HCPs considered that 30-40% of patients with CKD and/or HF suffered a second episode of HK. In relation to its management, only 21% of HCPs considered that the recommendations to maintain treatment with RAASis were followed. Of those who modified it, more than 50% did not consider reintroducing it or considered it little. 33% of HCPs did not show willingness to use the new antihyperkalemia treatments upon discharge. 50% of the participants said they did not have access to them. Regarding follow-up, 54% considered that it should be done by PC specialists. Conclusion The recommendations specified in the CKD and HK management consensuses are being applied less than desired in Spanish clinical practice. Especially highlighting the lack of detection of albuminuria and non-compliance with the referral criteria in patients with CKD, which is consistent with the high underdiagnosis described in Spain. Furthermore, the recommendation of not to modifying the RAASi treatment for the management of HK is not regularly adopted, despite of its impact on the morbidity and mortality of these patients. This information could help to guide future interventions that aim to improve the diagnosis and management of patients with CKD and/or HK.

#1609 Effect of dapagliflozin in proteinuria reduction and glomerular filtration rate in a group of Alport syndrome patients

Abstract Background and Aims Alport syndrome (AS) is the most common cause of inherited chronic kidney disease. This disorder is caused by deleterious variants on COL4A3, COL4A4 or COL4A5 genes. These genes codify the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). Alterations in any of collagen type IV constituents cause disruption of the GMB structure, allowing the leakage of red blood cells and proteins, mainly albumin, into the urine resulting in kidney damage and loss of renal function. In AS progressive kidney impairment can be delayed or possibly prevented by timely initiation of renin angiotensin aldosterone inhibitors (RAAi): in males with X-linked AS and in autosomal recessive AS ARAS at diagnosis and in females with XLAS and autosomal dominant AS at the onset of microalbuminuria. Recently, it was showed that sodium-cotransporter-2 inhibitors (SGLT2i) reduce proteinuria and slow the progression of kidney disease in many glomerular diseases. Thus, also in AS, SGLT2i could be promising in renal disease progression control. The aim of this study was to determine the proteinuria reduction and the effect on the glomerular filtration rate (GFR) in a group of AS patients with persistent proteinuria besides the use of RAAi in maximum tolerated doses after adding SGLT2i to the treatment. Method This study was single-center, observational and prospective study evolving 8 AS adult patients, without a diagnosis of diabetes, with persistent proteinuria besides the use of RAAi in maximum tolerated doses. All patients were prescribed wit dapagliflozin 10 mg daily. We determine the changes from baseline of urinary protein/creatine (Up/cr) and glomerular filtration rate (based on epiGFR formula). Results Eight AS patients were included in this study. All were male patients. One patient has XLAS and the other 7 patients have ADAS. No patient was diabetic, and all were under RAAi in maximum tolerated doses. We determine de Up/cr and epiGFR at baseline and median time of 213.5 days (IQR 208.3-259) after SGLT2i initiation. At baseline, the median of Up/cr was 1.4 (IQR 0.8-2.1) and after SGLT2i Up/cr was 1.5 (0.8-2.6), p = 0.727. Up/cr, after SGLT2i treatment, reduced in 3 patients and worsened in 5. Median epiGFR at baseline was 80.3 ml/min (IQR 40.9-109.5) and after SGLT2i initiation was 74.7 ml/min (40.4-112.0), p = 0.727. Conclusion In this study, we did not observe an improvement in Up/cr of AS patients with SGLT2i treatment. A slight decrease in GFR was observed that may be due to the well know hemodynamic effects of SGLT2i. The small cohort and short time of the study are factors that can interfere in these results and should not discourage the treatment of AS patients with SGLT2i.

#226 Outcome of intermittent hemodialysis vs. continuous kidney replacement therapy for acute kidney injury: observational prospective multi-center study

Abstract Background and Aims Continuous hemodialysis in hemodynamically stable acute kidney injury (AKI) patients may impact outcome differently compared to intermittent hemodialysis, although this issue is controversial. We look at differences in AKI outcomes between patients treated with intermittent hemodialysis (IHD) and patients treated with continuous kidney replacement therapy (CKRT) modalities in in Kuwait. Method Clinically and hemodynamically stable adult inpatients with native kidneys (i.e., did not need inotropic support or mechanical ventilation) who received IHD or CKRT for AKI, in seven public hospitals in Kuwait between 1/January to 31/December 2021 were recruited. CKRT was selected due to lack of access to water treatment in patients wards in some of the participating hospitals. Demographics, comorbidities, dialytic and non-dialytic management data, and 30-day kidney and patient outcome data for, were prospectively collected and analyzed. Results Total number of AKI patients not on inotropic support and not mechanically ventilated who received dialysis during study period was 229 (age: 59.9 years; males: 60.3%; baseline eGFR: 56 ml/min). IHD (group 1) was performed in 27.1% of the cohort whereas CKRT (group 2) was performed in 72.9%. There was no statistically significant difference between the two groups in age (58.4 for IHD and 59.9 for CKRT, p=0.6), baseline eGFR (55 ml/min for IHD and 56.4 for CKRT, p=0.8), sex ratio, incidence of diabetes, hypertension or cardiovascular disease, or cause of AKI. However, renin angiotensin aldosterone system inhibitors (RAASi) were precipitating factors for AKI more significantly in the IHD group (25.8% vs. 6% for CKRT, P ≤ 0.001). Intensive care unit (ICU) contributed 21% of cases (14.5% for IHD and 23.4% for CKRT, insignificant p value of 0.1). Also, there was no statistically significant difference in receiving intravenous fluids between the two groups (71% for IHD vs. 71.5% for CKRT, p=0.8), however, more patients in the IHD group received diuretics (62.9% vs 43.1% for CKRT, p=0.008). Dialysis vascular access was right internal jugular vein in 59% (75.8% FOR IHD vs. 52.7% for CKRT) followed by femoral vein in 35% of cases (19.4%). Extracorporeal membrane oxygenation (ECMO) was used in only two cases in the CKRT group. Of the total cohort, 21.8% died, with no difference between the two groups (16.1% for IHD vs 24% for CKRT, p=0.2). Partial recovery was higher in IHD group (30.8% vs.17.3%, p=0.046) and complete recovery higher in CKRT group 33.1% vs 13.5%, p=0.009). eGFR at 30 days was 53.2 ml/min with no statistically significant difference between the two groups (44.6 for IHD vs 56.1 for CKRT, p=0.15). Conclusion The IHD group and the CKRT group were statistically similar in basic characteristics and received similar lines of management, except for the diuretics. At 30 days, they had similar death rates but CKRT group had higher rates of complete recovery than the IHD group. This is in line with published literature that suggest CKRT may not improve mortality but may improve kidney recovery.

#1452 Halting the progression of chronic kidney disease; an audit of the use of renin-angiotensin-aldosterone blockers and SGLT-2 inhibitors

Abstract Background and Aims Sodium-glucose cotransporters-2 inhibitors (SGLT2i) were initially developed for the treatment of type 2 diabetes. Multiple studies have demonstrated the renoprotective effect of SGLT2i, with the capacity to slow diabetic kidney disease and non-diabetic proteinuric chronic kidney disease progression. More recently, the EMPA-KIDNEY trial demonstrated a benefit in patients with chronic kidney disease with a wider range of albuminuria and glomerular filtration rate. We aim to identify the proportion of patients on renin-angiotensin aldosterone system blockade (RAASb) such as angiotensin converting enzyme inhibitor (ACEi), and angiotensin II receptor blocker (ARB), and sodium-glucose transporter-2 inhibitor (SGLT2i) in our Nephrology outpatients clinic. We also aim to encourage awareness and prescribing of RAASb and SGLT2i in eligible patients with CKD. Method A prospective audit was performed in Galway University Hospital (GUH) from September 2023 to October 2023. The audit questionnaire was completed by doctors reviewing patients in OPD. The use of ACEi/ARB/SGLT2i was recorded during the consultation. Results 165 patients were included in the audit with a mean (±SD) age of 62.1 ± 18.6 years. The 3 most common primary renal diagnoses were diabetic kidney disease; 20/165 (12.1%), hypertensive renal disease; 18/165 (10.9%) and IgA nephropathy; 15/165 (9.1%). The mean estimated glomerular filtration rate (eGFR) was 46.8 ± 24.5 ml/min/1.73 m². At baseline, 94/165 (57%) were already on RAASb, none on dual RAASb agents. 20/165 (12.1%) were already on SGLT2i, amongst these, 15/20 (75%) were also on RAASb at the time of the OPD consultation. 13/165 (7.9%) patients were maximised on RAASb and 4/165 (2.4%) commenced an SGLT2i at the clinic visit. Guideline directed medical therapy according to the EMPA-Kidney and UK Kidney Association Clinical Practice Guidelines would suggest missed opportunity on therapeutic optimisation with RAASb and SGLT2i in 66/83 (79.5%) patients; 26/66 (39.4%) were neither on RAASb or SGLT2i, 34/66 (51.5%) were on RAASb but not on SGLT2i, 3/66 (4.5%) were on SGLT2i but not on RAASb, and 3/66 (4.5%) were on sub-maximal RAASb with an SGLT2i. Conclusion There is new evidence to support the use of SGLT2i, in those with chronic kidney disease with a wide range of albuminuria. SGLT2i use is underutilised in our clinic. Ideally, these patients should be initiated on an SGLT2i after being established on a RAASb early in their diagnosis to ensure the optimal renoprotective effects of SGLT2i.

Hyperkalemia in chronic kidney disease patients with and without heart failure: an Italian economic modelling study

BackgroundHyperkalemia (HK) is frequently present in chronic kidney disease (CKD). Risk factors for HK among CKD patients include comorbidities and renin–angiotensin–aldosterone system inhibitor (RAASi) treatment. Current standard of care (SoC) often necessitates RAASi down-titration or discontinuation, resulting in poorer cardiorenal outcomes, hospitalization and mortality. This study evaluates the cost-effectiveness of patiromer for HK in CKD patients with and without heart failure (HF) in an Italian setting.MethodsA lifetime Markov cohort model was developed based on OPAL-HK to assess the health economic impact of patiromer therapy in comparison to SoC after accounting for the effects of HK and RAASi use on clinical events. Outcomes included accumulated clinical events, number needed to treat (NNT) and the incremental cost-effectiveness ratio (ICER). Subgroup analysis was conducted in CKD patients with and without HF.ResultsPatiromer was associated with an incremental discounted cost of €4,660 and 0.194 quality adjusted life years (QALYs), yielding an ICER of €24,004. Per 1000 patients, patiromer treatment prevented 275 moderate/severe HK events, 54 major adverse cardiovascular event, 246 RAASi discontinuation and 213 RAASi up-titration/restart. Subgroup analysis showed patiromer was more effective in preventing clinical events in CKD patients with HF compared to those without; QALY gains were greater in CKD patients without HF versus those with HF (0.267 versus 0.092, respectively). Scenario analysis and sensitivity analysis results support base-case conclusions.ConclusionPatiromer is associated with QALY gains in CKD patients with and without HF compared to SoC in Italy. Patiromer prevented HK events, enabled RAASi therapy maintenance and reduced cardiovascular event risk.

Beyond blood pressure, fluid and electrolyte homeostasis - Role of the renin angiotensin aldosterone system in the interplay between metabolic diseases and breast cancer.

The classical renin angiotensin aldosterone system (RAAS), as well as the recently described counter-regulatory or non-canonical RAAS have been well characterized for their role in cardiovascular homeostasis. Moreover, extensive research has been conducted over the past decades on both paracrine and the endocrine roles of local RAAS in various metabolic regulations and in chronic diseases. Clinical evidence from patients on RAAS blockers as well as pre-clinical studies using rodent models of genetic manipulations of RAAS genes documented that this system may play important roles in the interplay between metabolic diseases and cancer, namely breast cancer. Some of these studies suggest potential therapeutic applications and repurposing of RAAS inhibitors for these diseases. In this review, we discuss the mechanisms by which RAAS is involved in the pathogenesis of metabolic diseases such as obesity and type-2 diabetes as well as the role of this system in the initiation, expansion and/or progression of breast cancer, especially in the context of metabolic diseases.

The role of donor hypertension and angiotensin II in the occurrence of early pancreas allograft thrombosis

BackgroundAbout 10–20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis.MethodsWe conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers.ResultsPancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers.ConclusionDonor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

Benefit of Renin Angiotensin Aldosterone Blockade in Kidney Transplant Recipients: Is the Verdict in or Still to Be Answered?

Benefit of Renin Angiotensin Aldosterone Blockade in Kidney Transplant Recipients: Is the Verdict in or Still to Be Answered?

WEARABLE CARDIOVERTER–DEFIBRILLATORS IN CLINICAL PRACTICE IMPLEMENTATION OF THE ANMCO POSITION PAPER FOR APPROPRIATE USE OF THE WEARABLE CARDIOVERTER DEFIBRILLATOR

Abstract Introduction Wearable cardioverter–defibrillators (WCD) have emerged as a valuable tool in the management of patients at risk for life–threatening arrhythmias. These devices offer a non–invasive and temporary solution, providing continuous monitoring and the potential for prompt defibrillation when needed. In this study, we explore the indications for WCD and evaluate arrhythmic events through comprehensive monitoring. Methods From November 2022 to December 2023, we conducted an outpatient follow–up of 18 patients receiving WCD. Regular check–ups and comprehensive echocardiography were performed to optimize therapy based on specific indications for each patient. Results The average age of the patients was 59.3±17.4 years, with 79% being male. Among the cohort, 58% had hypertension, and a similar percentage comprised smokers and individuals with dyslipidemia, while 32% were diabetic. The indications for receiving WCD were: de novo diagnosis of dilated cardiomyopathy with reduced ejection fraction in 9 (50%) patients, recent acute coronary syndrome and ejection fraction < 35% in 5 (28%), cardiac electronic device infections in 3 (17%) patients and myocarditis with electrical instability in 1 (5%) patient. Patients were in optimal medical therapy (OMT) tailored to their specific comorbidities, with 84% on renin–angiotensin–aldosterone system inhibitors, 95% on beta–blockers, 53% on mineralocorticoid receptor antagonists, 53% on sodium–glucose cotransporter–2 inhibitors, and 37% on antiarrhythmics. The average follow–up was 64±45 days according to specific etiology, with a daily wearing time of 22.9±1.1 hours. No device interventions were recorded. At the end of the follow–up period, 6 (33%) patients still required implantable cardioverter–defibrillator (ICD). Among these, 4 patients (22%) underwent to ICD implantation, 3 for secondary prevention, and 1 for primary prevention, while notably, 2 (11%) patients, declined the procedure. Conclusions The use of wearable cardioverter–defibrillators in the outpatient setting for patients at risk of life–threatening arrhythmias allowed to optimize therapy and restrict the indications for ICD, in our cohort up to 67%, with a good safety profile due to the low incidence of device interventions.

SERUM OSMOLARITY ON ADMISSION ACUTE HEART FAILURE AND SHORT–TERM MORTALITY

Abstract Background Serum osmolality has been reported to be infuenced by well–known prognostic factors such as arginine vasopressin, the renin–angiotensin–aldosterone system, and natriuretic peptides, which suggest that osmolality itself could be also associated with the prognosis of heart failure. However, previous studies in acute heart failure (AHF) reported conflicting results on the prognostic role of serum osmolality. Methods We conducted a retrospective cohort study in subjects hospitalized with AHF between 2022 and 2023 in order to determine the association between serum osmolality at admission and 90–days mortality using Cox proportional hazard and Kaplen–Meier models. Results The study group consisted of 166 AHF patients (male 51%), mean age of 80 ± 9 years) with serum osmolarity 282± 11 mOsm/L and 90–days mortality equal to 23%. At univariate analysis, osmolality was significantly associated with mortality (HR 0.96, 95% CI 0.94–0.96). The optimal cut–off values for mortality was <280 mOsm/L (AUC 0.61; VPV 33 VPN 84). After adjustment for sex, age, BNP, renal and left ventricular functions, osmolality remained significantly and independently associated with mortality (HR 0.97, 95% CI 0.95–0.99). Conclusions Lower levels of serum osmolality on admission were related to short–term mortality in patients with AHF, suggesting that this could help stratify the risk of early mortality.

UNRAVELING GENDER DISPARITIES AND PROGNOSTIC INSIGHTS IN MODERATE AORTIC STENOSIS: A RETROSPECTIVE STUDY

Abstract Aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries, associated with reduced survival if severe AS remains untreated. Recent reports note unfavorable outcomes in moderate AS (mAS) patients, challenging optimal intervention timing. Variations in pathophysiology linked to sex differences, involving sex hormones, activation of the renin–angiotensin–aldosterone system, and dysregulation in collagen synthesis, have been observed. Yet, limited data exists on sex–specific differences in mAS outcomes. This single–center, retrospective study included 150 patients (median age 79±13 years, female sex 48%) diagnosed with mAS who underwent comprehensive echocardiography in IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico of Milan from July 2022 to October 2023. Clinical data, encompassing demographics details and therapy, were obtained via record reviews and phone interviews. Death verification relied on the ‘Sistema Informativo Socio–Sanitario Regione Lombardia’ database. Echocardiographic records were digitally stored and post–processed by four independent investigators using Medimatic ComPACS workstation. Men were significantly younger than women (75±10 vs 79±9.7 years, p= 0.016). They exhibited lower left ventricular (LV) ejection fraction, larger LV end–systolic volume and stroke volume compared to women (54±7 vs 59±10%; p=0.028. 55±36 vs 31±13 ml; p<0.001. 83±18 vs 75±18 ml; p=0.030). Men had significantly smaller aortic valve (AV) area index to body surface area (BSA) (0.6±0.09 vs 0.7±0.1 cmq/mq; p<0.001) and lower doppler velocity index (0.32±0.07 vs 0.38±0.11; p<0.001) than women. Coronary artery disease and smoking were more frequent in men (53.3 vs 46.7%; p=0,002. 52.6 vs 47.4%; p<0.001). In survival analysis, 15% of women and 30.8% of men experienced events, with male gender independently associated with the composite outcome (all–cause mortality and AV replacement) over a mean follow–up time of 200 ± 133 days, showing a median survival of 244±16 vs 255±15 days for females (p–value=0.025). In multivariable analysis including relevant clinical variables (hemoglobin and AV index to BSA), male sex remained independently associated with the composite outcome (hazard ratio 2,01; CI 1.0–4.17; p=0.05). Women diagnosed with mAS exhibited a lower incidence of AV replacement and all–cause mortality. These findings may suggest the existence of different clinical and echocardiographic phenotypes among patients with AS.

Selective venous sampling for secondary hypertension.

Selective venous sampling (SVS), an invasive radiographic procedure that depends on contrast media, holds a unique role in diagnosing and guiding the treatment of certain types of secondary hypertension, particularly in patients who may be candidates for curative surgery. The adrenal venous sampling (AVS), in particular, is established as the gold standard for localizing and subtyping primary aldosteronism (PA). Throughout decades of clinical practice, AVS could be applied not only to PA but also to other endocrine diseases, such as adrenal Cushing syndrome (ACS) and Pheochromocytomas (PCCs). Notably, the application of AVS in ACS and PCCs remains less recognized compared to PA, with the low success rate of catheterization, the controversy of results interpretation, and the absence of a standardized protocol. Additionally, the AVS procedure necessitates enhancements to boost its success rate, with several helpful but imperfect methods emerging, yet continued exploration remains essential. We also observed renal venous sampling (RVS), an operation akin to AVS in principle, serves as an effective means of diagnosing renin-dependent hypertension, aiding in the identification of precise sources of renin excess and helping the selection of surgical candidates with renin angiotensin aldosterone system (RAAS) abnormal activation. Nonetheless, further basic and clinical research is needed. Selective venous sampling (SVS) can be used in identifying cases of secondary hypertension that are curable by surgical intervention. Adrenal venous sampling (AVS) and aldosterone measurement for classificatory diagnosis of primary aldosteronism (PA) are established worldwide. While its primary application is for PA, AVS also holds the potential for diagnosing other endocrine disorders, including adrenal Cushing's syndrome (ACS) and pheochromocytomas (PCCs) through the measurements of cortisol and catecholamine respectively. In addition, renal venous sampling and renin measurement can help to diagnose renovascular hypertension and reninoma.

Mineralocorticoid receptor antagonists and reno-protection: What's the evidence & where do they fit? A guide for non-specialists.

The role of aldosterone has yet to be well appreciated in chronic kidney disease (CKD). Two variables define CKD: an estimated glomerular filtration rate of <60 ml/min/1.73 m2 and a spot urine albumin-creatinine ratio of >30 mg/g. Both are needed for an accurate diagnosis. The presence of CKD at this level is associated with an elevated risk of cardiovascular death and a greater risk of CKD progression to kidney failure and subsequent dialysis. This paper presents an overview of aldosterone's importance in CKD and its contribution to the inflammatory processes involved in CKD development. Data on outcomes, both surrogate and hard, related to outcomes on CKD progression will also be discussed in the context of mineralocorticoid blockade. Based on recent epidemiological data as well as data examining markers of diabetic kidney disease progression, it is clear that use of both renin-angiotensin system inhibitors and aldosterone receptor antagonists have a significant role in altering the natural history of kidney disease progression itself, as well as reducing the risk of cardiovascular events that generally accompany long-standing kidney disease. This paper will discuss these issues and the management of consequent hyperkalaemia when both steroidal and non-steroidal mineralocorticoid receptor antagonists are used in detail.

Medical treatment of heart failure with renin–angiotensin–aldosterone system inhibitors and beta-blockers in aortic stenosis: association with long-term outcome after aortic valve replacement

Abstract Aims There is a lack of robust data on the optimal medical treatment of heart failure in patients with severe aortic stenosis, with no randomized controlled trials guiding treatment. The study aimed to study the association between exposure to renin–angiotensin–aldosterone system (RAS) inhibitors or beta-blockers and outcome after aortic valve replacement in patients with aortic stenosis and heart failure. Methods and results The study included all patients with heart failure undergoing aortic valve replacement for aortic stenosis in Sweden between 2008 and 2016 (n = 4668 patients). Exposure to treatment was assessed by a continuous tracking of drug dispensations, and outcome events were all-cause mortality and hospitalization for heart failure collected from national patient registries. After adjustment for age, sex, atrial fibrillation, hypertension, diabetes mellitus, and prior myocardial infarction, Cox regression analysis showed that RAS inhibition was associated with a lower risk of all-cause mortality in patients with reduced left ventricular ejection fraction (LV-EF) [hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51–0.65] and preserved LV-EF (HR 0.69, 95% CI 0.56–0.85). Beta-blockade was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.81, 95% CI 0.71–0.92), but not in preserved LV-EF (HR 0.87, 95% CI 0.69–1.10). There was no association between RAS inhibition or beta-blockade and the risk of hospitalization for heart failure. Conclusion The RAS inhibition was associated with a lower all-cause mortality after valve replacement in patients with both reduced and preserved LV-EF. Beta-blockade was associated with lower all-cause mortality only in patients with reduced LV-EF.

Multidisciplinary proactive e-consults to improve guideline-directed medical therapies for patients with diabetes and chronic kidney disease: an implementation study

IntroductionWe hypothesized that multidisciplinary, proactive electronic consultation (MPE) could overcome barriers to prescribing guideline-directed medical therapies (GDMTs) for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).Research design...

COVID-19 and Hypertensive Disorders of Pregnancy: Is the Placenta the Problem? [ID 2683611

INTRODUCTION: The objective of this study is to evaluate the association between COVID-19 infection in pregnancy and placental pathology in order to assess the mechanism of its association with hypertensive disorders of pregnancy (HDP). METHODS: This was a retrospective cohort study that compared placentas of patients who tested positive for COVID-19 during their pregnancy (n=70) to placentas of patients who tested negative for COVID-19 (controls, n=210). Patient demographics, comorbid conditions, and pregnancy complications were obtained from the electronic medical record. RESULTS: Compared with pregnancies negative for COVID-19 infection, maternal COVID-19 infection was not associated with increased incidence of placental pathology including acute funisitis, acute chorioamnionitis, chronic villitis, chorionic pseudocysts, decidual necrosis, Tenney Parker changes, intervillous hemorrhage, infarcts, villous calcifications, meconium-stained amniotic fluid, inflammatory changes, or vascular VTE changes. Based on the logistic regression analysis, after controlling for other variables in the model, the risk of developing HDP was 72.4% higher in patients who tested positive for COVID-19 versus those who did not (odds ratio 1.72; 95% CI [1.09, 2.73]; P=.02). CONCLUSION: Patients who test positive for COVID-19 during pregnancy have an increased risk of HDP. However, there is no association between COVID-19 infection in pregnancy and pathologic findings on placental histology. This suggests that COVID-19 does not exert its effects of increasing the risk of HDP via placental infection or inflammation. Rather, COVID-19 may contribute to the pathogenesis of HDP through cytokine storm, dysregulation of the renin–angiotensin–aldosterone system, or systemic hyperinflammatory response.

Case Report of a Large Endometrioma Precipitating a Hypertensive Emergency [ID 2683395

INTRODUCTION: This is a rare case of a 25-cm endometrioma in a woman who presented in a hypertensive emergency. The hypertension was believed to be secondary to the mass effect of the endometrioma on renal vasculature. METHODS: A 20-year-old female presented to the ED with diffuse abdominal pain, severe hypertension (190/121), and acute kidney injury (AKI) (Cr 2.4, GFR 38). At presentation, management of hypertension required intravenous hydralazine and adequate pain control. The workup included an abdominal CT that revealed a large 25×18×12-cm cystic mass. The mass was suspected to have a significant mass-effect on adjacent structures that caused bilateral hydroureteronephrosis secondary to distal ureteral compression. Management of this case began with the placement of bilateral nephrostomy tubes to improve renal function. The pelvic mass was removed with a minimally invasive robotic approach. The patient had an uneventful postoperative course with normalization of blood pressure and resolution of the AKI. Pathology confirmed the diagnosis of endometriosis. Prior to the removal of nephrostomy tubes, a nephrostogram was performed, which demonstrated appropriate drainage bilaterally. At 1 year follow-up, the patient was asymptomatic and was able to conceive. This case report was IRB-exempt. CONCLUSION: A multidisciplinary approach to the management of endometriosis is often warranted as it may affect organs outside of the reproductive system. In this case, the etiology of hypertension is believed to be due to mass effect of the cyst on the renal arteries. Low renal perfusion activates the renin–angiotensin–aldosterone system, releasing Angiotensin II and aldosterone, causing systemic vasoconstriction and secondary hypertension. In this case, a minimally invasive approach to remove the mass and ureterolysis resulted in the resolution of the pelvic pain, AKI, and normalization of blood pressure.

IN ARTERIAL HYPERTENSION THE RIGHT VENTRICLE IS NO LONGER THE “FORGOTTEN CAVITY”

Objective: The right ventricle showed late interest in the assessment and stratification of the severity of arterial hypertension. The complex systemic reaction in the context of arterial hypertension, represented in particular by the activation of the renin angiotensin aldosterone system and the increase in sympathetic activity would suggest an early impairment of diastolic and later systolic function also of the right ventricle. Echocardiography is the most accessible way to evaluate the right ventricle in medical practice. Purpose of the study: to evaluate the precocity and the type of right ventricular function impairment in recently diagnosed hypertensive patients. Design and method: The patients were included after following the recommendations for the diagnosis of arterial hypertension according to the guide published by ESH in 2023. Personal biological data and parameters, cardiovascular risk factors, blood pressure values were recorded. Patients with other comorbidities, with secondary hypertension were excluded.Patients on antihypertensive treatment were also excluded. We investigated echocardiographically by analyzing 2D diastolic parameters, Doppler spectral and mitral and tricuspid tissue parameters as well as the global longitudinal strain of both ventricles. We studied right ventricle global longitudinal strain (RVGLS), septal wall longitudinal strain (RVSWLS), right ventricle lateral wall longitudinal strain (RVLWLS). Results: we studied a group of 61 patients who presented with essential hypertension, recently diagnosed, with an average age of 68.1 +- 6.3 years and who were analyzed according to grade, gender, risk factors. The (RVGLS) was analyzed separately and comparatively for the lateral and septal wall and the values were RVGLS =19%+- 3.2%. RVSWLS=-13.1% +-2.9% and RVFWLS=-22.6%+- 3.4%. The filling ratio of the right ventricle E/e’ was 14. Conclusions: the diastolic function of the right ventricle is affected in recently diagnosed hypertensive patients in relation to the degree of hypertension, myocardial mass and the filling ratio of the left ventricle. Slightly increased values of RVLWGLS could be interpreted as a consequence of sympathetic activation

Patiromer to Reduce Albuminuria through Increased Renin Angiotensin Aldosterone System Inhibition in Patients With CKD-A Feasibility Trial

IntroductionWe tested the feasibility of adding a potassium binder to enable increased RAASi and reduce albuminuria in patients with CKD. In a controlled trial design, a potassium binder was introduced exclusively in patients developing hyperkalaemia following intensified RAASi, thereby mirroring clinical decision-making. MethodsWe planned to include 140 patients aged 18-80 with eGFR 25-60 mL/min/1,73m2, albuminuria, and a history of hyperkalaemia to an open-label, randomized trial comparing treatment with or without patiromer alongside maximally tolerated RAASi. Patients were randomized only if developing a documented P-potassium >5.5 mmol/L during run-in with intensified RAASi (losartan/spironolactone). The primary endpoint was change in urine albumin creatinine ratio. ResultsScreening among 800,000 individuals with available laboratory results yielded just 317 candidates meeting major selection criteria during 18⅔ months, with 75 ultimately included. Among them, only 23 developed P-potassium >5.5 mmol/L, qualifying for randomization. Consequently, only 20 participants completed the study, falling short of the planned 98, precluding a significant effect on the primary outcome. Inclusion and randomization challenges stemmed from a limited pool of eligible patients for intensified RAASi at risk of hyperkalaemia, along with a lower-than-expected incidence of hyperkalaemia during run-in. ConclusionDespite extensive screening efforts, few eligible patients were identified, and fewer developed hyperkalaemia during run-in. Hence, a trial design limited to CKD patients at high hyperkalaemia risk and including a run-in phase appears unlikely to provide evidence for a potential renal benefit from additional use of potassium binders.

Effects of potassium supplementation and deficiency on the progression of salt-sensitive hypertension

While the physiological effects of sodium on blood pressure are well established, many of the effects of potassium remain unclear. Prior work found that increased potassium intake decreases blood pressure and risk of cardiovascular disease, improves vasodilation, has reno-protective effects, and can stimulate natriuresis. In this study, we examined how different sodium/potassium ratios affect the development of salt-sensitive hypertension, specifically examining changes in the kidney and the renin angiotensin aldosterone system (RAAS). We hypothesized that blood pressure would directly correlate to the Na+/K+ ratio and that there would be compensatory changes in RAAS and in expression of renal potassium channels, particularly inwardly rectifying potassium (Kir) channels. At 9 weeks of age, male and female Dahl SS rats were placed on a high salt (4% NaCl) diet for 5 weeks with normal potassium (NK, 0.36% K+), high potassium (HK, 1.41% K+), or potassium depleted (DK, &lt;0.0001% K+) diet. After 5 weeks of dietary intervention, DK animals were hypokalemic, and HK animals had significantly increased plasma potassium. Potassium supplementation attenuated the development of salt-sensitive hypertension in male rats fed the HK diet compared to NK; the DK group did not develop hypertension. Potassium supplementation did not attenuate blood pressure in female rats, who also had a higher mortality rate on the DK diet. Heart rates were unchanged in both male and female HK groups but were significantly lower in the DK groups of both sexes. After 5 weeks of diet, the total body weights of DK rats were significantly lower. The 2 kidney/total body weight ratios were not different between the HK and NK groups, but the kidneys of the DK group were significantly larger, likely due to their smaller body weights. Medullary protein casts in DK rats of both sexes were decreased but no renoprotective effects were observed in the HK group. Western blot analysis of renal potassium channels demonstrated no changes in the expression of ROMK, significantly increased Kir5.1 in DK males and females, and a significant increase in Kir4.1 and the alpha-subunit of the Na+/K+-ATPase in DK males. We analyzed RAAS metabolites from plasma samples collected at the endpoint: Ang I (1-10), Ang IV (3-8), and Ang (1-5) were significantly decreased in DK males and females, Ang II (1-8) and Ang III (2-8) were significantly reduced in DK males, and aldosterone was significantly increased in HK males and females. These results provide a comprehensive assessment of how various potassium diets affect the development of salt-sensitive hypertension in both males and females, which will provide a solid foundation for future mechanistic studies. R01DK129227, I01 BX004024, R35HL135749. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.