Hyperkalemia In Patients Research Articles

The Cost Effectiveness of Patiromer for the Treatment of Hyperkalaemia in Patients with Chronic Kidney Disease with and without Heart Failure in Ireland.

Background and ObjectiveHyperkalaemia can be a life-threatening condition, particularly in patients with advanced chronic kidney disease with and without heart failure. Renin-angiotensin-aldosterone system inhibitor therapy offers cardiorenal protection in chronic kidney disease and heart failure; however, it may also cause hyperkalaemia subsequently resulting in down-titration or discontinuation of treatment. Hence, there is an unmet need for hyperkalaemia treatment in patients with chronic kidney disease with and without heart failure to enable renin-angiotensin-aldosterone system inhibitor use in this patient population. In this study, we develop a de novo disease progression and cost-effectiveness model to evaluate the clinical and economic outcomes associated with the use of patiromer for the treatment of hyperkalaemia in patients with chronic kidney disease with and without heart failure.MethodsA Markov model was developed using data from the OPAL-HK trial to assess the health economic impact of patiromer therapy in comparison to standard of care in controlling hyperkalaemia in patients with advanced chronic kidney disease with and without heart failure in the Irish setting. The model was designed to predict the natural history of chronic kidney disease and heart failure and quantify the costs and benefits associated with the use of patiromer for hyperkalaemia management over a lifetime horizon from a payer perspective.ResultsTreatment with patiromer was associated with an increase in discounted life-years (8.62 vs 8.37) and an increase in discounted quality-adjusted life-years (6.15 vs 5.95). Incremental discounted costs were predicted at €4979 per patient, with an incremental cost-effectiveness ratio of €25,719 per quality-adjusted life-year gained. Patients remained taking patiromer treatment for an average of 7.7 months, with treatment associated with reductions in the overall clinical event incidence and a delay in chronic kidney disease progression. Furthermore, patiromer was associated with lower overall rates of hospitalisation, major adverse cardiovascular events, dialysis, renin-angiotensin-aldosterone system inhibitor discontinuation episodes and renin-angiotensin-aldosterone system inhibitor down-titration episodes. At a willingness-to-pay threshold of €45,000 per quality-adjusted life-year in Ireland, treatment with patiromer was estimated to have a 100% chance of cost effectiveness compared with standard of care.ConclusionsThis study has demonstrated an economic case for the reimbursement of patiromer for the treatment of hyperkalaemia in patients with chronic kidney disease with and without heart failure in Ireland. Patiromer was estimated to improve life expectancy and quality-adjusted life expectancy, whilst incurring marginal additional costs when compared with current standard of care. Results are predominantly attributed to the ability of patiromer to enable the continuation of renin-angiotensin-aldosterone system inhibitor treatment whilst also reducing potassium levels.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-022-00357-z.

Management of hypertension in advanced kidney disease.

The aim of this study was to present recent developments in pharmacotherapy of hypertension in patients with advanced chronic kidney disease (CKD). In the AMBER trial, compared with placebo, the potassium-binder patiromer mitigated the risk of hyperkalaemia and enabled more patients with uncontrolled resistant hypertension and stage 3b/4 CKD to tolerate and continue spironolactone treatment; add-on therapy with spironolactone provoked a clinically meaningful reduction of 11-12 mmHg in unattended automated office SBP over 12 weeks of follow-up. In the BLOCK-CKD trial, the investigational nonsteroidal mineralocorticoid-receptor-antagonist (MRA) KBP-5074 lowered office SBP by 7-10 mmHg relative to placebo at 84 days with a minimal risk of hyperkalaemia in patients with advanced CKD and uncontrolled hypertension. The CLICK trial showed that the thiazide-like diuretic chlorthalidone provoked a placebo-subtracted reduction of 10.5 mmHg in 24-h ambulatory SBP at 12 weeks in patients with stage 4 CKD and poorly controlled hypertension. Enablement of more persistent spironolactone use with newer potassium-binding agents, the clinical development of novel nonsteroidal MRAs with a more favourable benefit-risk profile and the recently proven blood pressure lowering action of chlorthalidone are three therapeutic opportunities for more effective management of hypertension in high-risk patients with advanced CKD.

État des lieux sur l’hyperkaliémie chronique persistante en France : consensus d’experts par une approche Delphi

IntroductionIn France, no consensus document on the management of persistent hyperkalaemia is currently available. Variability in clinical practices has been observed. MethodsA consensus statement on the definition and the management of persistent hyperkalaemia was developed by a Delphi panel of French nephrologists between December 2019 (26 voting participants among 40 invited panellists in first round) and June 2020 (20 voting participants among 26 panellists in second round). ResultsPersisting hyperkalaemia not controlled with current treatment strategies may be defined as the occurrence of two or more hyperkalaemia episodes within a year despite the administration of cation-exchange resins or loop diuretics during the same year. Some patient characteristics (diabetes, chronic kidney disease from stage 3B to stage 5 without dialysis, chronic heart failure) are associated with an increased risk of developing persistent hyperkalaemia. There is a medical need for the management of persistent hyperkalaemia in patients treated with renin-angiotensin-aldosterone system inhibitors that is not met by current treatment strategies (including available cation-exchange resins). ConclusionsThe panel expressed a need for new treatment strategies validated by clinical trials.

Clinical and electrocardiogram presentations of patients with high serum potassium concentrations within emergency settings: a prospective study

BackgroundElevated potassium level is a common and reversible peri-arrest condition. Diagnosis and management of hyperkalemia in a short time is critical, where electrocardiogram (ECG) alterations might be helpful. We aimed to investigate the role of clinical features and ECGs in early diagnosing and treating hyperkalemia.MethodsProspectively, adult patients who presented to the emergency department (ED) from July 2019 to March 2020 with hyperkalemia (serum potassium ≥5.5mmol/L) were included. History was obtained, and laboratory investigations and ECGs were performed at the presentation and before initiating hyperkalemia therapy. Hyperkalemia severity was divided into mild (5.5–5.9mmol/L), moderate (6.0–6.4mmol/L), and severe (≥6.5mmol/L). A cardiologist and emergency physician blinded to laboratory values, study design, and patients’ diagnoses interpreted ECGs and presenting symptoms independently to predict hyperkalemia.ResultsSixty-seven hyperkalemic patients with a mean (±SD) serum potassium level of 6.5±0.7mmol/L were included in this study. The mean age was 63.9±15.1, and 58.2% were females. Hyperkalemia was mild in 10.4%, moderate in 40.3%, and severe in 49.3%. Almost two thirds of patients (71.6%) had hypertension, 67.2% diabetes, and 64.2% chronic kidney disease. About one-quarter of patients (22.4%) were asymptomatic, while fatigue (46.3%), dyspnea (28.4%), and nausea/vomiting (20.9%) were the most common presenting symptoms. Normal ECGs were observed in 25.4% of patients, while alterations in 74.6%. Atrial fibrillation (13.4%), peaked T wave (11.9%), widened QRS (11.9%), prolonged PR interval (10.5%), and flattening P wave (10.5%) were the most common. Peaked T wave was significantly more common in severe hyperkalemia (87.5%) than in mild and moderate hyperkalemia (12.5%, 0.0%, respectively) (p=0.041). The physicians’ sensitivities for predicting hyperkalemia were 35.8% and 28.4%, improved to 51.5% and 42.4%, respectively, when limiting the analyses to severe hyperkalemia. The mean (±SD) time to initial hyperkalemia treatment was 63.8±31.5 min. Potassium levels were positively correlated with PR interval (r=0.283, p=0.038), QRS duration (r=0.361, p=0.003), peaked T wave (r=0.242, p=0.041), and serum levels of creatinine (r=0.347, p=0.004), BUN (r=0.312, p=0.008), and CK (r=0.373, p=0.039).ConclusionsThe physicians’ abilities to predict hyperkalemia based on ECG and symptoms were poor. ECG could not be solely relied on, and serum potassium tests should be conducted for accurate diagnosis.

A cost-effectiveness analysis of patiromer for the treatment of hyperkalemia in chronic kidney disease patients with and without heart failure in Spain

Aims Renin-angiotensin-aldosterone system inhibitors (RAASi) therapy is commonly used to reduce the risk of death and to slow down disease progression in patients with chronic kidney disease (CKD), heart failure (HF) and hypertension. However, the cardio-renal benefits of RAASi therapy are also associated with an increased risk of hyperkalemia (HK), which may lead to dose reduction or discontinuation of therapy. Patiromer has demonstrated to reduce the risk of HK, which enables to maintain optimal doses of RAASi therapy. This study aimed to assess the cost-effectiveness of patiromer for the management of HK in CKD patients with and without HF in Spain. Methods A Markov model was developed to evaluate the costs and benefits of patiromer for the management of HK in patients with CKD stages 3–4 with and without HF treated with RAASi over a lifetime horizon. The main outcomes included total direct costs (€2021), quality-adjusted life-years (QALYs), life-years gained (LYG) and incremental cost-effectiveness ratio (ICER). Deterministic one-way and probabilistic sensitivity analyses were performed to assess the robustness of the results. Results Patiromer was more effective compared to no patiromer (5.76 vs 5.57 QALYs; 7.73 vs 7.50 LYG), and resulted in an incremental cost of €3,574, yielding an ICER of €19,092/QALY gained and of €15,236/LYG. Sensitivity analyses suggested that the results were robust to changes in most input parameters. Conclusions Patiromer is a cost-effective intervention in maintaining normokalemia and enabling optimal RAASi therapy in patients with CKD stages 3–4 with and without HF in Spain.

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim-sulfamethoxazole without changes in glomerular filtration rate.

Trimethoprim (TMP) inhibits the Na+ /K+ -ATPase present in the basement membrane of distal tubular epithelial cells. However, hyponatremia and hyperkalemia may develop in patients taking TMP-sulfamethoxazole (SMX). In addition, because TMP inhibits drug transporters, such as organic cation transporter 2 and multidrug and toxin extrusion protein 2-K in proximal tubules, reversible increases in the concentration of serum creatinine (SCr), the substrate of these transporters, may occur. Here, we investigated variability in SCr, serum sodium (Na+ ), and serum potassium (K+ ) concentrations after initiation of TMP-SMX treatment and evaluated the risk of hyponatremia and hyperkalemia in patients with increased SCr concentrations without changes in the glomerular filtration rate (GFR). In this retrospective study, all patients aged 20 years or older who received oral TMP-SMX during hospitalization were enrolled. The patients with estimated creatinine (Cr) clearance (eCCr) lower than 30 mL/min were excluded, as were patients taking drugs that were likely to induce renal dysfunction, drugs other than glucocorticoids that were likely to induce electrolyte imbalances, or drugs other than TMP that inhibit tubular Cr secretion. Additionally, those with SCr concentrations elevated more than 30% from baseline or serum blood urea nitrogen concentration levels above 20 mg/dL during follow-up were also excluded. In total, 111 patients were enrolled in the study. The common independent variable affecting the change rate in SCr, Na+ , and K+ concentrations (ΔSCr, ΔNa+ , and ΔK+ ) from baseline to the highest value during the follow-up period (14 days after initiation of TMP-SMX treatment) was the daily dose of TMP. There were significant correlations between ΔSCr and ΔNa+ or ΔK+ (ρ=-0.199, p=0.036 and ρ=0.244, p=0.010, respectively). Kaplan-Meier curves for hyponatremia and hyperkalemia with greater than or equal to grade 1 severity showed different profiles when the TMP dose varied (≤ 160 vs. > 160 mg/day; p=0.005 and 0.008). The cumulative incidences of both adverse effects were 64.7% (median: 7 days) and 29.4% in patients taking more than 160 mg/day TMP and 35.2% and 6.7% in patients taking 160 mg/day TMP or less. Thus, TMP may affect the kinetics of Cr, Na+ , and K+ in the proximal and distal tubules in a dose-dependent without changing the GFR. This study is the first report to demonstrate the degree of changes in SCr, Na+ , and K+ concentrations after initiation of TMP-SMX treatment. If SCr is elevated after initiation of TMP-SMX treatment, clinicians should be aware of decreased Na+ and increased K+ concentrations. TMP may increase the risks of hyponatremia and hyperkalemia in a dose-dependent manner without altering GFR.

MO879: Prevalence, Recurrence and Seasonal Variation of Hyperkalaemia in Patients Receiving Thrice-Weekly Haemodialysis

Abstract BACKGROUND AND AIMS Prospective cohort studies have shown that among patients on haemodialysis, hyperkalaemia is strongly associated with excess risk for cardiovascular-related hospitalizations and sudden cardiac death [1–4]. However, the actual burden of hyperkalaemia, the rates of its recurrence and seasonality in its variation still remain unclear. METHOD Between June 2020 and May 2021, 1786 mid-week predialysis serum potassium (sK) measurements were retrospectively recorded from 149 patients receiving thrice-weekly haemodialysis in a single-centre in Thessaloniki, Greece. The prevalence, recurrence and seasonal variation of hyperkalaemia were assessed using three prespecified sK thresholds (≥5.1, ≥5.5 and ≥ 6.0 mmol/L). RESULTS At baseline (June 2020), 60.4%, 42.2% and 13.4% of patients had sK levels ≥ 5.1, ≥5.5 and ≥ 6.0 mmol/L, respectively. At any time-point during the 1-year-long follow-up, 85.2%, 69.8% and 38.9% of patients experienced at least 1 hyperkalaemic episode at the sK threshold of ≥ 5.1, ≥5.5 and ≥ 6.0 mmol/L, respectively. Of the 104 patients experiencing an initial sK elevation ≥ 5.5 mmol/L, hyperkalaemia at the same threshold reoccurred in 60.6% at month-1, in 47.1% at month-2 and in 46.1% at month-3 of follow-up. Seasonal variation was also observed, with the prevalence of hyperkalaemia to be significantly higher in summer. In multivariate logistic regression analysis, shorter delivered haemodialysis < 4 h/session {odds ratio (OR): 2.568; [95% confidence interval (95% CI): 1.045–6.313]} and the use of a high versus a low K concentration in the dialysate (OR: 14.646; 95% CI: 2.727–78.647) were the two factors that were associated with a significantly higher odds of hyperkalaemia at any time-point of the follow-up period. CONCLUSION The present study shows that among patients receiving conventional thrice-weekly haemodialysis, the rates of hyperkalaemia prevalence and recurrence are very high, reflecting the large unmet need to identify more effective potassium-lowering therapeutic interventions in this high-risk population.

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.

Lactated Ringer's solution and risk of hyperkalemia in patients with reduced kidney function

BackgroundEmerging evidence supports the superiority of balanced crystalloids such as Lactated Ringer's (LR) compared to normal saline but concerns for the development of hyperkalemia have limited its use. Although LR inherently contains potassium, there exists a paucity of evidence to suggest that LR could potentiate hyperkalemia. To address this, we evaluated the effect of LR on serum potassium in patients with reduced kidney function who are at risk of developing hyperkalemia. MethodsWe conducted a single-center, retrospective cohort-based observational clinical study that included 293 clinical encounters who were hospitalized with an estimated glomerular filtration rate (eGFR) of < 30 ml/min/1.73m2, at the time of hospital admission. Subjects must have received a minimum of 500 ml of LR continuously during the admission. Only those with a minimum of one lab report within 24 hours prior to-, and post-LR administration that reported serum measurements of potassium, glucose, and bicarbonate levels were included. Other potential risk factors for developing hyperkalemia including medication, tube feeds, potassium supplements, and red blood cell transfusion during or within 24 hours after LR administration were recorded. ResultsSerum potassium prior to LR use was highly correlated and predictive of the serum potassium after LR use [P < 0.0001; Odds Ratio 6.77 (3.73 – 12.28)]. Sixteen encounters (5%) developed de-novo hyperkalemia following LR use. No significant positive correlation between the amount of LR administered and the development of hyperkalemia was found. ConclusionsLR use was not independently associated with the development of hyperkalemia in patients with reduced kidney function.

Course of Hyperkalemia in Patients on Hemodialysis.

Background Evidence of longitudinal serum potassium (sK+) concentrations in hyperkalemic hemodialysis patients is sparse. Objective These post hoc analyses of the placebo arm of the phase 3b DIALIZE study (NCT03303521) explored the course of hyperkalemia in hemodialysis patients receiving placebo. Methods In DIALIZE, 196 patients receiving hemodialysis three times weekly were randomized to placebo or sodium zirconium cyclosilicate 5 g starting dose once daily on nondialysis days for 8 weeks. In these post hoc analyses of placebo patients overall (n = 86) and by predialysis sK+ subgroups at randomization <5.5 mmol/L, 5.5 to <6.0 mmol/L, 6.0 to <6.5 mmol/L, and ≥6.5 mmol/L, we assessed mean predialysis sK+ concentration by visit and the proportions of patients with mean predialysis sK+ ranges of 4.0–5.0 and 4.0–5.5 mmol/L by visit. Results In placebo patients, the mean predialysis sK+ concentration at randomization was 5.9 mmol/L, and 5.8 mmol/L at the end of the study (day 57). For placebo patients overall and across all predialysis sK+ subgroups, the mean predialysis sK+ concentration remained ≥5.0 mmol/L for all visits over 8 weeks. Overall, 7–21% and 27–62% of placebo patients had predialysis sK+ ranges of 4.0–5.0 and 4.0–5.5 mmol/L, respectively, at any visit. The proportions of placebo patients with either predialysis sK+ range were greatest for those who were least hyperkalemic (<5.5 mmol/L) and generally decreased with increasing predialysis sK+ concentration. Conclusions Patients receiving placebo and hemodialysis maintained high predialysis sK+ concentrations over 8 weeks following a hyperkalemic event. Most placebo patients remained hyperkalemic and may be at continued risk of adverse events.

Zirconium cyclosilicate: An oral sorbent for potassium, four decades in the making.

HemoCleanse collaborated with Dr. John Sherman and Union Carbide in the 1980s to develop a cation exchanger with high selectivity for potassium and ammonium, for use in a wearable artificial kidney. Synthetic zeolites had unexpected solubility in this application but by 2000, UOP (a sister company of Union Carbide) had developed zirconium cyclosilicate (SZC). HemoCleanse performed early animal studies of SZC as an oral sorbent. These showed remarkable binding characteristics. HemoCleanse then obtained the license for SZC for medical applications, helped to form ZS Pharma, and collaborated in further animal studies and clinical trials. AstraZeneca purchased ZS Pharma in 2015, and SZC (Lokelma®) has now become an effective treatment for hyperkalemia in patients with kidney failure and cardiac conditions.

Electrocardiography is Unreliable to Detect Potential Lethal Hyperkalemia in Patients with Non-dialysis Chronic Kidney Disease.

Hemodialysis patients with hypercalcemia are less likely to manifest the usual electrocardiographic changes associated with hyperkalemia than in those with normal renal function. This study was conducted to determine whether electrocardiography (ECG) is a reliable indicator to detect severe life-threatening hyperkalemia in non-dialysis CKD patients. The study was conducted at three referral university hospitals between July 2017 and June 2018. Severe hyperkalemia was defined as serum potassium concentration ≥ 8.0mEq/L. Serum potassium, sodium, bicarbonate, calcium, and creatinine concentrations were measured and simultaneous 12-lead ECG was obtained. Patients with end-stage renal disease receiving renal replacement therapy were excluded. Also excluded were patients with the usual ECG abnormalities to hyperkalemia. Of the 438 patients screened, 10 (2.3%) aged 2-14years with severe hyperkalemia and normal ECG findings were identified. Median serum potassium level was 8.6mEq/L (range 8.2-9.0). All had regular sinus rhythm. P, QRS, ST segment, T morphology, PR and QT interval, and QRS duration were all normal. Hyperkalemia was associated with CKD, metabolic acidosis, and hypercalcemia in all cases. Therapy with intravenous 0.9% saline, sodium bicarbonate, glucose, insulin, calcium, and salbutamol corrected the hyperkalemia in 7 patients. The remaining three patients evinced arrhythmias requiring hemodialysis. Although rare, non-dialysis CKD patients with hypercalcemia may not manifest the usual electrographic abnormalities associated with hyperkalemia. Thus, a normal ECG finding in non-dialysis CKD patients should be interpreted with caution.

Predictors of hyperkalemia after total parathyroidectomy in patients with drug-refractory secondary hyperparathyroidism.

The purpose of this retrospective study was to explore the primary possible risk factors for the development of postoperative hyperkalemia after total parathyroidectomy with autotransplantation (TPTX + AT) in patients with drug-refractory secondary hyperparathyroidism (SHPT). The clinical data of 149 patients receiving maintenance dialysis for drug-refractory SHPT, who underwent TPTX + AT, were reviewed and analyzed. Demographic data, dialysis status, and laboratory test indices were collected from enrolled patients. According to the postoperative serum potassium level >5.3 mmol/L or not, they were divided into hyperkalemia group and non-hyperkalemia group. The differences in general clinical data and laboratory indicators between the two groups were compared; logistic regression analysis was performed to analyze the risk factors affecting the development of postoperative hyperkalemia in patients; receiver operating characteristic (ROC) subject workup curves were analyzed for the threshold values of postoperative hyperkalemia. Of the 149 participants, 25 (16.78%) developed postoperative hyperkalemia after TPTX + AT. Univariate analysis suggested that dialysis duration, SHPT duration, dialysis modality, and preoperative alkaline phosphatase, blood potassium, and blood calcium levels were independently associated with the development of hyperkalemia after TPTX + AT. Univariate logistic analysis suggested that dialysis duration [odds ratio (OR) 1.18, 95% confidence interval (CI): 1.03, 1.35, P=0.014], preoperative blood potassium (OR 4.95, 95% CI: 2.05, 11.96, P<0.001), and preoperative blood calcium (OR 16.17, 95% CI: 1.36, 191.58, P=0.027) were 3 factors that predicted hyperkalemia after TPTX + AT. According to ROC curve analysis, the optimal cutoff point for dialysis duration was 8.5 years, the optimal cutoff level for preoperative blood potassium was 4.57 mmol/L, and the optimal cutoff level for preoperative blood calcium was 2.31 mmol/L. Of these 3 factors, preoperative blood potassium had a more balanced sensitivity, specificity, and optimal diagnostic efficacy. Patients with drug-refractory SHPT are prone to hyperkalemia after TPTX + AT. Duration of dialysis and preoperative blood potassium and blood calcium levels can help predict the development of postoperative hyperkalemia.

Incidence and risk factors for hyperkalaemia in patients treated for COVID-19 with nafamostat mesylate.

What is known and objectiveNafamostat mesylate (NM) is used clinically in combination with antiviral drugs to treat coronavirus disease (COVID‐19). One of the adverse events of NM is hyperkalaemia due to inhibition of the amiloride‐sensitive sodium channels (ENaC). The incidence and risk factors for hyperkalaemia due to NM have been studied in patients with pancreatitis but not in COVID‐19. COVID‐19 can be associated with hypokalaemia or hyperkalaemia, and SARS‐CoV‐2 is thought to inhibit ENaC. Therefore, frequency and risk factors for hyperkalaemia due to NM may differ between COVID‐19 and pancreatitis. Hyperkalaemia may worsen the respiratory condition of patients. The objective of this study was to determine the incidence and risk factors for hyperkalaemia in COVID‐19 patients treated with favipiravir, dexamethasone and NM.MethodsThis retrospective study reviewed the records of hospitalized COVID‐19 patients treated with favipiravir and dexamethasone, with or without NM, between March 2020 and January 2021. Multivariable logistic regression analysis was performed to identify the risk factors for hyperkalaemia.Results and DiscussionOf 45 patients who received favipiravir and dexamethasone with NM for the treatment of COVID‐19, 21 (47%) experienced hyperkalaemia. The duration of NM administration was a significant predictor of hyperkalaemia (odds ratio: 1.55, 95% confidence interval: 1.04–2.31, p = 0.031). The receiver‐operating characteristic curve analysis determined that the cut‐off value for predicting the number of days until the onset of hyperkalaemia was 6 days and the area under the curve was 0.707.What is new and conclusionThis study revealed that the incidence of hyperkalaemia is high in patients treated for COVID‐19 with NM, and that the duration of NM administration is a key risk factor. When NM is administered for the treatment of COVID‐19, it should be discontinued within 6 days to minimize the risk of hyperkalaemia.

Prescription patterns of sodium and calcium polystyrene sulfonate in patients with hyperkalemia and chronic kidney disease receiving RAAS inhibitors.

ABSTRACTBackgroundSodium and calcium polystyrene sulfonate (SPS/CPS) cation-exchange resins have had long-standing clinical use for hyperkalemia in patients with chronic kidney disease (CKD). However, uncertainty exists regarding the real-world usage of SPS/CPS for acute and chronic management of hyperkalemia. We evaluated the prescription patterns of SPS/CPS and their impact on renin–angiotensin–aldosterone system inhibitor (RAASi) treatment in patients with CKD Stages G3–G5 after an episode of de novo hyperkalemia.MethodsWe conducted a retrospective cohort study using population-level administrative databases in Manitoba, Canada, which included adults with CKD and a RAASi prescription who had an episode of de novo hyperkalemia (≥5.5 mmol/L) between January 2007 and December 2017.ResultsA total of 10 009 individuals were included in our study cohort. Among the study population, 4% received an SPS/CPS prescription within 30 days of their hyperkalemia episode. Of those, 22% received a 1-day supply of SPS/CPS and 7% received a prescription for more than 30 days. There were 8145 patients using RAASi at baseline who survived 90 days after their first hyperkalemia episode. Of those, 1447 (18%) discontinued their RAAS inhibitor and 339 (5%) received a prescription of SPS/CPS. Also, the proportion of patients who discontinued their RAASi was similar among those who did and did not receive a prescription of SPS/CPS.ConclusionIn patients with CKD receiving RAASi therapy, there is a low frequency of SPS/CPS prescription after an episode of hyperkalemia. RAASi discontinuation or downtitration is the most used pharmacologic approach for the management of hyperkalemia, a strategy that deprives patients of the cardiac and renal protective benefits of RAASi. New options for the management of hyperkalemia in this population are needed.

5 versus 10 Units of Intravenous Insulin for Hyperkalemia in Patients With Moderate Renal Dysfunction.

A reduced dose of 5 units of intravenous (i.v.) insulin has been widely accepted for treatment of hyperkalemia in those with end-stage renal dysfunction. However, there remains a dearth of data for patients with moderate renal dysfunction (estimated glomerular filtration rate 15-59 mL/min/m2). Describe the incidence of hypoglycemia and relative change in serum potassium when using 5 vs. 10 units of insulin for hyperkalemia in patients with moderate renal dysfunction. This was a single-center, retrospective study evaluating adult patients with moderate renal dysfunction who received i.v. insulin for treatment of hyperkalemia. Patients were analyzed based on whether they received 5 or 10 units of i.v. insulin. The primary outcome was the rate of hypoglycemia in each group. Secondary outcomes included rate of relative potassium-lowering effect and incidence of severe hypoglycemia. Hypoglycemia occurred in 12 patients who received 5 units of i.v. insulin and 16 patients who received 10 units of i.v. insulin (6.5% vs. 8.4%, p=0.476). Serum potassium was significantly reduced when utilizing 10 units over 5 units of i.v. insulin (-0.9 mmol/L vs. -0.63 mmol/L, p=0.001). Severe hypoglycemia was seen in two encounters in both the 5-unit and 10-unit groups (1.1% vs. 1.0%, p=0.979). There was no difference in hypoglycemic events among patients with moderate renal dysfunction receiving 5 vs. 10 units of i.v. insulin for hyperkalemia. However, 10 units of i.v. insulin lowered serum potassium significantly more than 5 units of i.v. insulin.

Prevalence, Incidence, and Outcomes of Hyperkalaemia in Patients with Chronic Heart Failure and Reduced Ejection Fraction from a Spanish Multicentre Study: SPANIK-HF Design and Baseline Characteristics.

Hyperkalaemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) as it limits the use of some prognostic-modifying drugs and has a negative impact on prognosis. The objective of the present study was to estimate the prevalence of hyperkalaemia in outpatients with HFrEF and its impact on achieving optimal medical treatment. For this purpose, a multicentre, prospective, and observational study was carried out on consecutive HFrEF patients who were monitored as outpatients in heart failure (HF) units and who, in the opinion of their doctor, received optimal medical treatment. A total of 565 HFrEF patients were included from 16 specialised HF units. The mean age was 66 ± 12 years, 78% were male, 45% had an ischemic cause, 39% had atrial fibrillation, 43% were diabetic, 42% had a glomerular filtration rate < 60 mL/min/1.7 m2, and the mean left ventricular ejection fraction was 31 ± 7%. Treatment at the study entry included: 76% on diuretics, 13% on ivabradine, 7% on digoxin, 18.9% on angiotensin-conversing enzyme inhibitors (ACEi), 11.3% on angiotensin receptors blockers (ARBs), 63.8% on angiotensin-neprilysin inhibitors (ARNi), 78.5% on mineralocorticoid receptor antagonists (MRAs), and 92.9% on beta-blockers. Potassium levels in the baseline analysis were: ≤5 mEq/L = 80.5%, 5.1–5.4 mEq/L = 13.8%, 5.5–5.9 mEq/L = 4.6%, and ≥6 mEq/L = 1.06%. Hyperkalaemia was the reason for not prescribing or reaching the target dose of an MRAs in 34.8% and 12.5% of patients, respectively. The impact of hyperkalaemia on not prescribing or dropping below the target dose in relation to ACEi, ARBs, and ARNi was significantly less. In conclusion, hyperkalaemia is a frequent problem in the management of patients with HFrEF and a limiting factor in the optimisation of medical treatment.

Seasonal Changes in the Prevalence of Hyperkalemia in the Emergency Department: A Single Center Study.

Background: Hyperkalemia is an electrolyte disorder frequently encountered in the emergency department. There are few studies on seasonal variation in the prevalence of hyperkalemia. The aim of this study was to investigate the seasonal changes in the prevalence of hyperkalemia in the emergency department. Materials and Methods: We retrospectively reviewed a total of 24,085 patients presented to the emergency department between January 2012 and December 2020. Age, gender, serum potassium level, and serum creatinine level were recorded. The definition used for hyperkalemia was a serum potassium level of ≥ 5.5 mEq/L. Renal function was divided into two categories: preserved (eGFR ≥ 60 mL/min/1.73 m2) or reduced (eGFR < 60 mL/min/1.73 m2). Results: The prevalence of hyperkalemia was 2.1% in patients with preserved renal function and was 11.9% in patients with reduced renal function (p < 0.001). The prevalence of hyperkalemia was highest in winter, followed by spring, autumn, and summer in patients with preserved renal function (p < 0.001) and those with reduced renal function (p < 0.001). There was a linear correlation between monthly weather temperature and the prevalence of hyperkalemia in patients with preserved renal function (r = −0.392; p < 0.001) and those with reduced renal function (r = −0.487; p < 0.001). Conclusions: we found that the prevalence of hyperkalemia was significantly higher in winter for both patients with preserved renal function and those with reduced renal function.

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.

Kidney and heart failure outcomes associated with SGLT2 inhibitor use.

Chronic kidney disease (CKD) and heart failure affect many people worldwide. Despite the availability of pharmacological treatments, both diseases remain associated with considerable morbidity and mortality. After observations that sodium-glucose co-transporter 2 (SGLT2) inhibitors - originally developed as glucose-lowering agents - improved cardiovascular and renal outcomes in patients with type 2 diabetes, dedicated trials were initiated to evaluate the cardiovascular and kidney protective effects in patients with CKD or heart failure. The results of these clinical trials and subsequent detailed analyses have shown that the benefits of SGLT2 inhibitors are consistent across many patient subgroups, including those with and without type 2 diabetes, at different stages of CKD, and in patients with heart failure with preserved or reduced ejection fraction. In addition, post-hoc analyses revealed that SGLT2 inhibitors reduce the risk of anaemia and hyperkalaemia in patients with CKD. With respect to their safety, SGLT2 inhibitors are generally well tolerated. More specifically, no increased risk of hypoglycaemia has been observed in patients with CKD or heart failure without diabetes and they do not increase the risk of acute kidney injury. SGLT2 inhibitors therefore provide clinicians with an exciting new treatment option for patients with CKD and heart failure.