Managing Hyperkalemia in the Modern Era: A Case-Based Approach

Abstract

The last decade has seen tremendous advances in the prevention and treatment of recurrent hyperkalemia. In this narrative review, we aim to highlight contemporary data on key areas in the epidemiology and management of hyperkalemia. Focusing on drug-induced hyperkalemia (the implications of renin-angiotensin-aldosterone system inhibitors [RAASi] discontinuation and the role of mineralocorticoid receptor antagonists), newer concurrent therapies that modify potassium handling (sodium-glucose transporter 2 inhibitors [SGLT2i]), the introduction of new treatment agents (oral potassium binding agents), and the controversial role of dietary potassium restriction, we apply recent research findings and review the evidence in a case-based format. The last decade has seen tremendous advances in the prevention and treatment of recurrent hyperkalemia. In this narrative review, we aim to highlight contemporary data on key areas in the epidemiology and management of hyperkalemia. Focusing on drug-induced hyperkalemia (the implications of renin-angiotensin-aldosterone system inhibitors [RAASi] discontinuation and the role of mineralocorticoid receptor antagonists), newer concurrent therapies that modify potassium handling (sodium-glucose transporter 2 inhibitors [SGLT2i]), the introduction of new treatment agents (oral potassium binding agents), and the controversial role of dietary potassium restriction, we apply recent research findings and review the evidence in a case-based format. The kidneys play the pivotal role in maintaining potassium homeostasis and eliminating excess potassium ingested from diet or released from cells. Hyperkalemia is therefore a commonly encountered problem in chronic kidney disease (CKD), particularly in patients with reduced kidney function who are taking medications that alter the kidneys’ ability to eliminate excess potassium. These medications include renin-angiotensin-aldosterone system inhibitors (RAASi), including angiotensin converting enzyme inhibitors (ACEi), and angiotensin II receptor blockers (ARBs); and mineralocorticoid receptor antagonists (MRAs). Unfortunately, patients who often have the most to gain from these therapies, such as those with CKD, diabetic kidney disease (DKD), and heart failure, are also the patients at greatest risk of developing hyperkalemia from RAASi or MRA use. Management of potassium balance is rapidly evolving with new and emerging medications that prevent or directly treat hyperkalemia such as sodium-glucose transporter 2 inhibitors (SGLT2i) and novel gastrointestinal potassium exchangers such as patiromer and sodium zirconium cyclosilicate (SZC). Therefore, clinicians caring for patients with CKD have multiple options at their disposal to control hyperkalemia, without having to revert to potentially unhealthy restrictive dietary changes or removal of RAASi, which have proven long-term benefits. In this narrative review, we focus on the management of recurrent, ambulatory, hyperkalemia, particularly in the context of RAASi use, and evaluate recent evidence on the emerging therapeutics available when faced with hyperkalemia in patients with CKD, along with their advantages and pitfalls summarized in Figure 1. Using a case-based approach, with fictional scenarios typical of the types of patients or consultations nephrologists would encounter in their clinical practice, we focus specifically on the implications of RAASi discontinuation in the face of hyperkalemia, the newer MRAs, the role of SGLTs, oral potassium binders, and the role of dietary potassium restriction. Of note, this review focuses on the management of milder forms of hyperkalemia and not severe, life-threatening hyperkalemia, which can be encountered with acute kidney injury in acutely ill patients. For this, we refer the reader to recent reviews done on the topic.1Dépret F. Peacock W.F. Liu K.D. Rafique Z. Rossignol P. Legrand M. Management of hyperkalemia in the acutely ill patient.Ann Intensive Care. 2019; 9: 32https://doi.org/10.1186/s13613-019-0509-8Crossref PubMed Scopus (55) Google Scholar,2Lemoine L. Le Bastard Q. Batard E. Montassier E. An evidence-based narrative review of the emergency department management of acute hyperkalemia.J Emerg Med. 2021; 60: 599-606https://doi.org/10.1016/j.jemermed.2020.11.028Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar A 63-year-old male with hypertension and presumed diabetic nephropathy with proteinuric CKD (serum creatinine 180 μmol/l, estimated glomerular filtration rate [eGFR] 36 ml/min, urine albumin-to-creatinine ratio 60 mg/mmol) is followed by his primary care physician for blood pressure and diabetes management. Medications include amlodipine 10 mg daily, metformin 500 mg twice daily, and gliclazide 30 mg daily. There is no history of cardiovascular disease or heart failure. Kidney function has slowly worsened over the last few years. Recent blood pressure readings were 140 to 150/85 to 95 mm Hg and subsequently lisinopril 10 mg daily was initiated. On repeat blood testing 3 weeks later, serum potassium was 5.9 mmol/l and then 5.8 mmol/l on repeat testing a few days later with no significant change in eGFR. The patient’s primary care physician discontinues the lisinopril and sends a referral to nephrology for further management of hypertension and hyperkalemia. Hyperkalemia is typically defined as a serum potassium measurement >5.0 to 5.5 mmol/l, depending on the laboratory doing the test, the equipment used, and the population distribution of potassium values used to determine the reference range. Pseudohyperkalemia occurs most often because of blood drawing techniques (fist clenching, use of a tourniquet) which may release potassium from cells causing a false elevation.3Don B.R. Sebastian A. Cheitlin M. Christiansen M. Schambelan M. Pseudohyperkalemia caused by fist clenching during phlebotomy.N Engl J Med. 1990; 322: 1290-1292https://doi.org/10.1056/nejm199005033221806Crossref PubMed Google Scholar,4Wiederkehr M.R. Moe O.W. Factitious hyperkalemia.Am J Kidney Dis. 2000; 36: 1049-1053https://doi.org/10.1053/ajkd.2000.19084Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Other rarer causes of pseudohyperkalemia include thrombocytosis (release from platelets after clotting has occurred, thereby causing elevated serum potassium measurement) and severe leukocytosis (release during blood processing because of cell fragility).5Graber M. Subramani K. Corish D. Schwab A. Thrombocytosis elevates serum potassium.Am J Kidney Dis. 1988; 12: 116-120https://doi.org/10.1016/s0272-6386(88)80005-2Abstract Full Text PDF PubMed Google Scholar,6Kellerman P.S. Thornbery J.M. Pseudohyperkalemia due to pneumatic tube transport in a leukemic patient.Am J Kidney Dis. 2005; 46: 746-748https://doi.org/10.1053/j.ajkd.2005.06.005Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar True hyperkalemia may occur when potassium shifts or gets released outside of cells because of tissue injury or trauma, tumor lysis syndrome, insulin deficiency in diabetes, metabolic acidosis from and to a from severe E. potassium in the of the PubMed Google The tumor lysis Engl J Med. PubMed Scopus Google a for PubMed Google in potassium during acute J Med. 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