Non-steroidal mineralocorticoid antagonists and hyperkalemia monitoring in chronic kidney disease patients associated with type II diabetes: a narrative review.

Chronic kidney disease (CKD) is a prevalent complication of Type II diabetes (T2D). The coexistence of CKD with T2D is comparable to cardiovascular disease (CVD) when the estimated glomerular filtration rate declines below 60 ml/min/1.73 m2. Screening and early detection of people with high risk for CKD would be beneficial in managing CKD progress and the associated complications such as CV complications. Renin-angiotensin-aldosterone system inhibitors (RAASi) have demonstrated beneficial effects in delaying CKD progression, but they carry the risk of hyperkalemia. Nonsteroidal mineralocorticoid antagonists (nsMRA), such as finerenone, exhibit considerable efficacy in their anti-inflammatory, antifibrotic, and renal protective effects with demonstrable reductions in CV complications. In addition, nsMRAs do not cause significant changes in serum potassium levels compared to traditional steroidal MRA. Ongoing research explores the capacity of the sodium-glucose transport protein 2 inhibitors (SGLT-2i), combined with nsMRA, to produce synergistic renal protective effects and reduce the risk of hyperkalemia. Also, a dedicated renal outcomes study (FLOW study) involving a once-weekly injectable Glucagon-like peptide-1 receptor agonist, semaglutide, was halted early by the data monitoring committee due to having achieved the predefined efficacy endpoint and considerations related to renal disease. In CKD patients with T2D on nsMRA, hyperkalemia management requires a comprehensive approach involving lifestyle adjustments, dietary modifications, regular serum potassium level monitoring, and potassium binders, if necessary. Withholding or down-titration of nsMRAs with close monitoring of serum potassium levels may be required in patients with concerning potassium levels. In light of the current state of knowledge, this review article explores the perspectives and approaches that HCPs may consider when monitoring and managing hyperkalemia in CKD patients with T2D.

Chronic Kidney Disease (CKD) is a common and serious problem among people with Type II Diabetes (T2D). People who have CKD with T2D are at a higher risk for heart disease after normal kidney function declines below certain levels. Renin-angiotensin-aldosterone system inhibitors are a group of medications that can help delay CKD progression but may cause a rise in circulating potassium levels. Nonsteroidal mineralocorticoid antagonist (nsMRA), such as finerenone, can reduce kidney inflammation and damage, with noted cardiovascular benefits, and with less effect on serum potassium levels as compared to their steroid-based counterparts. Researchers are studying whether combining blood sugar medications such as sodium-glucose transport protein-2 inhibitors (SGLT-2i) and finerenone can help protect the kidneys and heart. They also want to see if this combination can prevent high potassium levels. This article talks about ways to check and monitor potassium levels in CKD patients with T2D who may be taking nsMRA. To manage high potassium levels in people with CKD and T2D, doctors may suggest lifestyle changes, dietary adjustments, potassium-lowering medication, or adjustment of other medications with close monitoring of potassium levels.

Potassium-lowering effects of sodium zirconium cyclosilicate in the early post-transplant period.

PROBLEM: Hyperkalemia is a serious condition among intra-abdominal transplant recipients, and the safety and efficacy of sodium zirconium cyclosilicate (SZC) for its management during the early post-transplant period are not well-established. METHODS: Adults who received at least one 10-g dose of SZC within 14 days after an intra-abdominal transplant between January 2020 and July 2022 were included in our study. The primary outcome was the change in potassium (K+) levels following the first SZC dose. Other analyses explored adjunctive potassium-lowering therapies, potential gastrointestinal complications, and patient subgroups based on therapy and transplant type. RESULTS: Among the recipients (n = 46), 11 were kidney recipients, 26 were liver recipients, seven were simultaneous liver/kidney recipients, and two were simultaneous pancreas/kidney recipients. The mean time to first dose post-transplant was 7.6 (±4) days, and the mean change in serum K+ after the initial SZC dose was -.27 mEq (p = .001). No gastrointestinal complications were observed following the SZC dose. The mean increase in serum bicarbonate was .58 mEq (p = .41) following the first dose of SZC. Four kidney recipients required dialysis following the SZC dose. CONCLUSION: This study represents the largest investigation on the use of SZC in transplant recipients. A single 10-g dose of SZC reduced serum K+ levels in all subgroups, while the use of adjunctive K+-lowering therapies did not provide additional reduction beyond the effects of SZC. Importantly, no gastrointestinal complications were observed. These findings suggest that SZC may be a safe and promising therapeutic option for hyperkalemia management following solid organ transplantation.

Safety and efficacy of sodium zirconium cyclosilicate for the management of acute and chronic hyperkalemia in children with chronic kidney disease 4-5 and on dialysis.

BACKGROUND: Sodium zirconium cyclosilicate (SZC), an ion-exchange resin, is effective in the control of hyperkalemia in adults with chronic kidney disease (CKD); reports of use in children are limited. Prolonged therapy with SZC to relax dietary potassium restriction in CKD has not been examined. METHODS: We conducted a retrospective chart review of patients 6 months to 18 years of age with CKD stage 4-5 or on dialysis (5D) administered SZC for sustained hyperkalemia (potassium ≥ 5.5 mEq/L, three consecutive values). Patients received SZC (0.5-10 g per dose; age-based) either short-term (< 30 days) or long-term (> 30 days). RESULTS: Twenty patients with median age 10.8 (inter-quartile range 3.9, 13.4) years were treated with SZC. Short-term SZC, for 5 (3, 19) days, was associated with safe management of dialysis catheter insertions (n = 5) and access dysfunction (n = 4), and was useful during palliative care (n = 1). Serum potassium levels decreased from 6.7 (6.1, 6.9) to 4.4 (3.7, 5.2) mEq/L (P < 0.001). Long-term SZC for 5.3 (4.2, 10.1) months achieved decline in serum potassium from 6.1 (5.8, 6.4) to 4.8 (4.2, 5.4) mEq/L (P < 0.001). SZC use was associated with liberalization of diet (n = 6) and was useful in patients with poor adherence to dietary restriction (n = 3). Adverse events or edema were not observed; serum sodium and blood pressure remained stable. CONCLUSIONS: SZC was safe and effective for the management of acute and chronic hyperkalemia in children with CKD4-5/5D. Its use was associated with relaxation of dietary potassium restriction. Studies to examine its routine use to improve diet and nutritional status in children with CKD are required.

"Ion-Flux": The natural course of ECG changes in severe hypokalemia.

Whereas the electrocardiogram (ECG) changes in hypokalemia are well known, they often receive less attention than the more striking features of hyperkalemia. Furthermore, there is a need for further discussion as to the subtleties of ECG changes that can aid in the differential diagnoses. This case study presents the ECG changes of a patient with severe hypokalemia due to diarrhea. It highlights how bifid T-waves in hypokalemia can be distinguished from other conditions such as coronary artery disease or pericarditis. Furthermore, it also shows the gradual reversal of ECG changes in the same patient when potassium is normalized.

Fifth-time redo mitral valve replacement via right thoracotomy under systemic hyperkalemia cardiopulmonary bypass without aortic cross-clamp.

The surgical management of prosthetic valvular endocarditis (PVE) can be challenging. We report a case of a 46-year-old female patient who had a history of four cardiac operations. We chose a mitral valve replacement via right thoracotomy to enable optimal exposure of the mitral valve (MV). Because of multi-reoperations, we employed systemic hyperkalemia for cardiac arrest to protect the heart during cardiopulmonary bypass (CPB) without aortic cross-clamping. Here, we present a complex operation that performed management of CPB under hyperkalemia and the patient had a good postoperative recovery.

Impact of treatment of hyperkalaemia on quality of life: design of a prospective observational cohort study of long-term management of hyperkalaemia in patients with chronic kidney disease or chronic heart failure in Japan.

INTRODUCTION: Hyperkalaemia (HK) is a frequent complication in patients with chronic kidney disease (CKD) and/or chronic heart failure (CHF). HK must be managed, both to protect patients from its direct clinical adverse outcomes and to enable treatment with disease-modifying therapies including renin-angiotensin-aldosterone system inhibitors. However, the experiences of patients undergoing treatment of HK are not clearly understood. Optimising treatment decisions and improving long-term patient management requires a better understanding of patients' quality of life (QOL). Thus, the aims of this research are: (1) to describe treatment patterns and the impact of treatment on a patient's QOL, (2) to study the relationships between treatment patterns and the impact of treatment on a patient's QOL and (3) to study the relationships between the control of serum potassium (S-K) and the impact of treatment on a patient's QOL, in patients with HK. METHODS AND ANALYSIS: This is a prospective cohort study with 6 months of follow-up in 30-40 outpatient nephrology and cardiology clinics in Japan. The participants will be 350 patients with CKD or CHF who received their first potassium binders (PB) prescription to treat HK within the previous 6 months. Medical records will be used to obtain information on S-K, on treatment of HK with PBs and with diet, and on the patients' characteristics. To assess the impact of treatment on a patient's QOL, questionnaires will be used to obtain generic health-related QOL, CKD-specific and CHF-specific QOL, and PB-specific QOL. Multivariable regression models will be used to quantify how treatment patterns and S-K control are related to the impact of treatment on a patient's QOL. ETHICS AND DISSEMINATION: Institutional review boards at all participating facilities review the study protocol. Patient consent will be obtained. The results will be published in international journals. TRIAL REGISTRATION NUMBER: NCT05297409.

Chronic hyperkalemia, diagnosis and management. Colombian consensus.

OBJECTIVE: Generate recommendations for the diagnosis, management, and follow-up of chronic hyperkalemia. METHOD: This consensus was made by nephrologists and cardiologists following the GRADE methodology. RESULTS: Chronic hyperkalemia can be defined as a biochemical condition with or without clinical manifestations characterized by a recurrent elevation of serum potassium levels that may require pharmacological and or non-pharmacological intervention. It can be classified as mild (K+ 5.0 to < 5.5 mEq/L), moderate (K+ 5.5 to 6.0 mEq/L) or severe (K+ > 6.0 mEq/L). Its incidence and prevalence have yet to be determined. Risk factors: chronic kidney disease, chronic heart failure, diabetes mellitus, age ≥ 65 years, hypertension, and drugs that inhibit the renin angiotensin aldosterone system (RAASi), among others. There is no consensus for the management of chronic hyperkalemia. The suggested pattern for patients is to identify and eliminate or control risk factors, provide advice on potassium intake and, for whom it is indicated, optimize RAASi therapy, administer oral potassium binders and correct metabolic acidosis. CONCLUSIONS: The recommendation is to pay attention to the diagnosis, management, and follow-up of chronic hyperkalemia, especially in patients with risk factors.

OBJETIVO: Generar recomendaciones para el diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica. MÉTODO: Este consenso fue realizado por nefrólogos y cardiólogos siguiendo la metodología GRADE. RESULTADOS: La hiperkalemia crónica puede definirse como una condición bioquímica, con o sin manifestaciones clínicas, caracterizada por una elevación recurrente de las concentraciones séricas de potasio que puede requerir una intervención farmacológica, no farmacológica o ambas. Puede clasificarse en leve (K+ 5,0 a < 5,5 mEq/l), moderada (K+ 5,5 a 6,0 mEq/l) o grave (K+ > 6,0 mEq/l). Su incidencia y prevalencia no han sido claramente determinadas. Se consideran factores de riesgo la enfermedad renal crónica, la insuficiencia cardiaca crónica, la diabetes mellitus, la edad ≥ 65 años, la hipertensión arterial y el tratamiento con inhibidores del sistema renina-angiotensina-aldosterona (iSRAA), entre otros. No hay consenso sobre el manejo de la hiperkalemia crónica. Se sugiere identificar y eliminar o controlar los factores de riesgo, brindar asesoramiento sobre la ingesta de potasio y, para quien esté indicado, optimizar la terapia con iSRAA, administrar aglutinantes orales del potasio y corregir la acidosis metabólica. CONCLUSIONES: Se recomienda prestar atención al diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica, en especial en los pacientes con factores de riesgo.

Radiopacity of Sodium Zirconium Cyclosilicate in Computed Tomography: a case of a patient with Hyperkalemia and kidney disease.

Sodium Zirconium Cyclosilicate (SZC) is commonly used for treating hyperkalemia because it sequesters gastrointestinal potassium ions, thereby reducing serum potassium levels. However, a less-discussed aspect of SZC is its radiopacity on x-ray-based imaging techniques. The European Medicines Agency (EMA) has only vaguely addressed this issue. Radiopaque substances like SZC can interfere with diagnostic imaging, creating challenges for clinicians and radiologists. We present the case of a 34-year-old Italian male to illustrate these concerns.

[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.

Evaluating renin and aldosterone levels in children with organic acidemia-therapeutic experience with fludrocortisone.

Hyporeninemic hypoaldosteronism has been reported in only a few cases with methylmalonic acidemia (MMA) and has been attributed to the renal involvement. This study aims to investigate renin-aldosterone levels along with the renal functions of the patients with organic acidemia. This is a cross-sectional study conducted in patients with MMA, propionic acidemia (PA), and isovaleric acidemia (IVA). Serum renin, aldosterone, sodium, and potassium levels were measured, and glomerular filtration rates (GFR) were calculated. Comparisons were made between the MMA and non-MMA (PA+IVA) groups. Thirty-two patients (MMA:PA:IVA = 14:13:5) were included. The median GFR was significantly lower in the MMA group than in the non-MMA group (p < 0.001). MMA patients had the highest incidence of kidney damage (71.4%), followed by PA patients (23%), while none of the IVA patients had reduced GFR. GFR positively correlated with renin levels (p = 0.015, r = 0.433). Although renin levels were significantly lower in the MMA group than the non-MMA group (p = 0.026), no significant difference in aldosterone levels was found between the two groups. Hyporeninemic hypoaldosteronism was found in 3 patients with MMA who had different stages of kidney damage, and fludrocortisone was initiated, which normalized serum sodium and potassium levels.  Conclusions: This study, which has the largest number of patients among the studies investigating the renin-angiotensin system in organic acidemias to date, has demonstrated that hyporeninemic hypoaldosteronism is not a rare entity in the etiology of hyperkalemia in patients with MMA, and the use of fludrocortisone is an effective treatment of choice in selected cases. What is Known: • Hyperkalemia may be observed in cases of methylmalonic acidemia due to renal involvement and can be particularly prominent during metabolic decompensation. • Hyporeninemic hypoaldosteronism has been reported to be associated with hyperkalemia in only a few cases of methylmalonic acidemia. What is New: • Hyporeninemic hypoaldosteronism was found in one-fifth of cases with methylmalonic acidemia. • Fludrocortisone therapy leads to the normalization of serum sodium and potassium levels.

Potassium level changes in chronic kidney disease patients following balanced crystalloid administration in the emergency department.

One common reason why clinicians are often hesitate to administer balanced crystalloids in the emergency department is the potential occurrence of unexpected hyperkalemia in patients with chronic kidney disease (CKD). In order to investigate the changes in potassium levels resulting from the administration of balanced crystalloids, specially Plasma Solution A (a generic version of Plasma-Lyte), to emergency department patients with CKD, we conducted an evaluation. A retrospective cohort study was conducted at a single academic hospital. Our study included patients with CKD who received intravenous Plasma Solution A and underwent electrolyte follow-up testing within 24 hours of administration. In total, there were 745 patients included in this study, of whom 87 had CKD. Through a 1:1 propensity score matching procedure for factors other than the estimated glomerular filtration rate, we matched 87 patients with normal kidney function to 87 CKD patients. For patients with CKD, the mean standard deviation SD administered volume of Plasma Solution A was 28.7 (21.0) mL/kg, and the mean SD administration duration was 13.2 (4.5) hours. The mean SD potassium level decreased from 4.3 (0.6) mmol/L to 4.1 (0.6) mmol/L (P = .029). Our study findings suggest that there may be no significant harmful increase in potassium levels or worsening of renal function within 24 hours after the intravenous administration of approximately 2 L of Plasma Solution A to patients with CKD.

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.

Maintaining Renin-Angiotensin-Aldosterone System Inhibitor Treatment with Patiromer in Hyperkalaemic Chronic Kidney Disease Patients: Comparison of a Propensity-Matched Real-World Population with AMETHYST-DN.

INTRODUCTION: Guideline-directed renin-angiotensin-aldosterone system inhibitor (RAASi) therapy is rarely achieved in clinical settings, often due to hyperkalaemia. We assessed the potassium binder, patiromer, on continuation of RAASi therapy in hyperkalaemic patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) in the AMETHYST-DN trial, propensity score-matched to a real-world cohort not receiving patiromer (Salford Kidney Study). METHODS: The phase 2, open-label AMETHYST-DN trial (NCT01371747) randomized 304 adults with CKD on RAASi, T2DM, hyperkalaemia (serum potassium [sK+] >5.0 mEq/L), and hypertension to receive patiromer, 8.4-33.6 g/day for 12 months. Patients underwent propensity score matching for systolic blood pressure (BP), heart failure status, and estimated glomerular filtration rate (eGFR), with 321 patients with CKD, T2DM, hyperkalaemia, and on RAASi from a prospective CKD cohort (Salford Kidney Study). Changes in RAASi utilization, sK+, BP, proteinuria, and eGFR during 12-month follow-up were assessed by Mann-Whitney U or χ2 tests. RESULTS: Matching produced 135:135 patients with no significant differences in age, sex, systolic BP, sK+, eGFR, or heart failure status, although differences in diastolic BP remained (p < 0.001). After 12 months, 100% of AMETHYST-DN patients receiving patiromer remained on RAASi therapy, whereas 38.5% of the Salford Kidney Cohort discontinued RAASi (p < 0.001); hyperkalaemia contributed in 16% of patients (42% of RAASi discontinuations). Significantly greater reductions in sK+ and BP, but not proteinuria or eGFR, were observed in AMETHYST-DN, compared with Salford Kidney Study patients (p < 0.05). CONCLUSIONS: These results demonstrate the benefit of patiromer for sK+ management to enable RAASi use while revealing beneficial effects on BP.

[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.

Hyperkalemia in chronic kidney disease: a focus on potassium lowering pharmacotherapy.

INTRODUCTION: Hyperkalemia is one of the most common electrolyte disorders in chronic kidney disease (CKD) and is associated with serious adverse outcomes. Hyperkalemia risk is even greater when CKD patients also have additional predisposing conditions such as diabetes or heart failure. Renin-angiotensin-aldosterone-system blockers are first-line treatments for cardio- and nephroprotection, but their use is often limited due to K+ elevation, resulting in high rates of discontinuation. AREAS COVERED: This article provides an overview of factors interfering with K+ homeostasis and discusses recent data on newer therapeutic agents used for the treatment of hyperkalemia. A detailed literature search was performed in two major databases (PubMed/MEDLINE and Scopus) up to April 2023. EXPERT OPINION: Major clinical trials have tested new and promising kidney protective therapies such as sodium/glucose-cotransporter-2 inhibitors and mineralocorticoid-receptor-antagonists, with promising results. Until recently, the only treatment option for hyperkalemia was the cation-exchanging resin sodium-polystyrene-sulfonate. However, despite its common use, the efficacy and safety data of this drug in the long-term management of hyperkalemia are scarce. During the last decade, two novel orally administered K+-exchanging compounds (patiromer and sodium-zirconium-cyclosilicate) have been approved for the treatment of adults with hyperkalemia, as they both effectively reduce elevated serum K+ and maintain chronically K+ balance within the normal range with an excellent tolerability and no serious adverse events.