Rate Of Hyperkalemia Research Articles

FC084: Mineralocorticoid Receptor Antagonist Treatment in Patients with Renal Insufficiency and Associated Risk of Hyperkalemia and Death

Abstract BACKGROUND AND AIMS Mineralocorticoid receptor antagonist treatment is kidney protective but not recommended in patients with advanced renal failure due to perceived risk of hyperkalaemia and death. The aim of the present study was to examine the impact of mineralocorticoid receptor antagonist treatment in progressive chronic kidney disease on risk of hyperkalaemia and to evaluate subsequent attributable mortality. METHOD Based on data from multiple nationwide health care registers, all Danish residents >18 years with more than or equal to one recorded plasma creatinine measurement were identified in Denmark between 2008 and 2021, and followed until either incident hyperkalaemia >6 mmol/L, death or end-of follow-up (5 October 2021). Cases were identified based on incident hyperkalaemia and subsequently matched with four controls without hyperkalaemia. eGFR was computed based on the latest creatinine measurement until 30 days prior to index using the CKD-EPI equation. Patients with no recorded creatinine measurement within 2 years until 30 days prior of index were excluded. Mineralocorticoid receptor antagonist associated susceptibility for hyperkalaemia was computed across strata of estimated glomerular filtration rate (eGFR) (>60, 30–60 and <30 mL/min/1.73 m2) in a conditional logistic regression model comparing rate of hyperkalaemia with stratification of baseline hazard rate by age, gender, diabetes and hypertension. Model fitting was accomplished using a nested case–control design with 1:4 risk-set matching of cases with age-, gender-, diabetes- and hypertension-matched controls. Subsequent risk of 30-day mortality was assessed in a retrospective cohort study including patients with hyperkalemia only. Patients were followed from the date of hyperkalemia until death, 30 days or end of follow-up (5 October 2021) with comparison of MRA-attributable mortality across strata of eGFR based on the Kaplan–Meier estimator and multiple Cox regression models adjusted for age and gender. RESULTS From a population of 4 255 962 Danish citizens with recorded plasma creatinine, a total of 51 775 patients with incident hyperkalaemia were identified between 2008 and 2021. Pre-existing plasma creatinine permitting estimation of renal function was available in 34 442 (66.5%) patients. The 34 442 cases with incident hyperkalaemia were matched 1:4 with 131 410 controls. Gender distribution was 57% male, median age was 73.5 (IQR 64.0–82.0) years and median eGFR was 74 (IQR 55–89) mL/min/1.73 m2. Mineralocorticoid receptor antagonist treatment was associated with increased rates of hyperkalaemia with HRs of 8.32 (95% CI: 7.82–8.85), 4.55 (95% CI: 4.26–4.86) and 2.00 (95% CI: 1.71–2.32) in patients with eGFR > 60 mL/min/1.73 m2 eGFR 30–60 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2 respectively (reference = No mineralocorticoid receptor antagonist treatment). 30-day mortality in patients with hyperkalaemia stratified on mineralocorticoid receptor antagonist treatment is shown in Figures 1 and 2. Overall, mineralocorticoid receptor antagonist treatment was associated with lower subsequent mortality: HR 0.84 (95% CI: 0.78–0.90); P < 0.001, 0.67 (95% CI: 0.62–0.73); P < 0.001 and 0.98 (95% CI: 0.86–1.1); P = 0.77 for eGFR > 60 mL/min/1.73 m2 30–60 mL/min/1.73 m2 and <30 mL/min/1.73 m2 respectively (reference = mineralocorticoid receptor antagonist). CONCLUSION Although mineralocorticoid receptor antagonist treatment was associated with increased risk of hyperkalaemia for all strata of kidney impairment, subsequent 30-day mortality was lower compared with patients with corresponding kidney function without mineralocorticoid receptor antagonist treatment.

Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease.

People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared with the general population, and this may alter the usual creatinine-based eGFR cutoffs for which physiologic evidence of kidney dysfunction is apparent. This study aimed to identify eGFR thresholds for hyperkalemia and metabolic acidosis in patients with SCD. This was a cross-sectional analysis of 733 patients with severe (hemoglobin SS or Sβ0-thalassemia) SCD genotype, 238 patients with moderate (hemoglobin SC or Sβ+-thalassemia) SCD genotype, and 1333 age- and sex-matched African Americans from the National Health and Nutrition Examination Survey (NHANES). The prevalence rates of hyperkalemia and metabolic acidosis were compared by eGFR category. Cutoffs for hyperkalemia and metabolic acidosis were determined using generalized additive models. Hyperkalemia and metabolic acidosis were more common in those with severe SCD genotype (13% and 21%, respectively) compared with the NHANES (0.3% and 5%, respectively); the prevalence rates in the moderate SCD genotype were intermediate for hyperkalemia (3%) and metabolic acidosis (11%). The proportion of patients with hyperkalemia and metabolic acidosis progressively increased with lower eGFR category in both SCD genotype groups. The eGFR thresholds for hyperkalemia and metabolic acidosis were higher in the severe (85 and 91 ml/min per 1.73 m2, respectively) and moderate (52 and 102 ml/min per 1.73 m2, respectively) SCD genotypes compared with the NHANES (34 and 46 ml/min per 1.73 m2). We demonstrate that hyperkalemia and metabolic acidosis are more common and occur at higher eGFR values in patients with SCD compared with age- and sex-matched African Americans, including in eGFR ranges considered to be normal. Future studies using redefined creatinine-based eGFR thresholds for abnormal kidney function may identify high-risk patients for earlier intervention strategies and referral for specialized renal care in SCD.

Clinical safety and outcomes of glucagon use during endoscopic retrograde cholangiopancreatography (ERCP).

Background and study aims Injectable glucagon enables easier biliary cannulation by inhibiting gastrointestinal motility and decreasing the frequency and amplitude of phasic activity of the sphincter of Oddi during endoscopic retrograde cholangiopancreatography (ERCP). Data about the safety profile of glucagon use and patient clinical outcomes are scarce. Patients and methods We used a federated cloud-based network research database, TriNetX, comprising 92 US healthcare organizations to find adult patients undergoing ERCP with glucagon use (Group A) vs. without using glucagon (Group B) from August 1, 2010, to August 1, 2021. The primary outcomes were rates of gastrointestinal bleeding, gastrointestinal perforation, post-ERCP pancreatitis, inpatient hospitalizations, and 30-day overall mortality measured after 1:1 propensity matching of the groups based on the baseline demographics and comorbidities. Results There were 9,008 patients in Group A compared to 256,597 in Group B. After matching, Group A patients had lower rates of gastrointestinal bleeding (risk ratio [RR], 0.68; CI, 0.52–0.86), post-ERCP pancreatitis (RR, 0.64; CI, 0.58–71), inpatient hospitalization (RR 0.34; CI:0.32 to 0.36) and overall mortality (RR, 0.81; CI, 0.66–0.99). The rates of gastrointestinal perforation (RR, 0.64; CI: 0.34 to 1.19), hyperkalemia (RR, 0.83; CI, 0.64–1.09) and hyperglycemia (RR, 0.65; CI, 0.41–1.03) did not differ between the two groups. Discussion Glucagon use during ERCP was associated with low rates of gastrointestinal bleeding, post-ERCP pancreatitis, inpatient hospitalization, and overall mortality. Moreover, the rates of hyperkalemia and hyperglycemia did not differ between the two groups even after matching for diabetes, indomethacin use, obesity, and chronic kidney disease.

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.

POS-627 INVESTIGATION ON THE SEASONAL DISTRIBUTION OF HYPERKALEMIA IN HEMODIALYSIS PATIENT

Cardiovascular disease is the main cause of death of hemodialysis patients. USRDS suggests that cardiovascular events, especially arrhythmia and cardiac arrest account for more than 1 / 3 of hemodialysis patients. Hyperkalemia is an important and intervenable factor of cardiac arrest. At present, there is a lack of epidemiological data on hyperkalemia in hemodialysis patients in China, especially in the western region. Therefore, the purpose of this study is to investigate the prevalence and time variations of hyperkalemia, as well as the detection rate of hyperkalemia with different detection times, to provides an important reference for the prevention, treatment and research of hyperkalemia.

Dyskalemia risk associated with fixed-dose anti-hypertensive medication combinations.

A model-based meta-analysis quantified comparative dyskalemia risk (hyper- or hypo-kalemia) in hypertensive patients treated with angiotensin receptor blockers (ARBs), a calcium channel blocker (CCB) and/or a thiazide diuretic (hydrochlorothiazide; HCTZ) as monotherapy or as fixed-dose combinations. Among 15 randomized controlled trials in a US Food and Drug Administration regulatory review database, dyskalemia events were reported by five trials (24 treatment arms, 11,030 subjects, 8-week median follow up time). The five trials evaluated monotherapy (ARB or HCTZ) alongside dual (ARB + HCTZ, ARB + CCB, or HCTZ + CCB) or triple fixed-dose combinations (ARB + CCB + HCTZ). Hypo- and hyper-kalemia rates were analyzed jointly to account for correlation. Significant drug class, drug, or dose effects were included in the final model. Effect on various drug- and dose combinations on dyskalemia risk were simulated and compared with model-estimated placebo arm dyskalemia risk. After a typical follow-up of 8 weeks, fixed-dose combinations of ARB with a high dose (25 mg) of HCTZ were associated with a higher hypokalemia risk difference (RD) from placebo (e.g.,Valsartan + HCTZ: 2.52%[95%CIs:1.17, 4.38%]). However, when ARB was combined with a lower, 12.5 mg dose of HCTZ, hypokalemia RD from placebo was not significant (Valsartan + HCTZ: -0.03%[-0.80, 0.71%]). ARB monotherapy raised hyperkalemia RD from placebo (1.3%[0.3, 3.6%]). Hyperkalemia risk was not appreciably higher than placebo for any FDC that combined ARB with HCTZ (Valsartan + HCTZ: 0.06%[-1.48, 1.64%]). In uncomplicated hypertensive patients, ARB + 12.5 mg HCTZ fixed-dose combinations are safer with respect to dyskalemia than either ARB or HCTZ monotherapy for initial antihypertensive treatment.

Efficacy and safety of dual vs single renin-angiotensin-aldosterone system blockade in chronic kidney disease: An updated meta-analysis of randomized controlled trials.

Background:To lower albuminuria and to achieve blood pressure (BP) goals, dual renin–angiotensin–aldosterone system (RAAS) inhibitors are sometimes used in clinical practice for the treatment of CKD. However, the efficacy and safety of dual RAAS blockade therapy remains controversial.Methods:PubMed, EMBASE, and Cochrane Library were searched, and random effects model was used to calculate the effect sizes of eligible studies. Potential sources of heterogeneity were detected by meta-regression and subgroup analysis.Results:The present meta-analysis of 72 randomized controlled trials with 10,296 patients demonstrated that dual RAAS blockade therapy was superior to monotherapy in reducing the urine albumin excretion, urine protein excretion, and BP. These beneficial effects were related to the decrease of glomerular filtration rate, the increase of serum potassium level, and higher rates of hyperkalemia and hypotension. Meanwhile, these effects did not lead to improvements in short-term or long-term outcomes, including doubling of serum creatinine, acute kidney injury, end-stage renal disease, mortality, and hospitalization. Compared with the single therapy, angiotensin-converting enzyme inhibitor (ACEI) in combination with angiotensin-receptor blocker (ARB) was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist in decreasing urine albumin excretion, urine protein excretion and BP, and the combination was not associated with a lower glomerular filtration rate.Conclusion:Compared with the single therapy, ACEI in combination with ARB was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist. Although ACEI in combination with ARB was associated with higher incidences of hyperkalemia and hypotension, careful individualized management and potassium binders may further expand its application (PROSPERO number CRD42020179398).

Population Epidemiology of Hyperkalemia: Cardiac and Kidney Long-term Health Outcomes

The population burden and long-term implications of hyperkalemia have not been comprehensively studied. We studied how often and where hyperkalemia occurs as well as its independent association with survival and long-term cardiac and kidney health. Population-based cohort study of adult residents of Grampian, United Kingdom. Among the 468,594 adult residents (2012-2014), 302,630 people with at least 1 blood test were followed until2019. Hyperkalemia was defined as serum potassium≥ 5.5 mmol/L. Adjustment for comorbidities, demographics, measures of acute and chronic kidney function, and medications prescribed before measurement of serum potassium. All-cause mortality, cardiac events, and kidney failure. Description of the annual incidence of hyperkalemia and the characteristics associated with its occurrence, and adjusted Cox proportional hazards (PH) analysis to evaluate theindependent long-term association of hyperkalemia with all-cause mortality among people who survived≥90 days after blood testing. Cause-specific PH models were fit to evaluate the association of hyperkalemia with cardiac events/death, noncardiac death, and kidney failure. Effect modification by level of estimated glomerular filtration rate (eGFR) at the time of blood testing was explored. The annual population incidence of hyperkalemia was 0.96 per 100 person-years. This represented 2.3%, 2.1%, and 1.9% of people with at least one blood test in 2012, 2013, and 2014, respectively. Two-thirds of episodes of hyperkalemia occurred in the community. The hyperkalemia rate was 2-fold higher for each 10-year greater age. Those with hyperkalemia were 20 times more likely to have concurrent acute kidney injury (AKI), and 17 times more likely to have an eGFR of<30 mL/min/1.73 m2. Throughout 5 years of follow-up evaluation (2,483,452 person-years), hyperkalemia was associated with poorer health outcomes. This association held across all levels of kidney function and was irrespective of concurrent AKI, but was stronger among those with a baseline eGFR of≥60 mL/min/1.73 m2 (P for interaction< 0.001). The adjusted HRs (hyperkalemia vs no hyperkalemia) for people with eGFR≥60 mL/min/1.73 m2 and eGFR<30 mL/min/1.73 m2 were 2.3 (95% CI, 2.2-2.5) and 1.5 (95% CI, 1.3-1.6) for mortality; 1.8 (95% CI, 1.6-1.9) and 1.4 (95% CI, 1.2-1.6) for cardiac events; and 17.0 (95% CI, 9.3-31.1) and 2.0 (95% CI, 1.5-2.8) for kidney failure, respectively. The observational nature of this study limits evaluation of causal relationships. There is a substantial burden of hyperkalemia in the general population. Hyperkalemia is associated with poorer long-term health outcomes, especially kidney outcomes, that are independent of other established risk factors.

Association between the use of balanced fluids and outcomes in critically ill children: a before and after study

BackgroundHyperchloremia and chloride load have been associated with worse clinical outcomes in critically ill patients. We sought to evaluate the electrolyte profile and clinical outcomes associated with a unit-wide transition from saline to balanced fluids for resuscitation and maintenance fluids in a pediatric intensive care unit (PICU).MethodsA before and after analysis of all patients admitted to the PICU in a large, urban, academic hospital between August 2018 and March 2020. The transition from the use of saline to the use of balanced fluids for both resuscitation and maintenance fluid as standard care occurred in June 2019. The primary outcome was day 3 acute kidney injury (AKI). The secondary outcomes included mortality, ventilator-free days (VFDs), need for renal replacement therapy (RRT), hospital length of stay (LOS), and electrolyte abnormalities.ResultsOverall, 2863 patients (47% female) with a day 3 AKI rate of 12.9% (n = 130) and a mortality rate of 2.8% (n = 79) were included. After adjusting for confounders (age, PRISM III, mechanical ventilation, and immunocompromised state, septic shock), there were no significant differences in the odds of day 3 AKI (pre 13%, post 12.5%; adjusted odds ratio [aOR] 0.96, 95%CI 0.65–1.42). There were no differences in the secondary outcomes. The post-intervention period had fewer patients with hyperchloremia (pre 15.5% vs. post 10.4%, p = < 0.0001) and hyperkalemia (pre 3.2% vs. post 1.4%, p = 0.02) and more patients with hypochloremia (pre 9.5% vs. post 14.4%, p = < 0.0001) and hypokalemia (pre 38.2% vs. post 47.2%, p = < 0.0001). In reference to the normochloremic cohort, the hypochloremic cohort had an increase in day 3 AKI, need for RRT, hyperchloremia, and hyperkalemia, and a decrease in hypokalemia; and the hyperchloremic cohort had an increase in VFD and a decrease in hospital LOS.ConclusionsFollowing a unit-wide implementation of balanced fluids as standard care, there were no differences in rates of day 3 AKI or other clinical outcomes. However, there were lower rates of hyperkalemia and hyperchloremia and higher rates of hypokalemia and hypochloremia. Further evaluation of the effect of balanced fluids and the clinical significance of electrolyte abnormalities in critically ill children is needed.

Spironolactone Improves the All-Cause Mortality and Re-Hospitalization Rates in Acute Myocardial Infarction with Chronic Kidney Disease Patients.

Background: Mineralocorticoid receptor antagonists (MRA) improve outcomes in chronic kidney disease (CKD) and acute myocardial infarction (AMI) patients. However, the lack of evidence regarding long-term clinical outcomes in the use of MRA, including spironolactone, in patients with AMI combined with CKD. Objectives: This study aimed to investigate whether spironolactone could significantly reduce the risk of all-cause mortality and re-admission in patients with AMI and CKD. Methods: In this single center, observational, retrospective, registry based clinical study, a total of 2,465 AMI patients were initially screened; after excluding patients with estimated glomerular filtration rate more than 60 ml/min/1.73 m2, 360 patients in the standard treatment group and 200 patients in the spironolactone group met the criteria. All enrolled patients follow-up for 30 months. The primary outcomes were all-cause mortality and re-admission. The key safety outcome was hyperkalemia rates during the 30 months follow-up period. Results: 160 (44.4%) and 41 (20.5%) patients in the standard treatment and spironolactone groups died, respectively [hazard ratio (HR): 0.389; 95% confidence interval (CI): 0.276–0.548; p < 0.001]. Re-admission occurred in 217 (60.3%) and 95 (47.5%) patients in the standard treatment and spironolactone groups, respectively (HR: 0.664; 95% CI: 0.522–0.846; p = 0.004). The spironolactone group was divided into two based on the daily dose, low dose group (no more than 40 mg) and high dose group (more than 40 mg); the differences in the mortality rate between low dose group (16.7%) and the standard treatment group (44.4%) (HR: 0.309; 95% CI: 0.228–0.418; p < 0.001) and high dose group (34.1%) (HR: 0.429; 95% CI: 0.199–0.925; p = 0.007) were significant. The differences in re-hospitalization rate between low dose group (43.6%) and the standard treatment group (60.3%) (HR: 0.583; 95% CI: 0.457–0.744; p < 0.001) and high dose group (61.4%) (HR: 0.551; 95% CI: 0.326–0.930; p = 0.007) was significant. Hyperkalemia occurred in 18 (9.0%) and 18 (5.0%) patients in the spironolactone group and standard treatment group, respectively (HR: 1.879; 95% CI: 0.954–3.700; p = 0.068). Whereas, Hyperkalemia occurred in high dose group (20.5%) significantly more often than in the standard treatment group (p < 0.001) and low dose group (5.8%) (p = 0.003). Conclusion: Using MRA, such as spironolactone, may substantially reduce the risk of both all-cause mortality and re-admission in patients with AMI and CKD; the use of low-dose spironolactone has the best efficacy and safety. However, this was a relatively small sample size, single center, observational, retrospective, registry based clinical study and further prospective evaluation in adequately powered randomized trials were needed before further use of spironolactone in AMI with CKD population.

Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitor in Combination with Angiotensin-Receptor Blocker in Chronic Kidney Disease Based on Dose: A Systematic Review and Meta-Analysis.

Background: The purpose of this meta-analysis was to evaluate the controversy of angiotensin-converting enzyme inhibitor (ACEI) in combination with angiotensin-receptor blocker (ARB) in the treatment of chronic kidney disease (CKD) based on dose. Methods: PubMed, EMBASE, and Cochrane Library were searched to identify randomized controlled trials (RCTs) from inception to March 2020. The random effects model was used to calculate the effect sizes. Potential sources of heterogeneity were detected using sensitivity analysis and meta-regression. Results: This meta-analysis of 53 RCTs with 6,375 patients demonstrated that in patients with CKD, ACEI in combination with ARB was superior to low-dose ACEI or ARB in reducing urine albumin excretion (SMD, −0.43; 95% CI, −0.67 to −0.19; p = 0.001), urine protein excretion (SMD, −0.22; 95% CI, −0.33 to −0.11; p < 0.001), and blood pressure (BP), including systolic BP (WMD, −2.89; 95% CI, −3.88 to −1.89; p < 0.001) and diastolic BP (WMD, −3.02; 95% CI, −4.46 to −1.58; p < 0.001). However, it was associated with decreased glomerular filtration rate (GFR) (SMD, −0.13; 95% CI, −0.24 to −0.02; p = 0.02) and increased rates of hyperkalemia (RR, 2.07; 95% CI, 1.55 to 2.76; p < 0.001) and hypotension (RR, 2.19; 95% CI, 1.35 to 3.54; p = 0.001). ACEI in combination with ARB was more effective than high-dose ACEI or ARB in reducing urine albumin excretion (SMD, −0.84; 95% CI, −1.26 to −0.43; p < 0.001) and urine protein excretion (SMD, −0.24; 95% CI, −0.39 to −0.09; p = 0.002), without decrease in GFR (SMD, 0.02; 95% CI, −0.12 to 0.15; p = 0.78) and increase in rate of hyperkalemia (RR, 0.94; 95% CI, 0.65 to 1.37; p = 0.76). Nonetheless, the combination did not decrease the BP and increased the rate of hypotension (RR, 3.95; 95% CI, 1.13 to 13.84; p = 0.03) compared with high-dose ACEI or ARB. Conclusion: ACEI in combination with ARB is superior in reducing urine albumin excretion and urine protein excretion. The combination is more effective than high-dose ACEI or ARB without decreasing GFR and increasing the incidence of hyperkalemia. Despite the risk of hypotension, ACEI in combination with ARB is a better choice for CKD patients who need to increase the dose of ACEI or ARB (PROSPERO CRD42020179398).

Hyperkalemia in chronic heart failure with renal dysfunction or diabetes mellitus: Results from the TREAT HF study.

Chronic kidney disease (CKD) and diabetes mellitus (DM) are common comorbidities in heart failure (HF). Patients with HF are at a high risk of hyperkalemia, and are therefore undertreated with respect to disease-modifying therapies. The Turkish Research Team-Heart Failure (TREAT HF) data were analyzed for the evaluation of hyperkalemia in real-life clinical practice in HF patients with CKD or DM. The TREAT HF is a multicenter, national, observational registry. In this study, potassium levels of 1028 patients with HF were analyzed. Hyperkalemia is defined as blood potassium levels >5 mEq/L and evaluated based on the CKD, DM, HF medications, and New York Heart Association (NYHA) classes. Overall, 14.3% of patients (n=147) were found to have hyperkalemia. Hyperkalemia was more prevalent in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 than those with eGFR ≥60 mL/min/1.73 m2 (17.7% and 12%, respectively, p=0.010). Hyperkalemia was present in 10.9% (n=23) of patients with stage 1, 12.6% (n=50) with stage 2, 17.0% (n=52) with stage 3, and 19.5% (n=22) with stage 4-5 CKD. Hyperkalemia was higher in patients with DM (20.5% vs 12.3%, p=0.001). Furthermore, hyperkalemia was much higher in patients with DM with eGFR <60 mL/min/1.73 m2 (25.2%). The rate of hyperkalemia increased across NYHA categories (NYHA-I: 9.8%, NYHA-II: 12.8%, NYHA-III: 14.4%, and NYHA-IV: 23.4%, p=0.030). In patients with stage 4-5 CKD who were receiving renin-angiotensin-aldosterone system (RAAS) inhibitor therapy, more patients had hyperkalemia than those not receiving RAAS inhibitor therapy (23.4% and 12.5%, respectively). In clinical practice, 14.3% of all patients with HF, 17.7% of all patients with CKD, and 20.5% of all patients with DM have hyperkalemia. The risk of hyperkalemia increases with advanced stages of CKD or NYHA and the risk is higher in patients receiving RAAS inhibitor therapy.

Onset of Hyperkalemia following the Administration of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker.

Introduction In spite of the established importance of detecting angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker- (ARB-) induced hyperkalemia, there have not been many studies on the time of its occurrence. Methods We retrospectively analyzed electronic medical records to determine the onset time and incidence rate of hyperkalemia (serum potassium > 5.5 mEq/L or 6.0 mEq/L) among hospitalized patients newly started on a 15-day ACEI or ARB therapy. Results Among 3101 hospitalized patients, hyperkalemia incidence was 0.5%–0.9% and 0.8%–2.1% in the ACEI and ARB groups, respectively. However, it was not significantly different among different ARB types. Hyperkalemia's onset was distributed throughout 15 days, without any trend. Hyperkalemia incidence was 7.3 and 35.1 times higher at 5.5 mEq/L (hazard ratio (HR) = 7.31, 95%confidence interval (CI) = 4.19–12.76, p < 0.001) and 6.0 mEq/L (HR = 35.11, 95%CI = 8.25–149.52, p < 0.001), respectively, than the baseline creatinine level. Hyperkalemia incidence in patients with chronic renal failure was 5.7 and 9.2 times higher at 5.5 mEq/L (HR = 5.72, 95%CI = 3.24–10.12, p < 0.001) and 6.0 mEq/L (HR = 9.16, 95%CI = 4.02–20.88, p < 0.001), respectively. Conclusions It is unlikely that it is necessary to monitor hyperkalemia immediately after administration of ACEI or ARB. However, when prescribed for patients with abnormal kidney function, clinicians should always consider the possibility of developing hyperkalemia.

Hyperkalemia and Acute Kidney Injury with Spironolactone Use Among Patients with Heart Failure

ObjectiveTo quantify the risk of hyperkalemia and acute kidney injury (AKI) when spironolactone use is added on to loop diuretic use among patients with heart failure, and to evaluate whether the risk is modified by level of kidney function. MethodsWe identified 17,110 patients with heart failure treated with loop diuretics between January 1, 2004, and December 31, 2016 within the Geisinger Health System. We estimated the incidence of hyperkalemia and AKI associated with spironolactone initiation, and used target trial emulation methods to minimize confounding by indication. ResultsDuring a mean follow-up of 134 mo, 3229 of 17,110 patients (18.9%) initiated spironolactone. Incidence rates of hyperkalemia and AKI in patients using spironolactone with a loop diuretic were 2.9 and 10.1 events per 1000 person-months, respectively. In propensity score–matched analyses, spironolactone initiation was associated with higher hyperkalemia and AKI risk compared with loop alone (hazard ratio, 1.69; 95% CI, 1.35 to 2.10; P<.001, and hazard ratio, 1.12; 95% CI, 1.00 to 1.26; P=.04, respectively). There were no differences in the relative risk of either outcome associated with spironolactone by level of kidney function. ConclusionThe addition of spironolactone to loop diuretics in patients with heart failure was associated with higher risk of hyperkalemia and AKI; these risks must be weighed against the potential benefits of spironolactone.

Effects of canagliflozin on serum potassium in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program.

BackgroundThe sodium-glucose cotransporter 2 inhibitor canagliflozin has been shown to reduce the risk of cardiovascular and renal events in patients with Type 2 diabetes mellitus and high risk. Pooled analyses of data from early studies and interim data from the CANagliflozin cardioVascular Assessment Study (CANVAS) suggested that canagliflozin might lead to increases in serum potassium, particularly the 300 mg dose in patients with renal impairment, which is important because high serum potassium is associated with increased cardiovascular and renal risk. We examined the effect of canagliflozin on serum potassium levels and hyperkalemia rates in the completed CANVAS Program. MethodsThe CANVAS Program (n = 10,142) was comprised of two comparable double-blind, randomized, placebo-controlled trials (CANVAS and CANVAS-Renal). Participants received canagliflozin 100 or 300 mg or placebo. Serum potassium measurements were performed in a central laboratory0 and assessed at ∼6-month intervals. ResultsIn the CANVAS Program, mean potassium levels were generally consistent with canagliflozin and placebo, overall and by baseline estimated glomerular filtration rate (eGFR; ≥60, 45 to<60 and <45 mL/min/1.73 m2). The risk of increased or decreased potassium was similar with canagliflozin and placebo overall and by baseline eGFR (all P-heterogeneity ≥0.56) or use of renin–angiotensin–aldosterone system inhibitors (all P-heterogeneity ≥0.71); levels did not appear different by canagliflozin dose. Hyperkalemia {hazard ratio (HR) [95% confidence interval (CI)] 1.60 (0.92–2.81)} and serious hyperkalemia [HR (95% CI) 0.75 (0.27–2.11)] adverse events were not different across groups. ConclusionsIn the CANVAS Program, there were no meaningful effects of canagliflozin on serum potassium in the overall population or key subgroups. Hyperkalemia adverse events were uncommon and occurred at comparable rates with canagliflozin and placebo.

Direct Renin Inhibition in Non-diabetic chronic Kidney disease (DRINK): a prospective randomized trial.

The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients. In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3-4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis. Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm. Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.

P0671THE ASSOCIATION BETWEEN HYPERKALAEMIA RISK AND CARDIOVASCULAR AND RENAL COMORBIDITIES IN A LARGE REAL-WORLD COHORT OF CKD PATIENTS

Abstract Background and Aims Approximately 275.9 million people globally and 5.6 million people in the UK are living with chronic kidney disease (CKD). The risk of hyperkalaemia (HK) is elevated in CKD due to renal impairment and may increase further upon treatment with renin-angiotensin-aldosterone system inhibitors, which are commonly used in many cardiovascular and renal conditions. This study aimed to assess the relationship between comorbidity burden and HK risk in a large cohort of UK CKD patients. Method Primary and secondary care data from the UK Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) were used to identify patients aged ≥18 years who had a diagnosis of stage 3+ CKD (identified as either a READ code for non-dialysis CKD stage 3+ or an estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73m2 without a prior READ code for dialysis) during the study period (2008–June 2018) or the five-year look-back period (2003–2007). Patient’s index date was 1st January 2008 or the first date of CKD diagnosis, whichever occurred later. Diagnoses based on the presence of READ codes were used to define the accumulation of further cardiovascular or renal comorbidities of interest (resistant hypertension, heart failure, diabetes or dialysis-dependent CKD). The incidence of HK was defined as serum potassium (K+) thresholds of ≥5.0, ≥5.5 and ≥6.0 mmol/L. Results In total, 297,702 eligible patients had a CKD diagnosis during the study or look back periods and their mean follow-up was 5.6 (SD 3.2) years from index date. At baseline, mean age was 74.7 (11.3) years, mean body mass index was 28.3 (5.9) kg/m2, and 58.6% of patients were female. CKD was the first diagnosis in 169,532 patients (56.9% of all CKD diagnoses), second diagnosis in 92,651 patients (31.1%), third in 32,606 patients (11.0%) and fourth or fifth in 2,913 patients (1.0%); however, only 11,129 CKD patients (3.74%) developed four or more comorbidities of interest. In total, 1.5% of the cohort (4,544 patients) progressed to dialysis and 29.6% (88,245 patients) died during the study period. In general, the incidence of HK increased with the number of comorbidities of interest (Figure 1). At a K+ threshold of ≥5.0 mmol/L, crude incidence rate of HK was 286.5 (95% CI: 285.2–287.8) per 1,000 patient-years in patients with CKD only; this increased 2.8-fold to 806.8 (741.5–876.4) in patients with five comorbidities of interest. A similar trend was observed at K+ thresholds of ≥5.5 mmol/L and ≥6.0 mmol/L. A 5.9 fold increase was observed in crude incidence rate of HK (from 59.7 [59.1–60.3] with CKD only, to 350.3 [307.7–397.1] with all five comorbidities) at a threshold of ≥5.5 mmol/L and a 10.6-fold increase (from 9.1 [8.9–9.4] to 96.2 [74.6–122.2]) at the ≥6.0 mmol/L threshold. Conclusion This assessment of a large real-world patient cohort showed that the risk of HK in patients with CKD increases with the number of cardiovascular or renal comorbidities. Emphasis should be put on effective prevention and treatment of HK in CKD, especially in patients with high comorbidity burden.

P0799EPIDEMIOLOGY AND TREATMENT PATTERN OF HYPERKALAEMIA AMONG OUTPATIENTS IN CHINA: A DESCRIPTIVE STUDY USING AN ADMINISTRATIVE DATABASE IN CHINA

Abstract Background and Aims At present, the clinical burden and treatment pattern of hyperkalaemia among outpatients in China is not well characterized. The aim of this study was to evaluate the disease distribution and treatment pattern of hyperkalaemia among outpatients in China. Method Data were derived from Beijing Data Center for Rational Use of Drugs, which contains primary records of 157 hospitals, covering 30 provinces in China. Patients who accessed outpatients (aged &amp;gt;=≥18 years old) with record(s) of serum potassium (S-K) between 2015.1.1- 2017.12.31 were included. The laboratory test, diagnoses, and treatments were analyzed. Hyperkalaemia defined as S-K &amp;gt; 5.0 mmol/L. A hyperkalaemia episode was defined as one or more consecutive S-K &amp;gt; 5.0mmol/L measurement(s) within 7 days. If there was a return to S-K &amp;lt;5.0mmol/L within 7 days, the subsequent measurement(s) will be recognized as another hyperkalaemia episode. The proportion of hyperkalaemia was defined as the proportion of patients who experienced at least one hyperkalaemia episode. The main outcomes, including the proportion of hyperkalaemia patients, the diagnosis rate, the treatment rate and the S-K retesting rate were analyzed. The geographic and seasonal distribution of the proportion was examined. The diagnosis rate was defined as the proportion of hyperkalaemia episodes that have diagnoses records of hyperkalaemia within the episode. Treatment rate was defined as the proportion of hyperkalaemia episodes that have records of any hyperkalaemia treatment including diuretics, glucose injection + insulin, calcium injection, sodium bicarbonate, potassium binder, transfer to emergency room or dialysis. Retesting rate was defined as the proportion of hyperkalaemia records that have potassium test record(s) within one day, two days or seven days. Results A total of 2,997,634 patients with at least one S-K record each were analysed. 115,826 patient (3.86%) experienced hyperkalaemia (S-K &amp;gt;5.0mmol/L), in which 28,254 patients (0.94%), experienced S-K ≥5.5mmol/L. In patients with chronic kidney disease, heart failure, hypertension, and diabetes mellitus, the proportions of patients who experienced hyperkalaemia were 22.89%, 12.54%, 7.11% and 6.51%, respectively. Composition proportion of who experienced S-K ≥ 5.5mmol/L, in the patients with CKD and HF, defined as the proportion of patients experienced S-K≥ 5.5mmol/L in all hyperkalaemia patients, were 39.27% and 32.16% respectively, higher than the general population (16.3%). Geographic analysis showed that provinces with higher proportions of hyperkalaemia were Jiangsu (9.22%), Hebei (8.31%), Tianjin (6.74%), Hunan (6.27%) and Liaoning (5.56%). In addition, the seasonal proportion varied as winter (4.18%), autumn (3.93%), spring (3.83%) and summer (3.57%). In patients with hyperkalaemia, the overall hyperkalaemia diagnosed rate within the episode was 2.53%. Diagnosed rates increased by the severity of hyperkalaemia, patients with S-K ≥7.0 mmol/L showed the highest diagnosed rate of 9.63%. The overall hyperkalaemia treated rate was 8.69%. The treated rate of patients with S-K 5.0 to 5.5mmol/L was much lower than that of patients with S-K 5.5 -6.0mmol/L (6.6% vs. 12.01%). The overall retesting rate within 7 days was 11.41%. Patients with S-K 5.0-5.5 mmol/L were retested less frequently (8.51%) than those with S-K ≥5.5 mmol/L (15.56-21.76%). Conclusion The proportions of hyperkalaemia in patients with chronic kidney disease, heart failure, hypertension and diabetes were higher than the proportion in overall outpatients. The severity of hyperkalaemia increased in patients with chronic kidney disease and heart failure. The diagnosed rate, treated rate and resting rate of hyperkalaemia in outpatients were low, showing a slight raise with increased severity.

Sex differences in mineralocorticoid receptor antagonist trials: a pooled analysis of three large clinical trials.

Women with heart failure (HF) are under-represented in individual randomized clinical trials (RCTs). Little is known about sex-specific treatment effects in HF medications. We evaluated sex differences in the response to mineralocorticoid receptor antagonists (MRAs) in major HF MRA trials, including a broad spectrum of left ventricular ejection fraction (LVEF). Individual patient data fixed-effect meta-analysis was performed using 6167 patients (31.4% were women) recruited in three placebo-controlled RCTs: Randomized Aldactone Evaluation Study (RALES), Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) and Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT)-Americas. Compared to men, women were older, had higher body mass index and lower glomerular filtration rate. They also had higher LVEF and poorer New York Heart Association functional class and were less likely to be taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Placebo-arm event rates were lower for women compared with men (15.4 vs. 22.1 per 100 person-year; P=0.002). MRAs reduced consistently, in men and women, the relative risk for cardiovascular death or HF hospitalization (P for interaction=0.83), cardiovascular death (P for interaction=0.44) and all-cause death (P for interaction=0.19). These findings remained consistent after adjustment for potential confounders, regardless of LVEF. There was no sex-specific impact of MRA on the rate of hyperkalaemia and worsening renal function during the median 22 months of follow-up. In three large MRA RCTs, women were substantially different from men with regard to their clinical features and event rates. Nonetheless, this meta-analysis supports a consistent and beneficial MRA effect regardless of sex.

Prevalence, Length of Stay, and Hospitalization of Acute Kidney Injury in Patients With and Without Sjogren's Syndrome.

Background:Literature on the outcome of acute kidney injury (AKI) in Sjogren’s syndrome (SJS) is quite scanty. Acute kidney injury has emerged as a significant cause of morbidity and mortality in patients with autoimmune diseases such as systemic lupus erythematosus.Objective:To examine the outcome of AKI with and without SJS. To achieve this, we examined the prevalence, mortality, outcomes, length of stay (LOS), and hospital charges in patients with AKI with SJS compared with patients without SJS from a National Inpatient Sample (NIS) database in the period 2010 to 2013.Design:A retrospective cohort study using NIS.Setting:United States.Sample:Cohort of 97 055 weighted patient discharges with AKI from the NIS.Measurements:Not applicable.Methods:Data were retrieved from the NIS for adult patients admitted with a principal diagnosis of AKI between 2010 and 2013, using the respective International Classification of Diseases, Ninth Revision (ICD-9) codes. The study population divided into 2 groups, with and without Sjogren’s disease. Multivariate and linear regression analysis conducted to adjust for covariates. We omitted patients with systemic sclerosis and rheumatoid arthritis from the analysis to avoid any discrepancy as they were not meant to be a primary outcome in our study.Results:The study population represented 97 055 weighted patient discharges with AKI. Analysis revealed AKI patients with Sjogren’s compared with patients without Sjogren’s had statistically significant lower hyperkalemia rates (adjusted odds ratio: 0.65, confidence interval: 0.46-0.92; P = .017. There was no statistically significant difference in mortality, LOS, hospital charges, and other outcomes.Limitations:Study is not up to date as data are from ICD-9 which are testing data from 2010 to 2013, and data were obtained through SJS codes, which have their limitations. Also, limitations included lack of data on metabolic acidosis, hypokalemia, and not including all causes of AKI.Conclusions:At present, our study is unique as it has examined prevalence, mortality, and outcomes of Sjogren’s in patients with AKI. Patients with Sjogren’s had significantly lower hyperkalemia during the hospitalization. Further research is needed to identify the underlying protective mechanisms associated with Sjogren’s that resulted in lower hyperkalemia.Trial registration:Not applicable.