Multicentre, observational, retrospective cohort of hyperkalaemia burden at haemodialysis facility-level in China: the Visualize-HD study protocol.

OBJECTIVES: Hyperkalaemia is a potentially life-threatening disorder in patients undergoing haemodialysis (HD). Excess mortality and hospitalisation have been associated with hyperkalaemia (HK) after the long (2-day) interdialytic interval (LIDI) in patients on thrice a week HD compared with the short (1-day) interdialytic interval. Moreover, not much research has been conducted in China on the descriptive epidemiology and management of HK among different HD centres. The aim of this study is to address this evidence gap by investigating the risk factors associated with HK clinical burden at the HD facility level, current HD centres management patterns, serum potassium management patterns, as well as the risk factors associated with crude mortality in China. DESIGN: Multicentre, observational, retrospective cohort study. SETTING: This study plans to enrol 300 HD centres across China. Haemodialysis centres having ≥100 patients on maintenance HD within 3 years before study initiation, with participation willingness, routine blood collection post-LIDI and death records will be included. PARTICIPANTS: Patients aged ≥18 years and on chronic HD for ≥3 months will be considered eligible. Summary data about serum potassium, characteristics of patients, facility practice patterns will be collected at HD facility level and death records will be at the patient level. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome will be to examine the association between suspected risk factors and HK prevalence at HD facility level. Suspected risk factors include dialysis prescriptions and serum potassium testing frequency, characteristics of patients and related medication usage. The secondary outcome will be to determine the HK prevalence, serum potassium management pattern and risk factors associated with crude mortality. The primary and secondary outcomes will be analysed using regression models. Exploratory outcomes will further investigate the risk factors associated with serum potassium ≥6.0 and ≥6.5 mmol/L. CONCLUSION: The study is expected to provide insights to improve dialysis practice patterns and understand the clinical burden of HK. ETHICS AND DISSEMINATION: This study protocol was reviewed and approved by the Institutional Review Boards and Ethics Committee of Peking University People's Hospital (Approval number: 2020PHB324-01). The results will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05020717.

Nitrogen-Phosphorus-Potassium containing liquid fertilizer intoxication presenting with extreme hyperkalemia, metabolic acidosis and ECG changes.

Liquid fertilizers are widely used for fertilizing in- and outdoor vegetation. Despite the easy accessibility and widespread use, serious intoxications are rare. This case report describes a 61-year-old woman who was treated for life-threatening hyperkalemia, metabolic acidosis and ECG changes after intentional ingestion of liquid fertilizer. Our case shows that intake of liquid fertilizer, though infrequent, can cause serious, life threatening complications.

Tumor lysis syndrome in premature infant prompting early resection of a large sacrococcygeal teratoma: a case report.

BACKGROUND: Sacrococcygeal teratomas (SCTs) are the most common congenital neoplasm and often require resection soon after birth. There are rare reports of cardiac arrest during surgery due to manipulation of the tumor triggering secondary necrosis and hyperkalemia. CASE PRESENTATION: This case describes a very preterm infant with a SCT who develops spontaneous preoperative tumor lysis syndrome (TLS). The medical team utilized rasburicase and the patient underwent total gross resection at 40 h of life. CONCLUSIONS: We emphasize the importance of the early recognition and management of tumor lysis syndrome in SCT with rasburicase, aggressive management of hyperkalemia and consideration of early resection of SCTs even in the case of a very premature infant.

[Hyperkaliemia in hypertensive patients : more than a coincidence?] / Hyperkaliémie chez le patient hypertendu : plus qu'une coïncidence ?

Hyperkaliemia is a relatively common electrolyte disorder whose manifestations and consequences can be serious if severe hyperkalemia is not treated. In the context of hypertension, it is important to look for co-morbidities and conditions favoring hyperkaliemia, to review the drugs prescribed that could contribute to potassium elevation and to bear in mind that when the common causes have been excluded, a genetic origin may be present. In this article, the focus is on the association of hypertension and hyperkaliemia, in the context of the marketing of new cardiovascular and renal drugs that may induce this electrolyte disorder.

L'hyperkaliémie représente un trouble électrolytique relativement fréquent dont les manifestations et conséquences peuvent être graves si l'hyperkaliémie sévère n'est pas corrigée. Dans le contexte d'une hypertension, il faut rechercher les comorbidités et les conditions favorisant l'hyperkaliémie, revoir les médicaments prescrits qui pourraient contribuer à l'élévation du potassium et garder en mémoire que lorsque les causes fréquentes ont été exclues, une origine génétique peut être présente. Dans cet article, l'accent est mis sur l'association de l'hypertension et l'hyperkaliémie, dans le contexte de la mise sur le marché de nouveaux médicaments dans les domaines cardiovasculaire et rénal qui pourraient favoriser la survenue de ce trouble électrolytique.

Admission plasma potassium and length of hospital stay: a meta-analysis.

OBJECTIVE: Hypokalaemia and hyperkalaemia ('dyskalaemia') are commonly seen in patients requiring emergency hospital admission. The adverse effect of dyskalaemia on mortality is well described but there are few data for the effect on hospital length of stay. We sought to determine the association of serum potassium concentration with in-hospital length of stay. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A structured search of MEDLINE, PubMed and SCOPUS databases to 19 March 2021. ELIGIBILITY CRITERIA: Observational cohort studies defining exposure of interest as serum potassium levels (at admission or within the first 72 hours) and with outcome of interest as length of hospital stay. Studies had to provide estimates of length of stay as a comparison between normokalaemia and defined ranges of hyperkalaemia or hypokalaemia. DATA EXTRACTION AND SYNTHESIS: We identified 39 articles published to March 2021 that met the inclusion and exclusion criteria. Study selection, data extraction and quality assessment were carried out by two reviewers working independently and in duplicate, to assessed eligibility and risk of bias, and extract data from eligible studies. Random effects models were used to pool estimates across the included studies. Meta-analyses were performed using Cochrane-RevMan. RESULTS: Five studies were included in the meta-analysis. Compared with the reference group (3.5-5.0 mmol/L), the pooled raw differences of medians were 4.45 (95% CI 2.71 to 6.91), 1.99 (95% CI 0.03 to 3.94), 0.98 (95% CI 0.91 to 1.05), 1.51 (95% CI 1.03 to 2.0), 1 (95% CI 0.75 to 1.25) and 2.76 (95% CI 1.24 to 4.29) for patients with potassium levels of <2.5, 2.5 to <3.0, 3.0 to <3.5, <5 to 5.5, <5.5 to 6 and >6.0 mmol/L, respectively. CONCLUSION: Hospital length of stay follows a U-shaped distribution, with duration of admission being twofold greater at the extremes of the potassium range.

[Neonatal systemic pseudohypoaldosteronism type I]. / æ–°ç”Ÿå„¿å¤šè„å™¨åž‹å‡æ€§é†›å›ºé ®å‡å°‘ç—‡â 型.

An 18-day-old male infant was admitted to the hospital due to recurrent hyperkalemia for more than 10 days. The neonate had milk refusal and dyspnea. The blood gas analysis revealed recurrent hyperkalemia, hyponatremia and metabolic acidosis. Adrenocortical hormone replacement therapy was ineffective. Additional tests showed a significant increase in aldosterone levels. Family whole exome sequencing revealed that the infant had compound heterozygous in the SCNNIA gene, inherited from both parents. The infant was diagnosed with neonatal systemic pseudohypoaldosteronism type I. The infant's electrolyte levels were stabilized through treatment with sodium polystyrene sulfonate and sodium supplement. The infant was discharged upon clinical recovery. This study provides a focused description of differential diagnosis of salt-losing syndrome in infants and introduces the multidisciplinary management of neonatal systemic pseudohypoaldosteronism type I.

Hyperkalaemia prevalence and dialysis patterns in Chinese patients on haemodialysis: an interim analysis of a prospective cohort study (PRECEDE-K).

BACKGROUND: Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis. METHODS: Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum-dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI]). RESULTS: At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum-dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1- < 2, 2- < 3, 3- < 4, and ≥ 4 mmol/L in 13.6%, 45.1%, 35.7%, and 5.2% of patients, respectively; mean: 2.8 mmol/L). The intradialytic sK reduction was 1- < 3 mmol/L for most patients (0- < 1, 1- < 2, 2- < 3, and ≥ 3 mmol/L in 24.2%, 62.2%, 12.8%, and 0.9% of patients, respectively; mean: 1.4 mmol/L). CONCLUSIONS: Hyperkalaemia after a LIDI was common in this real-world cohort of Chinese patients despite standard adequate haemodialysis, and led to large serum-dialysate potassium gradients and intradialytic sK shifts. Previous studies have shown hyperkalaemia and sK fluctuations are highly correlated with poor prognosis. Effective potassium-lowering treatments should be evaluated for the improvement of long-term prognosis through the control of hyperkalaemia and sK fluctuations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04799067.

Effects of sodium-glucose co-transporter-2 inhibitors by background cardiovascular medications: A systematic review and meta-analysis.

AIM: To explore whether the beneficial cardiovascular (CV) effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors is consistent with or without concurrent use of CV medications in patients with type 2 diabetes, heart failure (HF) or chronic kidney disease. METHODS: We searched Medline and Embase up to September 2022 for CV outcomes trials. The primary endpoint was the composite of cardiovascular (CV) death or hospitalization for HF. Secondary outcomes included the individual components of CV death, hospitalization for HF, death from any cause, major adverse CV events or renal events, volume depletion and hyperkalaemia. We pooled hazard ratios (HRs) and risk ratios alongside 95% confidence intervals (CIs). RESULTS: We included 12 trials comprising 83 804 patients. SGLT-2 inhibitors reduced the risk of CV death or hospitalization for HF regardless of background use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), b-blockers, diuretics, mineralocorticoid receptor antagonists (MRAs), or triple combination therapy of either an ACEI/ARB plus b-blocker plus MRA, or an ARNI plus b-blocker plus MRA (HRs ranged from 0.61 to 0.83; P > .1 for each subgroup interaction). Similarly, no subgroup differences were evident for most analyses for the secondary outcomes of CV death, hospitalization for HF, all-cause mortality, major adverse CV or renal events, hyperkalaemia and volume depletion rate. CONCLUSIONS: The benefit of SGLT-2 inhibitors seems to be additive to background use of CV medications in a broad population of patients. These findings should be interpreted as hypothesis generating because most of the subgroups analysed were not prespecified.

Methodology-related pseudohyperkalemia associated with marked muscle enzyme leakage in a dog.

BACKGROUND: As hyperkalemia may be life-threatening, it is critical to recognize artifactually increased potassium concentrations. Pseudohyperkalemia may occur in myopathies when using the VetScan2 analyzer (VS2), but the degree of pseudohyperkalemia and relationships relative to creatine kinase activity (CK) are unknown. OBJECTIVES: We aimed to determine what degree of muscle enzyme leakage, as reflected by increased serum CK activity, results in cases with falsely elevated potassium concentrations when measured by the VS2. We also sought to establish if a linear relationship exists between potassium concentrations measured by the VS2 and CK activity. METHODS: Serum samples from dogs with increased CK activity and with CK activity within the reference interval and without clinically relevant biochemical alterations were used to create diluted samples having various CK activities. Potassium concentrations and CK activities were determined on VS2 and Cobas c501 (Cobas) analyzers. Wilcoxon signed rank, Bland-Altman, and Passing-Bablok analyses were used to compare potassium concentrations generated by the VS2 and Cobas analyzers. Least squares regression analysis was performed to evaluate if a linear relationship exists between VS2 potassium concentrations and Cobas CK activities. RESULTS: Potassium concentrations from the VS2 were higher (median and standard deviation (SD) = 5.2 +/- 0.46 mmol/L) than those from the Cobas analyzer (4.4 +/- 0.35 mmol/L; P < 0.000), and a positive mean bias was found (mean difference = 0.774 mmol/L; 95% Confidence Interval (CI) = 0.706-0.842; limits of agreement = 0.21-1.34). Passing-Bablok regression showed a positive proportional bias for potassium concentrations on the VS2 compared with paired Cobas results (Slope = 1.328; 95% CI = 1.100-1.500) but did not reveal systematic bias (Intercept = -0.714; 95% CI = -1.46-0.265). Least squares regression analysis showed a poor non-significant relationship (R2 = 0.19) between potassium measured by the VS2 and CK measured by the Cobas analyzer. CONCLUSIONS: A defined threshold value of CK activity at which potassium concentration begins to falsely increase when measured on the VS2 was not established as data widely varied. A poor non-significant relationship between potassium concentrations and CK activities did not allow prediction of the threshold at which falsely increased potassium concentrations would be expected on the VS2.

HYPERKALEMIA IN FOUR ANESTHETIZED RED WOLVES (CANIS RUFUS).

Four clinically healthy red wolves (Canis rufus) developed hyperkalemia during routine anesthetic procedures. All cases were anesthetized using a combination of dexmedetomidine (10-24 mcg/kg), ketamine (2-3 mg/kg), and either midazolam (0.25-0.5 mg/kg) or butorphanol (0.2-0.48 mg/kg). Additional anesthetics were given to effect. Total anesthetic time ranged from 60 to 420 min. Three out of four cases were treated using terbutaline (0.01 mg/kg SC), which successfully resolved the hyperkalemia. No bradyarrhythmias were seen in any cases where electrocardiography (ECG) was monitored (3/4). All cases recovered from anesthesia, with one prolonged recovery. All animals are clinically healthy at the time of writing. Factors including anesthetic duration, the use of α-2 agonists, hyperthermia, and genetics are discussed as possible triggers for hyperkalemia. Serial blood gases, with electrolyte measurements, are recommended during anesthesia of red wolves, particularly when anesthetic time may be prolonged or the patient suffers from hyperthermia. Terbutaline appears to be a successful treatment should hyperkalemia arise.

Acute flaccid paralysis due to multifactorial hyperkalaemia.

A male patient in his late 30s with a history of Lynch syndrome and colorectal cancer relapse, which recently started chemotherapy, was admitted to the emergency department with acute lower limb weakness that had progressed to all limbs and resulted in complete flaccid paresis with general areflexia. Blood tests showed severe hyperkalaemia, severe acute kidney injury and hyperuricaemia. Ultrasound showed bilateral hydronephrosis due to pelvic mass obstruction. Hyperkalaemia correction measurements were started as well as rasburicase with the assumption of tumour lysis syndrome and postrenal kidney injury. The patient showed a favourable clinical response with complete return of limb movement in the following hours and progressive recovery of renal function in the following days. This case highlights the need for prompt diagnosis and correction of severe hyperkalaemia, and its multiple possible causes, as it can lead to acute flaccid paralysis and a fatal outcome.

Brugada syndrome uncovered in patient with pseudohypoaldosteronism due to hyperkalaemia.

Brugada syndrome is a rare sodium channelopathy that predisposes to an increased risk of malignant arrythmias and sudden cardiac death. Previous studies have reported that metabolic disturbances can uncover a Brugada ECG pattern. Given the risk of malignant arrhythmias, it is important to correctly diagnose and treat Brugada syndrome. We report a case of Brugada syndrome uncovered by hyperkalaemia precipitated in a patient with pseudohypoaldosteronism.

Medication-Related Adverse Events and Discordancies in Cystatin C-Based vs Serum Creatinine-Based Estimated Glomerular Filtration Rate in Patients With Cancer.

Importance: Serum creatinine-based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C-based eGFR (eGFRcys) is an alternative marker of GFR. Objective: To determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr. Design, Setting, and Participants: This cohort study analyzed adult patients with cancer at 2 major academic cancer centers in Boston, Massachusetts. These patients had their creatinine and cystatin C measured on the same day between May 2010 and January 2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was considered to be the baseline date. Exposure: The primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr. Main Outcomes and Measures: The primary outcome was risk of the following medication-related AEs within 90 days of the baseline date: (1) supratherapeutic vancomycin trough level greater than 30 µg/mL, (2) trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the secondary outcome, a multivariable Cox proportional hazards regression model was used to compare 30-day survival of those with vs without eGFR discordance. Results: A total of 1869 adult patients with cancer (mean [SD] age, 66 [14] years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There were 543 patients (29%) with an eGFRcys that was more than 30% lower than their eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr were more likely to experience medication-related AEs compared with patients with concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin levels greater than 30 µg/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), trimethoprim-sulfamethoxazole-related hyperkalemia (29 of 129 [22%] vs 11 of 92 [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted odds ratio for vancomycin levels more than 30 µg/mL was 2.59 (95% CI, 1.08-7.03; P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; P = .003). Conclusions and relevance: Results of this study suggest that among patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, supratherapeutic drug levels and medication-related AEs occurred more commonly in those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer.

Patiromer utility as an adjunct treatment in patients needing urgent hyperkalaemia management (PLATINUM): design of a multicentre, randomised, double-blind, placebo-controlled, parallel-group study.

INTRODUCTION: Hyperkalaemia is common, life-threatening and often requires emergency department (ED) management; however, no standardised ED treatment protocol exists. Common treatments transiently reducing serum potassium (K+) (including albuterol, glucose and insulin) may cause hypoglycaemia. We outline the design and rationale of the Patiromer Utility as an Adjunct Treatment in Patients Needing Urgent Hyperkalaemia Management (PLATINUM) study, which will be the largest ED randomised controlled hyperkalaemia trial ever performed, enabling assessment of a standardised approach to hyperkalaemia management, as well as establishing a new evaluation parameter (net clinical benefit) for acute hyperkalaemia treatment investigations. METHODS AND ANALYSIS: PLATINUM is a Phase 4, multicentre, randomised, double-blind, placebo-controlled study in participants who present to the ED at approximately 30 US sites. Approximately 300 adult participants with hyperkalaemia (K+ ≥5.8 mEq/L) will be enrolled. Participants will be randomised 1:1 to receive glucose (25 g intravenously <15 min before insulin), insulin (5 units intravenous bolus) and aerosolised albuterol (10 mg over 30 min), followed by a single oral dose of either 25.2 g patiromer or placebo, with a second dose of patiromer (8.4 g) or placebo after 24 hours. The primary endpoint is net clinical benefit, defined as the mean change in the number of additional interventions less the mean change in serum K+, at hour 6. Secondary endpoints are net clinical benefit at hour 4, proportion of participants without additional K+-related medical interventions, number of additional K+-related interventions and proportion of participants with sustained K+ reduction (K+ ≤5.5 mEq/L). Safety endpoints are the incidence of adverse events, and severity of changes in serum K+ and magnesium. ETHICS AND DISSEMINATION: A central Institutional Review Board (IRB) and Ethics Committee provided protocol approval (#20201569), with subsequent approval by local IRBs at each site, and participants will provide written consent. Primary results will be published in peer-reviewed manuscripts promptly following study completion. TRIAL REGISTRATION NUMBER: NCT04443608.

Calcineurin regulates aldosterone production via dephosphorylation of NFATC4.

The mineralocorticoid aldosterone, secreted by the adrenal zona glomerulosa (ZG), is critical for life, maintaining ion homeostasis and blood pressure. Therapeutic inhibition of protein phosphatase 3 (calcineurin, Cn) results in inappropriately low plasma aldosterone levels despite concomitant hyperkalemia and hyperreninemia. We tested the hypothesis that Cn participates in the signal transduction pathway regulating aldosterone synthesis. Inhibition of Cn with tacrolimus abolished the potassium-stimulated (K+-stimulated) expression of aldosterone synthase, encoded by CYP11B2, in the NCI-H295R human adrenocortical cell line as well as ex vivo in mouse and human adrenal tissue. ZG-specific deletion of the regulatory Cn subunit CnB1 diminished Cyp11b2 expression in vivo and disrupted K+-mediated aldosterone synthesis. Phosphoproteomics analysis identified nuclear factor of activated T cells, cytoplasmic 4 (NFATC4), as a target for Cn-mediated dephosphorylation. Deletion of NFATC4 impaired K+-dependent stimulation of CYP11B2 expression and aldosterone production while expression of a constitutively active form of NFATC4 increased expression of CYP11B2 in NCI-H295R cells. Chromatin immunoprecipitation revealed NFATC4 directly regulated CYP11B2 expression. Thus, Cn controls aldosterone production via the Cn/NFATC4 pathway. Inhibition of Cn/NFATC4 signaling may explain low plasma aldosterone levels and hyperkalemia in patients treated with tacrolimus, and the Cn/NFATC4 pathway may provide novel molecular targets to treat primary aldosteronism.

Predicting hyperkalemia in patients with advanced chronic kidney disease using the XGBoost model.

BACKGROUND: Hyperkalemia is a common complication of chronic kidney disease (CKD). Hyperkalemia is associated with mortality, CKD progression, hospitalization, and high healthcare costs in patients with CKD. We developed a machine learning model to predict hyperkalemia in patients with advanced CKD at an outpatient clinic. METHODS: This retrospective study included 1,965 advanced CKD patients between January 1, 2010, and December 31, 2020 in Taiwan. We randomly divided all patients into the training (75%) and testing (25%) datasets. The primary outcome was to predict hyperkalemia (K+ > 5.5 mEq/L) in the next clinic vist. Two nephrologists were enrolled in a human-machine competition. The area under the receiver operating characteristic curves (AUCs), sensitivity, specificity, and accuracy were used to evaluate the performance of XGBoost and conventional logistic regression models with that of these physicians. RESULTS: In a human-machine competition of hyperkalemia prediction, the AUC, PPV, and accuracy of the XGBoost model were 0.867 (95% confidence interval: 0.840-0.894), 0.700, and 0.933, which was significantly better than that of our clinicians. There were four variables that were chosen as high-ranking variables in XGBoost and logistic regression models, including hemoglobin, the serum potassium level in the previous visit, angiotensin receptor blocker use, and calcium polystyrene sulfonate use. CONCLUSIONS: The XGBoost model provided better predictive performance for hyperkalemia than physicians at the outpatient clinic.

Long-term effect of eplerenone treatment in children with chronic allograft nephropathy.

BACKGROUND: Literature supports the protective role of mineralocorticoid antagonist (MRA) against the renal injury induced by aldosterone in kidney transplant recipients. However, there is limited data available regarding the safety and efficacy of MRAs in pediatric renal transplant patients. Therefore, we aimed to investigate the effect of long-term eplerenone administration in children with chronic allograft nephropathy (CAN). METHODS: Twenty-six renal transplant children with biopsy-proven CAN, an estimated glomerular filtration rate (eGFR ) > 40 mL/min per 1.73 m2 and with a significant proteinuria were included. Selected patients were randomly divided into two groups as follows; Group 1 (n = 10) patients received 25 mg/day eplerenone and Group 2 (n = 16) patients did not receive eplerenone for 36 months. Patients were examined in the renal transplant outpatient clinic biweekly for the first month and once a month thereafter. The primary outcome of the patients was compared. RESULTS: Mean eGFR stayed stable in group 1 patients, but significantly decreased in group 2 at 36 months (57.53 ± 7.53 vs. 44.94 ± 8.04 mL/min per 1.73 m2 , p = .001). Similarly, spot protein-creatinine ratio was significantly lower in group 1 compared to group 2 patients at 36 months (1.02 ± 7.53 vs. 3.61 ± 0.53, p < .001). Eplerenone associated hyperkalemia was not observed in group 1 patients (4.6 ± 0.2 vs. 4.56 ± 0.3, p = .713). CONCLUSION: The long-term eplerenone administration blunted the chronic allograft nephropathy by maintaining a stable eGFR levels and decreasing urine protein-creatinine ratio. Eplerenone associated hyperkalemia was not observed in our study.

Comparison of effectiveness and safety of sodium polystyrene sulfonate and sodium zirconium cyclosilicate for treatment of hyperkalemia in hospitalized patients.

PURPOSE: Potassium binders are frequently utilized for the treatment of hyperkalemia in hospitalized patients; however, there is limited data directly comparing individual agents. The purpose of this study was to compare the effectiveness and safety of sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC) for hyperkalemia treatment in hospitalized patients. METHODS: This retrospective cohort study evaluated adult patients who were admitted within a 7-hospital health system and received SPS or SZC for a serum potassium level greater than 5.0 mEq/L. Patients receiving dialysis prior to SPS/SZC administration, those receiving other potassium-lowering medications within 6 hours prior to blood sampling for a repeat potassium level, and those started on kidney replacement therapy prior to sampling for a repeat potassium level were excluded. RESULTS: Following evaluation of 3,903 patients, the mean reduction in serum potassium 4 to 24 hours after binder administration was 0.96 mEq/L with SPS and 0.78 mEq/L with SZC (P < 0.0001). The median dose of SPS was 30 g (interquartile range [IQR], 15-30 g) while the median (IQR) dose of SZC was 10 g (10-10 g). Resolution of hyperkalemia within 24 hours was achieved in a higher percentage of patients with use of SPS (74.9%) versus SZC (68.8%) (P < 0.001). CONCLUSION: One of the largest comparisons of SPS and SZC conducted to date, this study demonstrated the effectiveness and safety of both agents. While a statistically greater reduction in serum potassium was observed with use of SPS, there was significant dosing variability among agents that limited the ability to directly compare specific doses. Further investigation is needed to determine the optimal dose of each agent for acute hyperkalemia management. This data will inform clinical decisions about the choice of potassium binder for acute hyperkalemia.

DIALIZE China: A Phase IIIb, Randomized, Placebo-Controlled Study to Reduce Predialysis Hyperkalemia With Sodium Zirconium Cyclosilicate in Chinese Patients.

PURPOSE: The DIALIZE China study (Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects) (NCT04217590) evaluated sodium zirconium cyclosilicate (SZC) for the management of hyperkalemia in Chinese patients undergoing hemodialysis. METHODS: In the double-blind, Phase IIIb DIALIZE China study, Chinese adults with kidney failure and predialysis hyperkalemia (predialysis serum potassium [sK+] concentration >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after ≥1 short interdialytic interval) who were receiving hemodialysis 3 times weekly were randomized to placebo or SZC 5 g once daily on nondialysis days. Doses were titrated towards maintaining normokalemia for 4 weeks (titration period) in 5-g increments up to 15 g. Primary efficacy was the proportion of responders during the 4-week evaluation period following the titration period (ie, those with a predialysis sK+ of 4.0-5.0 mmol/L for at least 3 of 4 hemodialysis visits following the LIDI) who did not require urgent rescue therapy. FINDINGS: Overall, 134 adults (mean [SD] age, 55 [11.3] years) were randomized to SZC or placebo (n = 67 each). There were significantly more responders with SZC (37.3%) versus placebo (10.4%; estimated odds ratio [OR] = 5.10; 95% CI, 1.90-15.12; P < 0.001). The probability of all predialysis sK+ concentrations being 3.5 to 5.5 mmol/L was significantly higher with SZC versus placebo (estimated OR = 6.41; 95% CI, 2.71-15.12; P < 0.001). A greater proportion of patients achieved an sK+ of 3.5 to 5.5 mmol/L on at least 3 of 4 LIDI visits during evaluation with SZC (73.1%) versus placebo (29.9%). Serious adverse events occurred in 9.1% and 11.9% of patients in the SZC and placebo groups, respectively. IMPLICATIONS: SZC treatment for predialysis hyperkalemia is effective and well tolerated in Chinese patients with kidney failure receiving hemodialysis. CLINICALTRIALS: gov identifier: NCT04217590.