Incidence Of Hyperkalemia Research Articles

The LIFT trial: study protocol for a double-blind, randomised, placebo-controlled trial of K+-binder Lokelma for maximisation of RAAS inhibition in CKD patients with heart failure

BackgroundCKD is common in heart failure (HF) and associated with morbidity and mortality, yet life-prolonging medications such as renin-angiotensin-aldosterone inhibitors (RAASi) are underused due to risk of hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is a potassium-binding medication that has been shown to reduce incidence of hyperkalaemia in CKD, non-CKD, and HF populations, which we propose will support maximisation of RAASi therapy.MethodsWe propose a 1:1 randomised, double-blind, placebo-controlled trial in which participants will receive either SZC or placebo. We will up-titrate participants’ RAASi therapy while monitoring their serum potassium levels and adjusting their SZC dose if necessary. Participants with CKD and HF will be recruited from CKD and HF clinics at St George’s Hospital. The total study period will be 18 months; 130 participants will be enrolled for approximately two months each following screening. Our primary outcome will be the proportion of participants who achieve maximum RAASi dose while maintaining normokalaemia. Secondary outcomes include participants reaching maximum RAASi dose without severe hyperkalaemia; time from randomisation to hyperkalaemia; time from randomisation to severe hyperkalaemia; number of RAASi dose escalations per participant; final doses of RAASi therapy; changes in quality of life score, eGFR, ACR, serum sodium, troponin T; number and duration of hospital admissions; and within-participant change in serum potassium compared to baseline.DiscussionThis trial will be the first to examine the use of SZC for the maximisation of RAASi dosing in patients with advanced CKD and HF. We will assess the impact of achieving target RAASi dosing on hospital admission rates and duration of stay, with the hope that optimum RAASi treatment will translate into reduced morbidity and improved QoL. If clinical benefit is demonstrated, we hope that the joint multidisciplinary CKD-HF approach will be expanded.Trial registrationEudraCT number 2020–002946-18. Registered on 08 June 2020. Online record pending.

819-P: Comparison of Two Nurse-Driven Adult Diabetic Ketoacidosis (DKA) Treatment Protocols Using a Single Bag vs. Simultaneous Two-Bag Maintenance Intravenous Fluids

Objective: Evaluate safety and efficacy of a novel, simultaneous 2-bag (2B) maintenance intravenous fluid (IVF) DKA protocol compared with a conventional, single 1-bag (1B) protocol in adults. Methods: Retrospective, observational review of patients treated with a DKA protocol from March-June 2017 (1B group) and March-June 2019 (2B group). One bag (1B) protocol: individual infusion of 1B IVF of ½ NS, ½ NS + KCL, D5W, OR D5W + KCL. Two bag (2B) protocol: simultaneous IVF infusion of 2B of D10W + KCL AND ½ NS + KCL. Safety endpoints of hypoglycemia, hyperkalemia, hypokalemia as well as efficacy endpoints of DKA resolution, incidence of rebound hyperglycemia, and hospital length of stay (LOS) were evaluated. Results: A total of 605 patients were included (1B: n=204; 2B: n=401). Both groups had similar baseline characteristics except a higher baseline beta-hydroxybutyrate level in the 2B group than 1B (3.2 vs. 2.4; P=0.02) and differences in distribution of Body Mass Index (BMI) categories. Safety: Significantly fewer patients had hypoglycemia (BG <70 mg/dL) in the 2B group than 1B (15% vs. 22%, P=0.04), but severe hypoglycemia (BG < 40 mg/dL) was not different (0.5% vs. 1.5%, P=0.3). Incidence of hyperkalemia (K > 5.2 mEq/L) was significantly lower in the 2B group than 1B (10% vs. 21%, P<0.01), but hypokalemia (K < 3.3 mEq/L) was not different (21% vs. 24%, P=0.4). Efficacy: Median time to DKA resolution was similar between the 2B and 1B (15.0 vs. 15.6 hours, P=0.6). Rebound hyperglycemia (BG > 250 mg/dL) was less in 2B than 1B (29% vs. 44%, P<0.01). The 2B group had a trend of decreased LOS, but the difference was not statically significant (3.7 vs. 4.3 days, P=0.06). Conclusion: In adult patients with DKA, a 2-bag protocol performed better in hypoglycemia, hyperkalemia, and rebound hyperglycemia without changing time to DKA resolution or LOS. In addition, the 2-bag protocol offered simplicity by decreasing the number of IVF bag options for the nurse. Disclosure R. Halfon: Stock/Shareholder; Spouse/Partner; Pfizer Inc. D. Dreucean: None. M. Sirimaturos: None. A. R. Sadhu: None.

MO727EFFECT OF SACUBITRIL/VALSARTAN ON SERUM POTASSIUM AND BLOOD PRESSURE LEVELS OF DIALYSIS PATIENTS WITH HEART FAILURE

Abstract Background and Aims Heart failure is a frequent complication in patients with chronic kidney disease (CKD). As the kidney function declines, the incidence of heart failure and all-cause mortality increases. Heart failure is treated based on the ejection fraction and most of the treatments are often dependent on the renal function. The treatment guidelines of heart failure are not entirely applicable to those with CKD, since this population is usually not included in the randomized control trials. The introduction of neprilysin-inhibitor changed the paradigm of heart failure with reduced ejection fraction (HFrEF) treatment but the effects on dialysis patients is still under studied. Sacubitril/Valsartan is an ARNI that has been recommended as a treatment for symptomatic HFrEF. Monitoring of renal function and potassium is recommended for patients who will take Sacubitril/Valsartan and the two most common side effects are hyperkalemia and hypotension. This study evaluated the safety of Sacubitril/Valsartan by assessing the incidence of hyperkalemia and hypotension on patients undergoing maintenance dialysis - peritoneal or hemodialysis. The objective of the study was to compare the effect of losartan against sacubitril/valsartan on the systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum potassium level across three time points (1st, 2nd, and 3rd month follow-up). Method This retrospective, cohort, single-center study of dialysis patients with HFrEF is designed to assess the safety of Sacubitril/Valsartan versus Losartan based on the blood pressure and serum potassium level. A total of 96 patients on dialysis diagnosed with HFrEF was included in the study. Half was prescribed with Sacubitril/Valsartan while half was prescribed with Losartan. Serum potassium, systolic and diastolic blood pressure were recorded at baseline and monthly on the first three months of follow-up. Baseline 2d echocardiography was also reviewed. Results There were 96 chronic kidney disease patients with HF; 48 were on peritoneal dialysis and 48 on hemodialysis. Per group, 24 were given Losartan and 24 were given Sacubitril/Valsartan for 3 months. The mean age was 47.5 (15.5) years and ranges from 19 to 78 years old. Sixty two percent were males. The most common diagnosis were glomerulonephritis (36.5%), hypertensive nephrosclerosis (27.1%) and diabetic nephropathy (26%). In this retrospective study, we found that there were no episodes of hypotension and hyperkalemia on both hemodialysis and peritoneal dialysis patients who were prescribed with Sacubitril/Valsartan. All the hemodialysis patients included in this study were maintained on thrice a week hemodialysis sessions and the peritoneal dialysis patients had at least 3 exchanges per day. There were no significant change at three points in time (1st, 2nd, and 3rd month follow-up) in the levels of systolic blood pressure (p-value= 0.780, 0.609, 0.926), diastolic blood pressure (p-value= 0.692, 0.206, 0.527), and serum potassium (p-value= 0.212, 0.084, 0.095) on patients maintained on Sacubitril/Valsartan compared to Losartan. There was no evidence of hyperkalemia or hypotension on dialysis patients taking both medications. Conclusion Sacubitril/Valsartan is recommended in the therapy for HFrEF because of the documented benefits in the non-CKD and non-dialysis CKD patients. In this study, Sacubitril/Valsartan is well tolerated and has same effect on the serum potassium and blood pressure compared to Losartan. We concluded that there was no episode of hyperkalemia and hypotension on dialysis patients taking both medications. For the first time, this study demonstrated that Sacubitril/Valsartan is safe to be used in dialysis patients.

Safety and Efficacy of Perioperative Sublingual Tacrolimus in Pancreas Transplant Compared With Oral Tacrolimus.

Early posttransplant, the administration of oral or enteral medications in pancreas transplant is challenging because of the management of postoperative ileus and gastroparesis. The use of sublingual tacrolimus may offer a promising alternative. The objective of this study was to compare the pharmacokinetics and perioperative outcomes between oral and sublingual tacrolimus in pancreas transplant. This was a single-center, retrospective study of pancreas transplants between January 1, 2011, and July 1, 2018. We transitioned our tacrolimus protocol from oral to sublingual dosing in pancreas transplant patients beginning January 1, 2017. This analysis included 54 pancreas transplant recipients, with 17 patients on sublingual tacrolimus matched to 37 patients on oral tacrolimus. Within the sublingual group, it took a mean of 3.2 days to achieve a therapeutic tacrolimus trough level (≥8 ng/mL) compared with a mean of 3.8 days in the oral group (P = .175). There was no difference in the incidence of hyperkalemia and supratherapeutic tacrolimus levels between groups. The conversion factor from sublingual to oral in this patient population was 0.67, which was different than what has been reported in other populations. Clinical outcomes were similar between groups. Sublingual tacrolimus use in pancreas transplant patients appears to be a safe and effective strategy to avoid oral or intravenous therapy in the perioperative period and may reduce the time to achieve therapeutic levels.

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).

Safety of a Nurse-Driven Standardized Potassium Replacement Protocol in Critically Ill Patients With Renal Insufficiency.

In critically ill patients, maintaining appropriate serum potassium concentrations requires careful supplementation to correct hypokalemia but avoid hyperkalemia. At the study institution, an institution-based, nurse-driven standardized electrolyte replacement protocol is used in critically ill patients with a serum creatinine concentration of 2 mg/dL or less. If the serum creatinine concentration is greater than 2 mg/dL, electrolyte replacement requires a physician order. To determine if standardized potassium supplementation is safe in critically ill patients with renal insufficiency not requiring renal replacement therapy. This study was an institutional review board-approved, single-center, retrospective evaluation of critically ill patients receiving intravenous potassium replacement per protocol. Patients were grouped according to serum creatinine concentration (≤ 2 mg/dL or > 2 mg/dL) at the time of replacement. The primary outcome was the incidence of hyperkalemia (potassium concentration ≥ 5 mEq/L) following potassium replacement. Secondary outcomes were the incidence of hyperkalemia, change in serum potassium concentration, and need for hyperkalemia treatment. Outcomes were analyzed using χ2 and t tests. Of 814 patients screened, 145 were included (99 with serum creatinine ≤ 2 mg/dL and 46 with serum creatinine > 2 mg/dL). The incidence of hyperkalemia was not different between groups (P = .57). Five patients experienced hyperkalemia; none received hyperkalemia treatment. Change in serum potassium was similar for patients in the 2 groups (P = .33). A standardized, nurse-driven electrolyte replacement protocol can be used safely in critically ill patients with renal insufficiency not requiring renal replacement therapy.

Incidence of hyperkalemia during hypertonic saline test for the diagnosis of diabetes insipidus.

ObjectiveHyperkalemia has been reported upon different hypertonic saline infusion protocols. Since hypertonic saline test has recently been validated for the differential diagnosis of diabetes insipidus (DI), we aimed to investigate the course of plasma potassium during the test.DesignWe analyzed data of 90 healthy volunteers and 141 patients with polyuria–polydipsia syndrome (PPS) from two prospective studies evaluating the hypertonic saline test. Our primary outcome was the incidence rate of hypertonic saline-induced hyperkalemia > 5 mmol/L.MethodsParticipants received a 250 mL bolus of 3% NaCl solution, followed by 0.15 mL/min/kg body weight continuously infused targeting a plasma sodium level of 150 mmol/L. Blood samples and clinical data were collected every 30 min.ResultsOf the 231 participants, 16% (n = 37/231) developed hyperkalemia. The incidence of hyperkalemia was higher in healthy volunteers and in patients with primary polydipsia (25.6% (n = 23/90) and 9.9% (n = 14/141), respectively), and only occurred in 3.4% (n = 2/59) of patients with diabetes insipidus. Hyperkalemia developed mostly at or after 90-min test duration (81.1%, n => 30/37). Predictors of hyperkalemia (OR (95% CI)) were male sex (2.9 (1.2–7.4), P => 0.02), a plasma potassium at baseline > 3.9 mmol/L (5.2 (1.8–17.3), P => 0.004), normonatremia at 30-min test duration (3.2 (1.2–9.5), P => 0.03), and an increase in potassium levels already at 30-min test duration as compared to baseline (4.5 (1.7–12.3), P => 0.003). Hyperkalemia was transient and resolved spontaneously in all cases.ConclusionThe hypertonic saline test can lead to hyperkalemia, especially in patients with primary polydipsia who experience a longer test duration. Monitoring potassium levels in these patients is recommended.

Consenso sobre el manejo de la hiperpotasemia en pacientes con insuficiencia cardíaca: recomendaciones de la SEC-SEMI

Use of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with heart failure (HF) and reduced ejection fraction is associated with functional improvement, an increase in perceived quality of life, a reduction in the probability of cardiovascular death, and a decrease in the number of hospitalizations. Some of these drugs are also efficacious in patients with chronic kidney disease and albuminuria as well as in patients with resistant hypertension. Despite their numerous benefits, RAASi are associated with an increase in incidence of hyperkalemia, especially in patients with concomitant chronic kidney disease. Hyperkalemia is a common electrolyte disorder that is defined as an elevation in plasma concentrations of potassium above 5 mEq/L. It has been related to rehospitalizations, malignant arrhythmias, and an increase in mortality. On the other hand, optimized treatment with RAASi requires progressive dose increases which can in turn entail a greater probability of hyperkalemia. For all of these reasons, it is necessary to establish management and treatment guidelines for these patients. This consensus document arises from this objective. Its recommendations have been developed by a group of ten experts and reviewed by a panel of another ten specialists in the treatment of patients with HF (ten cardiologists and ten internists in total). This document has been endorsed by the Spanish Society of Cardiology (SEC, for its initials in Spanish) and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish).

Epidemiology of hyperkalemia in CKD patients under nephrological care: a longitudinal study.

Hyperkalemia is a potential life-threatening condition among chronic kidney disease (CKD) patients. Available estimates of the burden of this alteration in CKD are mainly derived from large administrative databases. Since K measurements in patients in these databases are often dictated by clinical reasons, longitudinal studies including pre-planned measurements of potassium independently of clinical complication/symptoms may produce more reliable estimates of the frequency and the risk factors underlying hyperkalemia in CKD patients. We estimated the prevalence and the incidence of hyperkalemia in a longitudinal study in 752 stages 2-5 CKD patients lasting 3years and including up to seven pre-planned assessment of key biochemical measurements including K. At baseline, 203 out of 752 patients (27%) had serum K > 5.0mM/L and 33% had acidosis (HCO3 ≤ 22mmol/L). Among those without hyperkalemia at baseline (n = 549), 284 patients developed this alteration across the 3-year follow-up. The point prevalence of hyperkalemia rose from 27% (baseline) to 30% (last visit) (P = 0.001). In a multivariate model, hyperkalemia at baseline [odds ratio (OR):7.29, 95% CI 5.65-9.41, P < 0.001], venous bicarbonate levels [OR (1mmol/l): 0.92, 0.89-0.96, P < 0.001], eGFR [OR (1ml/min/1.73m2): 0.98, 0.97-0.99, P < 0.001], use of ACE inhibitors (OR: 1.68, 1.28-2.19, P < 0.001) and angiotensin II antagonists (OR: 1.30, 1.01-1.68, P = 0.045) were related to hyperkalemia over time. Of note, venous bicarbonate levels emerged as an independent risk factor of hyperkalemia over time also in a separate analysis of patients with and without hyperkalemia at baseline. In a cohort of CKD patients including pre-planned measurements of K, 27% of patients had hyperkalemia. Metabolic acidosis and the use of drugs interfering with renin-angiotensin system were the strongest modifiable risk factors for this potentially life-threatening alteration in CKD in longitudinal analyses in the whole study cohort and in patients developing de novo hyperkalemia over time.

Incidence of Co-Trimoxazole-Induced Hyperkalemia in a Tertiary Care Hospital.

BackgroundCo-trimoxazole is a broad-spectrum antibiotic associated with hyperkalemia.ObjectiveTo determine the incidence of hyperkalemia and its risk factors in patients receiving co-trimoxazole.Materials and MethodsA retrospective observational study involving all patients who received co-trimoxazole between 1 January 2012 and 1 January 2013 was conducted. Subjects were identified through a list generated from a computerized pharmacy system. The patients’ demographic and clinical characteristics were retrieved from electronic medical records. Data were analyzed using univariate and multivariate logistic regression.ResultsOne hundred sixty-one patients fulfilled the eligibility criteria. Of these, 46 (28.6%) experienced hyperkalemia. Around 35 (76%) of the patients who experienced hyperkalemia received co-administered medications that might induce hyperkalemia. The co-administration of co-trimoxazole with other medications that may induce hyperkalemia was found to be associated with higher incidence of hyperkalemia when compared to co-trimoxazole administration alone [adjusted OR 3.2, 95% CI (1.4–7.3), p=0.005]. Additionally, age > 60 years was associated with an increased risk of hyperkalemia when compared to younger age group 18–39 years [adjusted OR 6.5, 95% CI (2.1–19.7); p=0.001].ConclusionCo-trimoxazole use is associated with high incidence of hyperkalemia, especially among older patients and those receiving it in combination with other medications that might contribute to hyperkalemia development such as calcineurin inhibitors and β-blockers.

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.

Evaluation of the safety and tolerability of spironolactone in patients with heart failure and chronic kidney disease.

Spironolactone reduces morbidity and mortality in patients with heart failure (HF) with reduced ejection fraction (EF) and decreases hospitalizations in HF with preserved EF. To minimize the risk of hyperkalemia, patients must have an estimated glomerular filtration rate (eGFR) > 30mL/min/1.73m2 and potassium < 5.0mEq/L prior to initiation; however, spironolactone is prescribed outside these parameters. The objective of this study was to evaluate the safety and tolerability of spironolactone in patients with HF and chronic kidney disease (CKD). This single-center, retrospective cohort study evaluated patients ≥ 18years with HF and CKD stages 3-5 who received ≥ 48h of spironolactone therapy and were hospitalized from February 2018 to August 2019. The primary outcome was incidence of hyperkalemia (potassium ≥ 5.5mEq/L). Overall, 121 patients were evaluated: 52.1% (n = 63) had an EF > 40% and 47.9% (n = 58) had an EF ≤ 40% with 69.4% (n = 84) CKD stage 3, 24.8% (n = 30) stage 4, and 5.8% (n = 7) stage 5. Spironolactone was initiated prior to admission (PTA) for 54.5% (n = 66) of patients, while 45.5% (n = 55) of orders were initiated during hospitalization. Eight patients (6.6%) experienced inpatient hyperkalemia-all with PTA spironolactone. Patients who experienced inpatient hyperkalemia had a numerically lower eGFR that was not statistically significant (35.40 vs. 38.22mL/min/1.73m2; p = 0.730). Patients with CKD stage 3 (n = 4) had numerically higher rates of inpatient hyperkalemia than stages 4 (n = 1) or 5 (n = 3) (50%, 12.5%, and 37.5% respectively; p < 0.05). Spironolactone may be safe to initiate in hospitalized patients with HF and CKD; however, appropriateness of therapy must be assessed upon admission to the hospital. Larger studies are needed for conclusive results.

Clinical Analysis of Electrolyte Disorders in Patients with Diabetic Ketoacidosis.

The changes in the electrolyte profiles in patients with diabetic ketoacidosis (DKA) have rarely been reported. This study reports the abnormalities in the electrolyte profile, such as serum potassium, sodium, chloride, calcium, magnesium, and phosphorus. Forty individuals in each of the DKA, diabetic ketosis (DK), nonketotic diabetes mellitus, and healthy control groups were included in this study to evaluate their clinical indicators, such as blood glucose, glycated hemoglobin (HbA1c), renal function, electrolytes, and arterial blood gas concentrations. Compared with the other three groups, patients in the DKA group had a longer course of diabetes; significantly higher levels of blood glucose, HbA1c, and serum creatinine (p < 0.05 or p < 0.001); lower estimated glomerular filtration rate (eGFR) (p < 0.001); and higher levels of serum potassium, sodium, phosphorus, magnesium, and effective osmotic pressure (p < 0.05). In the DKA patients, the incidences of hyperkalemia and hypokalemia were 32.5% (p < 0.05 or p < 0.001 vs. the other groups) and 7.5%, respectively. In the DKA patients, type 1 diabetes patients were younger and had higher blood glucose than type 2 patients (p < 0.05), but the electrolyte profiles were not significantly different. There were no significant differences in the serum electrolyte profile between mild to moderate DKA patients and severe DKA patients. Serum potassium was negatively correlated with eGFR (r = -0.378, p = 0.018). Regression analysis showed that eGFR was an important factor affecting serum potassium (β = -0.378, p = 0.018). When DKA occurs in diabetes patients, the renal function deteriorates significantly because the electrolytes are generally elevated due to hemoconcentration. Hyperkalemia is the main manifestation, and it is necessary to prevent the decrease in serum potassium during the treatment.

Initial and Recurrent Hyperkalemia Events in Patients With CKD in Older Adults: A Population-Based Cohort Study.

Background:The risk of hyperkalemia is elevated in chronic kidney disease (CKD); however, the initial and recurrent risk among older individuals is less clear.Objectives:We set out to examine the initial and 1-year recurrent risk of hyperkalemia by level of kidney function (estimated glomerular filtration rate, eGFR) in older adults (≥66 years old).Design:Population-based, retrospective cohort studySettings:Ontario, CanadaParticipants:905 167 individuals (≥66 years old) from 2008 to 2015.Measurements:Serum potassium valuesMethods:Individuals were stratified by eGFR (≥90, 60-89, 30-59, 15-29 mL/min/1.73 m2) and examined for the risk of incident hyperkalemia (K ≥ 5.5 mEq/L) using adjusted Cox proportional hazards models. The 1-year risk of recurrent hyperkalemia was examined using multivariable Andersen-Gill models.Results:Among a population of 905 167 individuals (15% eGFR ≥ 90, 58% eGFR 60-89, 25% eGFR 30-59, 3% eGFR 15-29) with a potassium measurement, there were a total of 18 979 (2.1%) individuals with hyperkalemia identified. The event rate (per 1000 person-years) and adjusted hazard ratio (HR) of hyperkalemia was inversely associated with eGFR (mL/min; eGFR >90 mL/min: 8.8, referent, 60-89 mL/min: 11.8 HR 1.41; eGFR 30-59: 39.8, HR 4.37; eGFR 15-29: 133.6, 13.65) and with an increasing urine albumin-to-creatinine ratio (ACR, mg/mmol; ACR< 3: 14, referent, ACR 3-30: 35.1, HR 1.98; ACR >30: 93.7, 4.71). The 1-year event rate and adjusted risk of recurrent hyperkalemia was similarly inversely associated with eGFR (eGFR ≥ 90: 10.1, referent, eGFR 60-89: 14.4, HR 1.47; eGFR 30-59: 54.8, HR 4.90; eGFR 15-29: 208.0, HR 12.98). Among individuals with a baseline eGFR of 30 to 59 and 15 to 29, 0.9 and 3.8% had greater than 2 hyperkalemia events. The relative risk of initial and recurrent hyperkalemia was marginally higher with RAAS blockade. Roughly 1 in 4 individuals with hyperkalemia required hospitalization the day of or within 30 days after their hyperkalemia event.Limitations:Limited to individuals aged 66 years and above.Conclusions:Patients with low eGFR are at a high risk of initial and recurrent hyperkalemia.Trial registration: N/A

A Model to Predict Risk of Hyperkalemia in Patients with Chronic Kidney Disease Using a Large Administrative Claims Database.

BackgroundChronic kidney disease (CKD) is responsible for substantial clinical and economic burden. Drugs that inhibit the renin-angiotensin-aldosterone system inhibitors (RAASi) slow CKD progression in many common clinical scenarios. Guideline-directed medical therapy requires maximal recommended doses of RAASi, which clinicians are often reluctant to prescribe because of the associated risk of hyperkalemia (HK).ObjectiveThis study aims to develop and validate a model to identify individuals with CKD at elevated risk for developing HK over a 12-month period on the basis of lab, medical, and pharmacy claims.MethodsUsing claims from a large US healthcare payer, we developed a model to predict the probability of individuals identified with CKD but not HK in 2016 (baseline year [BY]) who developed HK in 2017 (prediction year [PY]). The study population was comprised of members continuously enrolled with medical and pharmacy benefits and CKD (BY). Members were excluded from the analysis if they had HK (by lab results or diagnosis code) or dialysis (BY). Prediction model performance measures included area under the receiver operating characteristic curve (AUROC), calibration, and gain and lift charts.ResultsOf 435,512 members identified with CKD but not HK (BY), 6235 (1.43%) showed incident HK (PY). Compared with individuals without incident HK (PY), these members had a higher comorbidity burden, use of RAASi, and healthcare utilization. The AUROC and calibration analyses showed good predictive accuracy (area under the curve [AUC]=0.843 and calibration). The top 2 HK-prediction deciles identified 75.94% of members who went on to develop HK (PY).ConclusionGuideline-recommended doses of RAASi therapy can be limited by the risk of HK. Novel potassium binders may permit more patients at risk to benefit from these maximal RAASi doses. This predictive model successfully identified the risk of developing HK up to 1 year in advance.

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.

Serum potassium as a predictor of adverse clinical outcomes in patients with increasing comorbidity burden.

AimsThe aim of this study was to establish whether patients with multiple comorbidities may be at elevated risk of hyperkalaemia (HK), a potentially life-threatening electrolyte imbalance, and the associated adverse clinical outcomes.Methods and resultsThis was a retrospective, observational cohort study using UK primary and secondary care data. Adult patients with at least one of: resistant hypertension, chronic kidney disease stage 3+, dialysis, heart failure (HF), and diabetes, were eligible for inclusion. According to their diagnoses, patients were grouped into overlapping cohorts that were updated as multimorbidity progressed. Outcomes of interest were incident HK, all-cause mortality (ACM), and major adverse cardiovascular events (MACE). A total of 673 686 patients met the eligibility criteria, 36.3% of whom developed multimorbidity during the study period. A consistent U-shaped association was observed between serum K+ level and adjusted incidence of ACM and MACE. Hyperkalaemia was progressively more common with increasing Charlson Comorbidity Index (CCI). Relative to a CCI <3, scores of ≥3 to <6, and ≥6 were associated with 2.9- and 6.2-fold increases, respectively, in crude HK (serum K+ ≥5.0 mmol/L) incidence rate. In all condition-based cohorts except for HF, there was a clear correlation between increasing CCI and the risk of ACM and MACE associated with hypokalaemia and HK.ConclusionPatients with a higher CCI are at an increased risk of developing HK and appear more prone to adverse clinical outcomes associated with abnormal serum K+ levels, warranting additional routine clinical monitoring.

Tolerability and Effect of Angiotensin Receptor Neprilysin Inhibitors in Adult Congenital Patients with Systemic Right Ventricle

Introduction Adult Congenital Heart Disease (ACHD) patients have an increased mortality and morbidity from heart failure. Angiotensin Receptor-Neprilysin Inhibitors (ARNI) have emerged as a standard of therapy for adults with heart failure. However, the effects of these medicines have not been studied in ACHD patients. Hypothesis ARNI's are well tolerated and have beneficial cardiovascular effects in ACHD patients. Method Twenty-one ACHD patients with systemic right ventricle were prescribed ARNI at our institution. Demographics, vital signs, laboratory results, functional status, imaging data, and outcomes were collected by retrospective electronic review. Statistical analysis was performed using paired t test. Results Twenty-one patients with systemic right ventricle were treated with ARNI: 16 D-Transposition of great arteries (TGA) with atrial switch, 1 congenitally corrected TGA, and 1 Taussig Bing transposition type and atrial switch. Fifteen (71.4%) were male, mean age 39.8±6.5 years. Baseline RVEF was 33.4+/-8.6%. Baseline peak VO2 was 18.1+/-4.3 mL/min/kg. By functional status, 10 were in NYHA class II (50%), 7 in class III (35%), and 2 in class IV (one unknown). Median follow-up was 14.1 (9.4-27.8) months. All patients tolerated Entresto for at least six months. High dose Entresto was achieved in 4 (19%) patients, 3 (14.3%) were on moderate dose, and 14 (66.7%) were on low dose. Only 2 (9.5%) patients discontinued Entresto after 9 and 11 months due to hypotension. There was no significant change in creatinine (0.8±0.4 mg/dL versus 1.0±0.3 mg/dL, p=NS), no incidence of hyperkalemia, angioedema, or major side effect including death. Systolic blood pressure was 118.2+/-14.2 mmHg at baseline and decreased with ARNI use (112.4+/-16.4 mmHg at 0-3 months, 112.4+/-12.8mmHg at 3-6 months and 108.5+/-10.3mmHg at 6-12 months, p values by paired t test 0.02, NS, and NS respectively). Corresponding values for diastolic blood pressure were 74.5+/-9.6mmHg (baseline), 72.4+/-14.3mmHg, 62.8+/-10.1 and 70.45+/-10.9mmHg (p values by paired t test NS, 0.009, and NS respectively). Mean NYHA class improved from 2.65+/-0.74 to 2.21+/-0.71 (p=0.008 by paired t-test). 5/12 (42%) of patients had an improvement in peak oxygen consumption on cardiopulmonary stress test, though this was not statistically significant. (16.8+/-4.8 mL/kg/min versus baseline 18.1+/-4.3 mL/min/kg, p=NS). Conclusion ARNI's are safe and well tolerated in ACHD patients. It is associated with mild decrease in blood pressure and improvement in functional class. The study findings are promising and highlight the need for larger, prospective, multicenter studies.

Effect of high-dose mineralocorticoid receptor antagonist eplerenone on urinary albumin excretion in patients with type 2 diabetes and high cardiovascular risk: Data from the MIRAD trial

AimAs mineralocorticoid receptor antagonists (MRAs) may possess renoprotective effects in type 2 diabetes (T2D), it was decided to investigate the impact of high-dose MRA on prespecified secondary endpoints—namely, change in urinary albumin–creatinine ratio (UACR) and 24-h ambulatory blood pressure—in the MIRAD trial. MethodsThis was a double-blind clinical trial in which T2D patients at high risk of or with established cardiovascular disease (CVD) were randomized to either high-dose (100–200 mg) eplerenone or a dose-matched placebo as an add-on to background antihypertensive treatment for 26 weeks. Safety was evaluated by the incidence of hyperkalaemia and kidney-related adverse events. ResultsA total of 140 patients were enrolled (70 in each group). Baseline UACR was 17 mg/g (geometric mean; 95% CI: 13–22); this decreased by 34% in the eplerenone group compared with the placebo group at week 26 (95% CI: −51% to −12%; P = 0.005). There was no significant decrease in 24-h systolic blood pressure (SBP) due to treatment (−3 mmHg; 95% CI: −6 to 1; P = 0.150). However, the observed change in 24-h SBP correlated with the relative change in UACR in the eplerenone group (r = 0.568, P < 0.001). Mean baseline (± SD) estimated glomerular filtration rate (eGFR) was 85 (± 18.6) mL/min/1.73 m2, and 12 (± 9%) had an eGFR of 41–59 mL/min/1.73 m2. No significant differences in the incidence of mild hyperkalaemia (≥ 5.5 mmol/L; eplerenone vs placebo: 6 vs 2, respectively; P = 0.276) and no severe hyperkalaemia (≥ 6.0 mmol/L) were observed. ConclusionThe addition of high-dose eplerenone to T2D patients at high risk of CVD can markedly reduce UACR with an acceptable safety profile.

The Association of Renin-Angiotensin-Aldosterone System Inhibitors With Outcomes Among a Predominantly Ethnic Minority Patient Population Hospitalized With COVID-19: The Bronx Experience.

Background and objectiveAngiotensin-converting enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) are commonly used for the treatment of patients with heart disease, hypertension (HTN), and diabetes mellitus (DM). In the aftermath of the emergence of the coronavirus disease 2019 (COVID-19) pandemic, initial data raised concerns that ACE/ARB use can increase the expression of ACE2 receptors, leading to the worsening of COVID-19. However, recent studies have suggested that their use might be safe in a select subgroup of patients. We conducted a single-center retrospective study to evaluate the association of in-patient use of ACE/ARB with outcomes among a predominantly ethnic minority patient population of the inner New York City (NYC).MethodsThis was a retrospective analysis of all hospital admissions with COVID-19 from March 1, 2020, to March 31, 2020.ResultsOf the 469 patients included in the study, 91 patients (19.4%) used ACE/ARB therapy during their hospital stay and were labeled as ACE/ARB group. Patients in the ACE/ARB therapy group were older and had a higher incidence of HTN, coronary artery disease (CAD), congestive heart failure, DM, asthma, and chronic obstructive pulmonary disease. Admission D-dimer, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels were similar between the two groups, but absolute lymphocyte count (ALC) was lower in the non-ACE/ARB group (0.971 k/ul vs. 1.135 k/ul, p=0.0144). The incidence of hyperkalemia and the rise in creatinine were similar between the two groups. Univariate analysis by treatment group using the log-rank test produced significant results (p=0.0062), indicating a higher survival rate for the ACE/ARB group.ConclusionThe use of ACE/ARB appears to be safe in all patients in whom their use is medically indicated.