Calcineurin inhibitor-related hyperkalemia is caused by hyporeninemic hypoaldosteronism and fludrocortisone is an effective treatment: Report of a case series and review of the literature.

INTRODUCTION: Calcineurin inhibitors (CNIs) are widely used in transplantation. Although CNI-related hyperkalemia is common (10%-60.6%), the underlying pathogenetic mechanism is not well-elucidated and may lead to dose adjustment or treatment withdrawal. OBJECTIVE: The aim of this study is to describe CNI-related hyperkalemia due to hyporeninemic hypoaldosteronism in pediatric transplant recipients who were successfully treated with fludrocortisone. METHOD: In a total of 55 hematopoietic stem cell (HSCT) and 35 kidney transplant recipients followed according to institutional immunosuppression protocols, recipients diagnosed with CNI-related hyperkalemia were reviewed. Recipients who were receiving intravenous fluid, potassium, or were diagnosed with hemolysis, acute graft rejection, or had an eGFR < 30 mL/min/1.73m2, were excluded. A detailed analysis of clinical history as well as biochemical studies was carried out to reveal possible pathophysiology. RESULTS: Three pediatric transplant recipients (one HSCT, two kidney transplantation) with findings of hyperkalemia, hyponatremia, and a mild elevation in blood urea nitrogen while on CNIs were recruited. Urinary potassium excretion was diminished while sodium excretion was increased. Plasma aldosterone levels were low, and renin was not increased in response. Primary adrenal insufficiency was ruled out, and hyporeninemic hypoaldosteronism was diagnosed. CNI-related hyperkalemia was detected earlier in case 1, who had HSCT (22 days), than in the second and third cases, who had kidney transplantation (24 and 30 months post-transplantation, respectively). The discrepancy was hypothesized to be explained by higher overall CNI dose due to higher serum target CNI used in HSCT than kidney transplantation. Electrolyte imbalance was reversed upon administration of physiologic dose fludrocortisone (0.05 mg, daily), while fludrocortisone was ceased after CNI withdrawal in case 1, which is additional evidence for the etiological association of CNIs and hyporeninemic hypoaldosteronism. CONCLUSION: Our three cases strengthen the premise that CNI-related hyperkalemia may be due to hyporeninemic hypoaldosteronism, and the timing and severity may be related to CNI dose. Fludrocortisone is a safe and effective treatment in CNI-related hyperkalemia, providing maintenance of CNIs, which are one of the essential therapeutic agents for pediatric transplantation.

Acquired hyperkalaemia leading to periodic paralysis: an emergency department perspective.

Hyperkalaemia is one of the common electrolyte imbalances dealt with in the emergency department and is caused by extracellular accumulation of potassium ions above normal limits usually greater than 5.0-5.5 mmol/L. It is found in a total of 1-10% of hospitalised patients usually associated with chronic kidney disease and heart failure. The presentation can range from being asymptomatic to deadly arrhythmias. The appearance of symptoms depends on the rate of change rather than just the numerical values. The rare presentation includes periodic paralysis characterised by the sudden onset of short-term muscle weakness, stiffness or paralysis. Management goals are directed towards reducing potassium levels in emergency settings and later on avoiding the triggers for future attacks. In this case, we present a man in his 50s with the generalised weakness later on diagnosed as hyperkalaemic periodic paralysis secondary to tumour lysis syndrome. Emergency physicians dealing with common electrolyte imbalances should keep a sharp eye on their rare presentation and their precipitating factors and should act accordingly.

Hyperkalemia Recurrence Following Medical Nutrition Therapy in Patients with Stage 3-4 Chronic Kidney Disease: The REVOLUTIONIZE I Real-World Study.

INTRODUCTION: The REVOLUTIONIZE I study aimed to characterize the relationships between medical nutrition therapy (MNT) and hyperkalemia recurrence in patients with stage 3-4 chronic kidney disease (CKD) and hyperkalemia who received MNT in real-world clinical practice. METHODS: This observational cohort study used de-identified electronic health record data from patients aged ≥ 18 years with stage 3-4 CKD who received MNT between January 2019 and October 2022 and had hyperkalemia (serum potassium > 5.0 mmol/L) within 30 days before MNT. Patients were followed for 6 months or until the first censoring event (death, prescription of outpatient potassium binder, or study end). The primary outcome was the percentage of patients with ≥ 1 hyperkalemia recurrence during follow-up. Secondary outcomes included the number of hyperkalemia recurrences per patient, time to each recurrence, and hyperkalemia-related healthcare resource utilization. Exploratory outcomes included all-cause healthcare resource utilization and mortality. RESULTS: The final cohort comprised 2048 patients; 1503 (73.4%) patients remained uncensored after 6 months. During the 6-month follow-up period, 56.0% of patients had ≥ 1 hyperkalemia recurrence and 37.4% had ≥ 1 recurrence within the first month. Patients with ≥ 1 hyperkalemia recurrence during follow-up had a mean ± standard deviation (SD) of 2.6 ± 2.2 recurrences. The mean ± SD time to first hyperkalemia recurrence was 45 ± 46 days; the time between recurrences decreased with subsequent episodes. Hyperkalemia-related hospitalizations and emergency department visits were recorded for 13.7% and 1.5% of patients, respectively. Sensitivity analyses showed that results were consistent across patient subgroups, including those with comorbid heart failure and patients receiving renin-angiotensin-aldosterone system inhibitor therapy at baseline. CONCLUSION: Most patients with stage 3-4 CKD had hyperkalemia recurrence, and MNT alone was inadequate to prevent recurrence. These patients may require additional long-term treatment, such as novel potassium binders, to maintain normokalemia and prevent hyperkalemia recurrence following MNT. Infographic available for this article. INFOGRAPHIC.

Patients with chronic kidney disease (CKD) typically receive dietary counseling from a registered dietician, referred to as medical nutrition therapy, to help reduce their risk of complications of CKD while addressing their specific nutritional needs. Patients with CKD have an increased risk of elevated blood potassium levels (hyperkalemia), which has potentially life-threatening consequences. Although medical nutrition therapy may help patients with hyperkalemia to manage their dietary potassium intake, its effects in preventing recurrence are unclear. Our aim was to determine whether medical nutrition therapy can help prevent hyperkalemia recurrence after an initial event in patients with non-dialysis-dependent (stage 3­4) CKD in real-world clinical practice. We used data from de-identified electronic health records to study hyperkalemia recurrence over 6 months in patients with stage 3­4 CKD who received medical nutrition therapy within 30 days after experiencing hyperkalemia. Over half of the patients (56.0%) had at least one hyperkalemia recurrence within an average of 45 days during the 6 months after medical nutrition therapy; these patients had an average of 2.6 distinct recurrences in 6 months. In patients with two or more hyperkalemia recurrences, the time between these became shorter than 30 days. Our real-world study results show that hyperkalemia is a chronic, recurring condition in patients with stage 3­4 CKD, and that medical nutrition therapy is not enough to prevent its recurrence. This suggests that these patients may need additional long-term treatment for hyperkalemia, such as novel potassium binder therapy, to prevent hyperkalemia recurrence.

A rare case of essential thrombocythemia with pseudo-hyperkalemia.

Essential thrombocythemia (ET) is a rare clonal stem cell disorder that affects the production of platelets in the bone marrow. This condition causes an overproduction of platelets, which can lead to blood clots and other complications. Potassium, on the other hand, is an essential mineral that plays a vital role in various bodily functions, including nerve impulses and muscle contractions. Here, in this case report, we investigated a case of pseudo-hyperkalemia caused by essential thrombocythemia in a 77-year-old woman with very high platelet counts. Moreover, this case report, which has no similar examples in the literature review, is important for clinicians.

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.

Response to "Plant-based diets and postprandial hyperkalemia".

Diet therapy for hyperkalemia in people with chronic kidney disease (CKD) has shifted considerably in recent years with the observations that reported potassium intake is weakly, or not at all, associated with plasma potassium levels in this population. One of the lingering debates is whether dietary potassium presents a risk of hyperkalemia in the postprandial state. Although there is general agreement about the need for additional research, the commentary by Varshney et al contends that the available research sufficiently demonstrates that high-potassium plant foods do not pose a risk of postprandial hyperkalemia. Others argue that this remains unsettled science. Although the traditional approach of providing people with CKD lists of high-potassium foods to limit or avoid may be unnecessary, those at high risk of hyperkalemia should be encouraged to consume balanced meals and control portions, at least until some of the key research gaps in this area are resolved. This editorial critiques the analyses offered by Varshney et al and explains the rationale for a more cautious approach to care.

SGLT2 Inhibition and Kidney Potassium Homeostasis.

Pharmacologic inhibition of the sodium-glucose transporter 2 (SGLT2) in the proximal tubule brings about physiologic changes predicted to both increase and decrease kidney K + excretion. Despite these effects, disorders of plasma K + concentration are an uncommon occurrence. If anything, these drugs either cause no effect or a slight reduction in plasma K + concentration in patients with normal kidney function but seem to exert a protective effect against hyperkalemia in the setting of reduced kidney function or when given with drugs that block the renin-angiotensin-aldosterone axis. In this review, we discuss the changes in kidney physiology after the administration of SGLT2 inhibitors predicted to cause both hypokalemia and hyperkalemia. We conclude that these factors offset one another, explaining the uncommon occurrence of dyskalemias with these drugs. Careful human studies focusing on the determinants of kidney K + handling are needed to fully understand how these drugs attenuate the risk of hyperkalemia and yet rarely cause hypokalemia.

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.

Management of hyperkalemia in children.

PURPOSE OF REVIEW: Hyperkalemia is a potentially fatal electrolyte abnormality with no standardized management. The purpose of this review is to provide the knowledge needed for timely and effective management of hyperkalemia in children. It describes the utility of existing and novel therapies. RECENT FINDINGS: Two newer oral potassium binding agents, patiromer sorbitex calcium and sodium zirconium cyclosilicate, have been FDA-approved for the management of hyperkalemia in adults. These newer agents offer hope for improved management, even though their use in pediatric patients requires further exploration. SUMMARY: This review highlights the causes and life-threatening effects of hyperkalemia and provides a comprehensive overview of the management of hyperkalemia in both acute and chronic settings along with upcoming treatment strategies.

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.

"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.