Hyperkalemia Events Research Articles

The Utility of Monitoring Potassium in Transgender, Gender Diverse, and Nonbinary Individuals on Spironolactone.

ContextCurrent Endocrine Society guidelines recommend that transgender women taking spironolactone have their potassium levels checked every 3 months for the first year after initiating therapy and annually thereafter to monitor for hyperkalemia.ObjectiveThe goal of this study was to assess the need for such frequent potassium monitoring and to investigate whether age plays a role in potassium abnormalities in transgender, gender diverse, and nonbinary (TGDNB) individuals taking spironolactone.MethodsUsing EPIC-Clarity, a retrospective study of healthy, adult individuals with gender-identity disorder listed in their problem list and taking spironolactone was performed. We analyzed the incidence of hyperkalemia in this population. Data from June 2006 through November 2021 were obtained. Exclusion criteria included hypertension, renal failure, diabetes mellitus, heart failure, and medications that affect the renin–angiotensin–aldosterone system.Results318 healthy TGDNB individuals met our inclusion criteria. We identified 8/318 (2.5%) individuals with hyperkalemia on spironolactone. There was a significant difference in incidence of hyperkalemia events in those >45 years old and those ≤45 years old (8.9% vs 1.5%, P = .016).ConclusionOur data suggest the incidence of hyperkalemia in our TGDNB population is low, particularly in those ≤45 years old; however, this risk increases with age. These findings suggest practice guidelines may need to be adjusted to minimize unnecessary testing in the population ≤45 years old who are not plagued by comorbidities that affect potassium handling.

Cost effectiveness of sodium zirconium cyclosilicate for the treatment of hyperkalaemia in patients with CKD in Norway and Sweden

BackgroundHyperkalaemia is common in patients with chronic kidney disease (CKD) and is associated with a range of adverse outcomes. Historically, options for management of chronic hyperkalaemia in the outpatient setting have been limited. Novel oral potassium binders provide a safe, effective therapy for maintenance of normokalaemia in patients with CKD, but despite being approved for reimbursement in many countries, prescription data indicate uptake has been slower than anticipated. This analysis aimed to demonstrate the value to patients and the healthcare system of the potassium binder sodium zirconium cyclosilicate (SZC) for treatment of hyperkalaemia in patients with CKD in Norway and Sweden.MethodsA published simulation model reflecting the natural history of CKD was adapted to the Norwegian and Swedish settings and used to predict long-term health economic outcomes of treating hyperkalaemia with SZC versus usual care.ResultsSZC was highly cost effective compared to usual care in Norway and Sweden, with incremental cost-effectiveness ratios of €14,838/QALY in Norway and €14,352/QALY in Sweden, over a lifetime horizon. The acquisition cost of SZC was largely offset by cost savings associated with reductions in hyperkalaemia events and hospitalisations; a modest overall increase in costs was predominantly attributable to costs associated with gains in life years compared with usual care. SZC remained cost effective in all scenarios examined.ConclusionsSZC was estimated to be cost effective for treating hyperkalaemia. Consequently, improving access to a clinically effective, safe and cost-effective therapy, such as SZC, may result in considerable benefits for CKD patients with hyperkalaemia.

Noninvasive Screening Tool for Hyperkalemia Using a Single-Lead Electrocardiogram and Deep Learning: Development and Usability Study.

BackgroundHyperkalemia monitoring is very important in patients with chronic kidney disease (CKD) in emergency medicine. Currently, blood testing is regarded as the standard way to diagnose hyperkalemia (ie, using serum potassium levels). Therefore, an alternative and noninvasive method is required for real-time monitoring of hyperkalemia in the emergency medicine department.ObjectiveThis study aimed to propose a novel method for noninvasive screening of hyperkalemia using a single-lead electrocardiogram (ECG) based on a deep learning model.MethodsFor this study, 2958 patients with hyperkalemia events from July 2009 to June 2019 were enrolled at 1 regional emergency center, of which 1790 were diagnosed with chronic renal failure before hyperkalemic events. Patients who did not have biochemical electrolyte tests corresponding to the original 12-lead ECG signal were excluded. We used data from 855 patients (555 patients with CKD, and 300 patients without CKD). The 12-lead ECG signal was collected at the time of the hyperkalemic event, prior to the event, and after the event for each patient. All 12-lead ECG signals were matched with an electrolyte test within 2 hours of each ECG to form a data set. We then analyzed the ECG signals with a duration of 2 seconds and a segment composed of 1400 samples. The data set was randomly divided into the training set, validation set, and test set according to the ratio of 6:2:2 percent. The proposed noninvasive screening tool used a deep learning model that can express the complex and cyclic rhythm of cardiac activity. The deep learning model consists of convolutional and pooling layers for noninvasive screening of the serum potassium level from an ECG signal. To extract an optimal single-lead ECG, we evaluated the performances of the proposed deep learning model for each lead including lead I, II, and V1-V6.ResultsThe proposed noninvasive screening tool using a single-lead ECG shows high performances with F1 scores of 100%, 96%, and 95% for the training set, validation set, and test set, respectively. The lead II signal was shown to have the highest performance among the ECG leads.ConclusionsWe developed a novel method for noninvasive screening of hyperkalemia using a single-lead ECG signal, and it can be used as a helpful tool in emergency medicine.

Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Hyperkalemia in People With Type 2 Diabetes: A Meta-Analysis of Individual Participant Data From Randomized, Controlled Trials.

Hyperkalemia increases risk of cardiac arrhythmias and death and limits the use of renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists, which improve clinical outcomes in people with chronic kidney disease or systolic heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of cardiorenal events in people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease. However, their effect on hyperkalemia has not been systematically evaluated. A meta-analysis was conducted using individual participant data from randomized, double-blind, placebo-controlled clinical outcome trials with SGLT2 inhibitors in people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease in whom serum potassium levels were routinely measured. The primary outcome was time to serious hyperkalemia, defined as central laboratory-determined serum potassium ≥6.0 mmol/L, with other outcomes including investigator-reported hyperkalemia events and hypokalemia (serum potassium ≤3.5 mmol/L). Cox regression analyses were performed to estimate treatment effects from each trial with hazards ratios and corresponding 95% CIs pooled with random-effects models to obtain summary treatment effects, overall and across key subgroups. Results from 6 trials were included comprising 49 875 participants assessing 4 SGLT2 inhibitors. Of these, 1754 participants developed serious hyperkalemia, and an additional 1119 investigator-reported hyperkalemia events were recorded. SGLT2 inhibitors reduced the risk of serious hyperkalemia (hazard ratio, 0.84 [95% CI, 0.76-0.93]), an effect consistent across studies (Pheterogeneity=0.71). The incidence of investigator-reported hyperkalemia was also lower with SGLT2 inhibitors (hazard ratio, 0.80 [95% CI, 0.68-0.93]; Pheterogeneity=0.21). Reductions in serious hyperkalemia were observed across a range of subgroups, including baseline kidney function, history of heart failure, and use of renin-angiotensin-aldosterone system inhibitor, diuretic, and mineralocorticoid receptor antagonist. SGLT2 inhibitors did not increase the risk of hypokalemia (hazard ratio, 1.04 [95% CI, 0.94-1.15]; Pheterogeneity=0.42). SGLT2 inhibitors reduce the risk of serious hyperkalemia in people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease without increasing the risk of hypokalemia.

MO487: Rates of Hyperkal a EMIA and Management Patterns in a Tertiary Outpatient Renal Clinic

Abstract BACKGROUND AND AIMS The optimal ambulatory management of hyperkalaemia (HK) in patients with chronic kidney disease (CKD) is still an important unmet challenge. Common strategies include dose reduction or discontinuation of nephroprotective medications (e.g. renin-angiotensin-aldosterone system inhibitors [RAASi]), dietary restriction of potassium (K), loop diuretics, bicarbonate and sodium polystyrene sulfonate; all the above interventions are characterized by specific pitfalls and limitations. However, new potassium binders are available that might improve the management of chronic hyperkalaemia. In the light of their widespread use, it will be important to increase our knowledge of the incidence, characteristics and current real-life management patterns of hyperkalaemia in CKD patients. METHOD We performed a retrospective analysis of patients followed at our tertiary outpatient renal clinic from 1 April 2016 to 31 December 2021. HK was defined as serum K > 5.0 mmol/L and stratified according to severity. eGFR was estimated with the CKD-EPI equation and stratified according to the KDIGO criteria. The time span between each episode of HK was assessed with Poisson regression models. A sample of 100 HK events was selected at random for manual chart review of the management strategies performed: Information was abstracted using a standardized form. RESULTS The final analysis included 1844 patients, contributing 4480 occasions. Baseline characteristics by hyperkalaemia status are reported in Table 1. Patients with HK were older, with lower eGFR and a higher prevalence of diabetes. At least one episode of HK was documented in 525 patients (28.5%) and among them, 166 patients (31.6%) had at least two HK episodes (on average, 1.55 episodes/patient). HK events were more frequent among patients with more advanced stages of CKD. The time span between episodes decreased significantly (Fig. 1): on average, each episode was 17% [95% confidence interval (95% CI), 3%–29%) closer to the subsequent (P = .016). Of the 100 HK episodes randomly reviewed, 79% received no intervention, whereas 21% triggered at least one intervention. The probability of intervention increased with increasing severity of HK: 8.6%, 35.9%, 50.0% and 100% for K-values 5.0–5.4, 5.5–5.9, 6.0–6.4 and ≥6.5 mmol/L, respectively. Most interventions included dose reduction or discontinuation of RAASi. One patient was sent to the emergency department for urgent examination and treatment (K 7.0 mmol/L). CONCLUSION Hyperkalaemia is a common and recurring problem for patients with renal impairment: It occurs in almost one-third of the overall population of this study, and many hyperkalaemic patients experience recurring events. As expected, the prevalence rates of hyperkalaemia increase with worsening CKD severity. Furthermore, the decreased time span between consecutive episodes highlights an accelerated recurrence pattern of hyperkalaemia despite interventions.

MO151: A Randomized Controlled Trial of Sodium Zirconium Cyclosilicate Versus Standard of Care for Hyperkalaemia in Chronic Kidney Disease: Phase 4 Continuity Study Design and Rationale

Abstract BACKGROUND AND AIMS Individuals hospitalized with hyperkalaemia (HK) and chronic kidney disease (CKD) are at very high risk of HK recurrence, which often requires hospital re-admission [1]. Recurrent HK events have a significant impact on healthcare resource utilization (HCRU) and costs [2]. Several approaches, such as reduction in dietary potassium (K+), reduction or discontinuation of diuretic and renin-angiotensin-aldosterone system inhibitor (RAASi), or oral K+ binders may be used to manage HK in the outpatient setting. Sodium zirconium cyclosilicate (SZC) is an orally administered, non-absorbed, highly selective K+ binder approved for the treatment of HK in adults. In phase 3 trials, after achieving normokalaemia (NK), individualized once-daily SZC therapy maintained normal range serum K+ levels for up to 1 year in adult outpatients [3]. However, it is unknown if SZC prevents HK recurrence compared with standard of care (SoC). Here, we present the rationale and design of the phase 4 CONTINUITY study (D9480C00023), which will compare the efficacy of continued SZC treatment, as part of the post-discharge medication regimen, with SoC, in maintaining NK and reducing HK-related hospital admissions and emergency department (ED) visits. METHOD CONTINUITY is a randomized controlled, open-label, parallel-group, multicentre study in participants with CKD treated for HK while in hospital, to be conducted in 30–50 study sites across four to seven European countries. The study will comprise both an in-hospital and an outpatient (post-discharge) phase (Figure). During the in-hospital phase, all participants will be treated with SZC to correct HK (SZC 10 g three times daily, up to 72 h) and maintain NK (SZC from 5 g every other day to 10 g once daily) as per local label for 2–14 days. At discharge, participants with NK established on an SZC maintenance dose will be randomised (1:1) to either SZC per local label (Arm A) or SoC per local practice (Arm B); participants intended to be discharged with a K+ binder will not be randomized and will be discontinued from the study. Following randomization, participants enter the outpatient phase and will be monitored for 180 days post-discharge via seven planned follow-up visits or phone calls, followed by a site visit at 7 days after end of treatment (Figure). Participants will be screened to yield 506 entering the in-hospital phase, resulting in 430 participants discharged and randomized (215 per arm) and 344 evaluable participants. Adults (≥18 years) with stage 3b–5 CKD or eGFR <45 mL/min/1.73 m2 at or within 3 months prior to study screening, who are admitted to hospital with a serum K+ of 5.5–6.5 mmol/L, will be eligible. The primary endpoint is the occurrence of NK (serum K+ 3.5–5.0 mmol/L) at 180 days post-discharge. Secondary and exploratory outcomes assessed within 180 days post-discharge include a composite endpoint of any HK-related hospital admission or ED visit, use of rescue therapy for HK and all-cause death, as well as RAASi treatment status and dose, and K+ level. Safety and tolerability will also be evaluated. CONCLUSION CONTINUITY is the first study to examine the efficacy of extended use of a novel K+ binder post-discharge compared with SoC, on the maintenance of NK and reduced HCRU among patients with HK, with CKD stage 3b–5. This study will address the importance of maintaining NK after discharge in routine clinical practice, and the impact of improved management of patients with CKD and HK.

The Impact of Hyperkalemia on Mortality and Healthcare Resource Utilization Among Patients With Chronic Kidney Disease: A Matched Cohort Study in China.

ObjectivesThis study aimed to estimate the impact of hyperkalemia on 1-year survival and all-cause healthcare resource utilization among patients with chronic kidney disease in China.MethodsAdult new-onset chronic kidney disease patients were identified between 2012 and 2016, among which the hyperkalemia and non-hyperkalemia cohorts were further selected and matched. Survival and all-cause healthcare resource utilization during a 12 month period were compared using Kaplan-Meier curves with log-rank test, Cox proportional hazard model, and Kaplan-Meier sample average method.ResultsAmong 1,003 pairs of patients (mean age 67.2 ± 14.3 years), the 1-year all-cause mortality was 5.39-times higher in the hyperkalemia cohort than the non-hyperkalemia cohort (hazard ratio = 5.39, P < 0.001). The mean costs and number of healthcare services among the hyperkalemia patients were significantly higher (P < 0.05) in each follow-up month. An annual increase cost of ¥38,479 was observed in the hyperkalemia cohort, largely due to the sharp increase in inpatient costs during the first month after hyperkalemia events (¥22,204 vs. 1,032, P < 0.001). Medication costs were the most important cost component for both cohorts [¥26,786 (45%) vs. ¥12,378(60%)]. However, hyperkalemia patients spent more on non-medication treatment [¥13,410(23%) vs. ¥2,335(11%)] including nursing, monitoring, etc. Hyperkalemia patients had more annual inpatient admissions (1.9 vs. 0.7) and length of stays (28.6 vs. 8.7), while the number of outpatient visits (36.8 vs. 36.4) were similar.ConclusionsIn Chinese chronic kidney disease patients, hyperkalemia is associated with substantially increased clinical and economic burdens that are driven by the short period following the hyperkalemia events, which strengthens calls for sufficient supervision and management of serum potassium.

RAAS Inhibitor Prescription and Hyperkalemia Event in Patients With Chronic Kidney Disease: A Single-Center Retrospective Study.

Hyperkalemia is common in patients treated with renin–angiotensin–aldosterone system inhibitors (RAASis), and it represents the main cause of the large gap reported between guideline recommendations and real-world practice in chronic kidney disease (CKD). We conducted a CKD-population-based restrospective study to determine the prevalence of patients with CKD treated with RAASis, incidence of hyperkalemia in patients with CKD treated with RAASis, and proportion of patients with RAASi medication change after experiencing incident hyperkalemia. Among 809 patients with CKD analyzed, 556 (68.7%) were treated with RAASis, and RAASi prescription was greater in stages 2–4 of CKD. Hyperkalemia occurred in 9.2% of RAASi-treated patients, and the adjusted rate of hyperkalemia among patients with stage 4–5 CKD was 3-fold higher compared with patients with eGFR > 60 ml/min/1.73 m2. RAASi treatment was discontinued in 55.3% of the patients after hyperkalemia event (74.2% discontinued therapy, 3.2% received a reduced dose, and 22.6% reduced the number of RAASi drugs). This study shows that the incidence of hyperkalemia is frequently observed in patients with CKD patients with RAASis, and that rates increase with deteriorating levels of kidney function from stages 1 to 3. RAASi medication change following an episode of hyperkalemia occurred in almost half of the patients after experiencing hyperkalemia.

Patiromer for the management of hyperkalaemia in patients receiving renin-angiotensin-aldosterone system inhibitors for heart failure: design and rationale of the DIAMOND trial.

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.

Analysis of risk factors for hyperkalemia in hemodialysis patients and establishment and verification of risk assessment model of hyperkalemia

Objective: To explore risk factors for hyperkalemia in hemodialysis (HD) patients, and establish and verify a risk assessment model of hyperkalemia in HD patients. Methods: The clinical data of HD patients who were admitted to the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University between April 2020 and January 2021 were retrospectively collected and divided into training dataset and validation dataset by using the conversion-random number generator. In the training dataset, multivariate logistic regression analysis was used to screen the risk factors for hyperkalemia in HD patients and the factors were scored to establish the risk assessment model. The validation dataset was substituted into the model and the receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to verify the effectiveness of the risk prediction model in predicting hyperkalemia. Results: A total of 502 HD patients were enrolled and further divided into training dataset (n=372) and validation dataset (n=130). There were 268 males and 234 females, with a mean age of (54±13) years. Multivariate logistic regression analysis showed that metabolic acidosis, high potassium diet, history of hyperkalemia, the change of electrocardiogram (ECG), disfunction of vascular access and time interval from last dialysis were risk factors for causing hyperkalemia in patients undergoing HD. Risk assessment model was established based on these risk factors. The AUC of the ROC curve was 0.799. Using 5 as the cut-off value, the sensitivity and specificity for predicting hyperkalemia events was 61.4% and 86.3%, respectively. Conclusion: The current study preliminarily established a risk assessment model for hyperkalemia in HD patients, which can help clinicians manage the potassium level of HD patients.

Efficacy and Safety of Finerenone in Patients with CKD and T2D by GLP-1RA Treatment

IntroductionFinerenone is a nonsteroidal mineralocorticoid receptor antagonist that significantly reduces risk of kidney and CV outcomes in patients with CKD and T2D. GLP-1RAs have also been shown to improve CV outcomes in patients with T2D. Mechanisms of action of finerenone and GLP-1RAs are largely independent but their combined effects are unknown. We report outcomes from the FIDELIO-DKD trial in patients by GLP-1RA treatment. MethodsFIDELIO-DKD (NCT02540993) randomized 5734 patients with T2D (UACR 30–5000mg/g; eGFR 25–<75mL/min/1.73 m2; treated with optimized RAS blockade) to finerenone or placebo. Primary outcome was time to kidney failure, sustained eGFR decline ≥40% from baseline, or renal death. Secondary outcomes included time to CV death, non-fatal MI, non-fatal stroke, or hospitalization for heart failure, and change in UACR from baseline to month 4. ResultsOf 5674 patients analyzed, 394 (6.9%) were treated with a GLP-1RA at baseline. There was no between-group interaction for primary kidney (HR 1.17, 95%CI 0.71–1.90 with GLP-1RA; HR 0.80, 95%CI 0.71–0.91 without GLP-1RA; P-interaction 0.15) or secondary CV outcomes (HR 1.02, 95%CI 0.60–1.74 with GLP-1RA; HR 0.85, 95%CI 0.73–0.98 without GLP-1RA; P-interaction 0.51). Reduction in UACR was independent of GLP-1RA use (ratio of LS-means 0.63, 95%CI 0.56–0.70 with GLP-1RA; 0.69, 95%CI 0.67–0.72 without GLP-1RA; P-interaction 0.20). Incidences of hyperkalemia events were similar in patients with and without GLP-1RA use. ConclusionEffects of finerenone on kidney and CV outcomes appear consistent irrespective of GLP-1RA use, with a potential additive benefit for UACR reduction.

Finerenone in Patients with CKD and T2D by SGLT-2i Treatment: An Analysis of the FIDELIO-DKD Study

IntroductionThe selective, nonsteroidal mineralocorticoid receptor antagonist finerenone was investigated in FIDELIO-DKD in patients with CKD and T2D (NCT02540993). Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are recommended for CKD in T2D to reduce risk of CKD progression. We report a predefined exploratory analysis of patients by SGLT-2i use. MethodsPatients (N=5674) with T2D, urine albumin-to-creatinine ratio (UACR) 30–5000 mg/g and estimated glomerular filtration rate (eGFR) 25–<75 mL/min/1.73 m2 receiving optimized RAS blockade were randomized to finerenone (10 mg daily increasing to 20 mg daily) or placebo. ResultsOf 5674 patients, 259 (4.6%) received SGLT-2i at baseline. Overall, finerenone significantly reduced the primary (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) vs placebo (p=0.001 and p=0.03, respectively) with no effect on A1C. Results were consistent irrespective of SGLT-2i use at baseline for the primary and key secondary CV outcomes (interaction p-value 0.21 and 0.46, respectively). Reduction in UACR with finerenone was seen without SGLT-2i use (ratio of LS-means 0.68, 0.65–0.71; p<0.0001) and on top of SGLT-2is at baseline (ratio of LS-means 0.75, 0.62–0.90; p=0.0024). Treatment-emergent hyperkalemia events were fewer with SGLT-2i vs no SGLT-2i (post hoc analysis). ConclusionThe benefits of finerenone on kidney and CV outcomes in patients with CKD and T2D appear consistent in the absence or presence of SGLT2i, with UACR improvement observed in patients already receiving SGLT-2i at baseline.

Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Sodium-Glucose Cotransporter-2 Inhibitor Therapy

IntroductionFIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) investigated the nonsteroidal, selective mineralocorticoid receptor (MR) antagonist finerenone in patients with CKD and type 2 diabetes (T2D). This analysis explores the impact of use of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on the treatment effect of finerenone.MethodsPatients (N = 5674) with T2D, urine albumin-to-creatinine ratio (UACR) of 30 to 5000 mg/g and estimated glomerular filtration rate (eGFR) of 25 to <75 ml/min per 1.73 m2 receiving optimized renin-angiotensin system (RAS) blockade were randomized to finerenone or placebo. Endpoints were change in UACR and a composite kidney outcome (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary cardiovascular outcomes (time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) (ClinicalTrials.gov, NCT02540993).ResultsOf 5674 patients, 259 (4.6%) received an SGLT-2i at baseline. Reduction in UACR with finerenone was found with or without use of SGLT-2i at baseline, with ratio of least-squares means of 0.69 (95% CI = 0.66–0.71) and 0.75 (95% CI -= 0.62–0.90), respectively (Pinteraction = 0.31). Finerenone also significantly reduced the kidney and key secondary cardiovascular outcomes versus placebo; there was no clear difference in the results by SGLT-2i use at baseline (Pinteraction = 0.21 and 0.46, respectively) or at any time during the trial. Safety was balanced with or without SGLT-2i use at baseline, with fewer hyperkalemia events with finerenone in the SGLT-2i group (8.1% vs. 18.7% without).ConclusionUACR improvement was observed with finerenone in patients with CKD and T2D already receiving SGLT-2is at baseline, and benefits on kidney and cardiovascular outcomes appear consistent irrespective of use of SGLT-2i.

189-OR: FIDELIO-DKD Study: Analysis of Effects of Finerenone by Baseline A1C

Introduction: Patients with CKD and T2D are at high risk of morbidity and mortality despite the use of guideline-directed therapies. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, reduced the risk of adverse kidney and CV outcomes in patients with CKD and T2D; here we report outcomes by baseline A1C. Methods: FIDELIO-DKD (NCT02540993) randomized 5734 patients from 48 countries to receive oral finerenone or placebo. Eligible patients had T2D, with a UACR of ≥30-≤5000 mg/g, eGFR ≥25‍-‍&amp;lt;75 mL/min/1.73 m2 and received optimized RAS blockade. Patients with A1C &amp;gt;12% at screening were excluded. The primary outcome was a composite of kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death. The key secondary outcome was a composite of CV death, non-fatal MI, non-fatal stroke, or hospitalization for HF. Results: In the 5674 patients analyzed, the mean baseline A1C was 7.7% and mean diabetes duration was 16.6 years; finerenone did not affect A1C during the trial. Overall, 2948 patients had A1C ≤7.5% and 2715 patients had A1C &amp;gt;7.5% at baseline. Patients with higher A1C levels were more likely to use insulin and had a longer duration of diabetes. After a median follow-up of 2.6 years, the primary outcome occurred in fewer patients treated with finerenone compared with placebo, this was observed in both the A1C ≤7.5% and &amp;gt;7.5% groups (18.7% vs. 21.5% patients with A1C of ≤7.5% [HR 0.86; 95% CI 0.73-1.01]; 16.9% vs. 20.7% patients with A1C &amp;gt;7.5% [HR 0.79; 95% CI 0.66-0.94]; P-interaction 0.47). Finerenone also reduced the incidence of the key secondary CV outcome compared with placebo regardless of baseline A1C (HR 0.88; 95% CI 0.71-1.07 for A1C ≤7.5% and HR 0.83; 95% CI 0.69-1.01 for A1C &amp;gt;7.5%; P-interaction 0.73). Reduction in UACR was consistent across subgroups. Overall, hyperkalemia events were independent of A1C level. Conclusion: In patients with CKD and T2D, treatment with finerenone reduced the risk for developing adverse kidney and CV outcomes independent of baseline A1C. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. M. Brinker: Employee; Self; Bayer AG, Stock/Shareholder; Self; Bayer AG. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck &amp; Co., Inc., Vascular Dynamics Inc. E. Burgess: Advisory Panel; Self; Bayer Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. P. Gillard: None. A. Joseph: Employee; Self; Bayer AG. Funding Bayer AG

405-P: Efficacy and Safety of Finerenone in Patients with CKD and T2D by Baseline Insulin Treatment

Introduction: Finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist that significantly reduced the risk of kidney and CV outcomes in patients with CKD and T2D in the FIDELIO-DKD trial, with no effect on blood glucose. In advanced T2D, insulin is often used to control glycemia. This analysis will report outcomes from the FIDELIO-DKD trial by baseline insulin treatment. Methods: In FIDELIO-DKD (NCT02540993), 5734 patients with T2D, UACR 30-5000 mg/g, eGFR 25-&amp;lt;75 mL/min/1.73 m2 and treated with optimized RAS blockade were randomized to oral finerenone or placebo. The primary outcome was a composite of kidney failure, a sustained ≥40% eGFR decline from baseline, or renal death. The key secondary outcome was a composite of CV death, non-fatal MI, non-fatal stroke, or hospitalization for HF. Results: Of the 5674 patients analyzed, 3637 (64.1%) were treated with insulin or insulin analogues at baseline. Patients treated with insulin at baseline had a higher A1C and a longer duration of diabetes, with higher proportions of statin and GLP-1RA use, and lower use of other anti-hyperglycemic agents than those who were not. Finerenone did not affect A1C during the trial. The primary and key secondary CV outcome occurred in fewer patients treated with finerenone, with no between-group interaction (primary outcome: HR 0.85, 95% CI 0.73-0.98 with insulin; HR 0.79, 95% CI 0.64-0.96 without insulin; P-value for interaction 0.56; CV outcome: HR 0.82, 95% CI 0.69-0.97 with insulin; HR 0.95, 95% CI 0.74-1.23 without insulin; P-value for interaction 0.33). Hyperkalemia events were similar between groups (mean treatment difference between finerenone and placebo for treatment-emergent serum potassium &amp;gt;5.5 mmol/L, 11.1% with insulin and 13.4% without insulin), with a low incidence of hyperkalemia-related treatment discontinuation. Conclusion: Finerenone has a beneficial effect on kidney and CV outcomes in patients with CKD and T2D, irrespective of insulin use at baseline. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. L. Roessig: Employee; Self; Bayer AG. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck &amp; Co., Inc., Vascular Dynamics Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. R. Macisaac: Advisory Panel; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Servier Laboratories, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk. J. Wainstein: Board Member; Self; Novo Nordisk, Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Kowa Company, Ltd., Speaker’s Bureau; Self; Novo Nordisk. A. Joseph: Employee; Self; Bayer AG. Funding Bayer AG

14-LB: Finerenone in Patients with CKD and T2D by SGLT2i Treatment: An Analysis of the FIDELIO-DKD Study

Introduction: The selective, nonsteroidal mineralocorticoid receptor antagonist finerenone was investigated in FIDELIO-DKD in patients with CKD and T2D (NCT02540993). Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are recommended for CKD in T2D to reduce risk of CKD progression. We report a predefined exploratory analysis of patients by SGLT-2i use. Methods: Patients (N=5674) with T2D, urine albumin-to-creatinine ratio (UACR) 30-5000 mg/g and estimated glomerular filtration rate (eGFR) 25-&amp;lt;75 mL/min/1.73 m2 receiving optimized RAS blockade were randomized to finerenone (10 mg daily increasing to 20 mg daily) or placebo. Results: Of 5674 patients, 259 (4.6%) received SGLT-2i at baseline. Overall, finerenone significantly reduced the primary (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) vs. placebo (p=0.001 and p=0.03, respectively) with no effect on A1C. Results were consistent irrespective of SGLT-2i use at baseline for the primary and key secondary CV outcomes (interaction p-value 0.21 and 0.46, respectively). Reduction in UACR with finerenone was seen without SGLT-2i use (ratio of LS-means 0.68, 0.65-0.71; p&amp;lt;0.0001) and on top of SGLT-2is at baseline (ratio of LS-means 0.75, 0.62-0.90; p=0.0024). Treatment-emergent hyperkalemia events were fewer with SGLT-2i vs. no SGLT-2i (post hoc analysis). Conclusion: The benefits of finerenone on kidney and CV outcomes in patients with CKD and T2D appear consistent in the absence or presence of SGLT2i, with UACR improvement observed in patients already receiving SGLT-2i at baseline. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. G. Schernthaner: None. C. Wanner: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, Speaker’s Bureau; Self; Eli Lilly and Company. A. Joseph: Employee; Self; Bayer AG. M. F. Scheerer: Employee; Self; AstraZeneca, Bayer AG, Stock/Shareholder; Self; Bayer AG, Eli Lilly and Company, Novo Nordisk A/S. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck &amp; Co., Inc., Vascular Dynamics Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. A. Kooy: Research Support; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Novo Nordisk, Sanofi-Aventis. K. Mccafferty: Advisory Panel; Self; AstraZeneca, Bayer AG, Napp Pharmaceuticals, Pharmacosmos, Vifor Pharma Management Ltd., Research Support; Self; AstraZeneca.

406-P: Efficacy and Safety of Finerenone in Patients with CKD and T2D by GLP-1RA Treatment

Introduction: Finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist that significantly reduced the risk of kidney and CV outcomes in patients with CKD and T2D in the FIDELIO-DKD trial. GLP-1RAs have also been shown to improve CV outcomes in patients with T2D as well as lowering albuminuria. The mechanism of action of finerenone and GLP-1RAs are largely independent but their combined effects are unknown. This analysis will report outcomes from the FIDELIO-DKD trial in patients by GLP-1RA treatment. Methods: FIDELIO-DKD (NCT02540993) randomized 5734 patients to oral finerenone or placebo. Patients with T2D, UACR 30-5000mg/g and eGFR 25-&amp;lt;75mL/min/1.73 m2, and treated with optimized RAS blockade, were included. The primary kidney outcome was time to kidney failure, sustained eGFR decline ≥40% from baseline, or renal death. Secondary outcomes included time to CV death, non-fatal MI, non-fatal stroke, or hospitalization for heart failure, and change in UACR from baseline to month 4. Results: Of the 5674 patients analyzed, 394 (6.9%) were treated with a GLP-1RA at baseline. Patients treated with GLP-1RAs at baseline had a higher BMI and A1C, with higher diuretic and statin use, lower median UACR and less presence of CVD than those who were not. There was no between-group interaction for the primary kidney (HR 1.17, 95% CI 0.71-1.90 with GLP-1RA; HR 0.80, 95% CI 0.71-0.91 without GLP-1RA; P-interaction 0.15) or secondary CV outcomes (HR 1.02, 95% CI 0.60-1.74 with GLP-1RA; HR 0.85, 95% CI 0.73-0.98 without GLP-1RA; P-interaction 0.51). The reduction in UACR was independent of GLP-1RA use (ratio of LS-means 0.63, 95% CI 0.56-0.70 with GLP-1RA; 0.69, 95% CI 0.67-0.72 without GLP-1RA; P-interaction 0.20). Overall, incidences of hyperkalemia events were similar in patients with and without GLP-1RA use. Conclusion: The effects of finerenone on kidney and CV outcomes appear consistent irrespective of GLP-1RA use, with a potential additive benefit for UACR reduction. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. A. Z. Lage: Employee; Self; Bayer Healthcare Pharmaceuticals Inc. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck &amp; Co., Inc., Vascular Dynamics Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. A. Amod: Advisory Panel; Self; Aspen South Africa, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Servier Laboratories, Consultant; Self; Servier Laboratories, Other Relationship; Self; Bayer AG, Merck Sharp &amp; Dohme Corp., Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Servier Laboratories. M. Marre: Board Member; Self; Merck Sharp &amp; Dohme Corp., Consultant; Self; Novo Nordisk. A. Joseph: Employee; Self; Bayer AG. Funding Bayer AG

Ambulatory Treatments for RAAS Inhibitor-Related Hyperkalemia and the 1-Year Risk of Recurrence.

The optimal ambulatory management of renin-angiotensin-aldosterone system inhibitor (RAASi)-related hyperkalemia to reduce the risk of recurrence is unknown. We examined the risk of hyperkalemia recurrence on the basis of outpatient pharmacologic changes following an episode of RAASi-related hyperkalemia. We performed a population-based, retrospective cohort study of older adults (n=49,571; mean age 79 years) who developed hyperkalemia (potassium ≥5.3 mEq/L) while on a RAASi and were grouped as follows: no intervention, RAASi discontinuation, RAASi dose decrease, new diuretic, diuretic dose increase, or sodium polystyrene sulfonate within 30 days. The primary outcome was hyperkalemia recurrence, with secondary outcomes of cardiovascular events and all-cause mortality within 1 year. Among patients who received a pharmacologic intervention (23% of the cohort), RAASi discontinuation was the most commonly prescribed strategy (74%), followed by RAASi decrease (15%), diuretic increase (7%), new diuretic (3%), and sodium polystyrene sulfonate (1%). A total of 16,977 (34%) recurrent hyperkalemia events occurred within 1 year. Compared with no intervention (35%, referent), the cumulative incidence of recurrent hyperkalemia was lower with RAASi discontinuation (29%; hazard ratio, 0.82; 95% confidence interval, 0.78 to 0.85), whereas there was no difference with RAASi dose decrease (36%; hazard ratio, 0.94; 95% confidence interval, 0.86 to 1.02), new diuretic (32%; hazard ratio, 0.95; 95% confidence interval, 0.78 to 1.17), or diuretic increase (38%; hazard ratio, 0.99; 95% confidence interval, 0.87 to 1.12) and a higher incidence with sodium polystyrene sulfonate (55%; hazard ratio, 1.30; 95% confidence interval, 1.04 to 1.63). RAASi discontinuation was not associated with a higher risk of 1-year cardiovascular events (hazard ratio, 0.96; 95% confidence interval, 0.91 to 1.02) or all-cause mortality (hazard ratio, 1.05; 95% confidence interval, 0.96 to 1.15) compared with no intervention. Among older adults with RAASi-related hyperkalemia, RAASi discontinuation is associated with the lowest risk of recurrent hyperkalemia, with no apparent increase in short-term risks for cardiovascular events or all-cause mortality.

Association between antihypertensive treatment and adverse events: systematic review and meta-analysis

ObjectiveTo examine the association between antihypertensive treatment and specific adverse events.DesignSystematic review and meta-analysis.Eligibility criteriaRandomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs...

Risk factors associated with the incidence and recurrence of hyperkalaemia in patients with cardiorenal conditions.

Hyperkalaemia (HK) is associated with increased mortality risk. Prior studies suggest that the causes of HK are multifactorial. This study aimed to examine risk factors for incident and recurrent HK in six large real-world cohorts of UK patients that could be considered at elevated HK risk because of underlying disease pathology and/or medication use. This retrospective, observational cohort study utilised UK primary and secondary care data from Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES), respectively. Patients were included if they were aged ≥18years and had a record of ≥1 condition of interest (chronic kidney disease [CKD] stage 3+, heart failure, resistant hypertension [RHTN], dialysis, diabetes) and/or renin-angiotensin-aldosterone system inhibitors (RAASi) use between 01 January 2003 and 30 June 2018. Based on their diagnosis/ RAASi prescription record, patients were assigned to overlapping cohorts. The outcomes assessed were HK and recurrent HK, the latter defined as second or subsequent HK episode during follow-up. HK was defined as a serum K+ measurement ≥5.0mmol/L; thresholds of ≥5.5 and≥6.0mmol/L were also explored. Of 931460 meeting the eligibility criteria, 310535 (33.3%) patients experienced ≥1 HK event and 187719 (20.2%) experienced HK recurrence. The probability of subsequent HK events increased with event number from 60.5% for the second event to 76.5% for the sixth and the corresponding time to the next HK event decreased from 15.8months to 6.1months. Amongst the key risk factors, serum creatinine, serum phosphorus, systolic blood pressure, and white cell count demonstrated direct relationships with incidence and recurrence of HK, while inverse relationships were observed for estimated glomerular filtration rate (eGFR), haemoglobin and diastolic blood pressure. The relationship for Charlson's Comorbidity Index was mixed. The use of RAASi and anti-hyperglycaemic agents was associated with an increased risk of HK, while the use of diuretics (non-K+ -sparing) was protective against HK. Several risk factors for HK that are easily measured in routine clinical practice were identified, facilitating the identification of patients who are at the highest risk of experiencing HK, including recurrent HK.