Novel Approaches to Management of Hyperkalaemia in Kidney Transplantation

John Rizk; David Quan; Steven Gabardi; Youssef Rizk; Kamyar Kalantar-Zadeh


Curr Opin Nephrol Hypertens. 2021;30(1):27-37. 

In This Article

Abstract and Introduction


Purpose of Review: Medications used frequently after kidney transplantation, including calcineurin inhibitors, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers and antimicrobials, are considered the leading culprit for posttransplant hyperkalaemia in recipients with a well functioning allograft. Other risk factors include comorbidities such as diabetes, hypertension and heart failure; and consumption of a potassium-enriched diet. We review the mechanisms for hyperkalaemia following kidney transplantation that are addressed using nonpharmacological and pharmacological interventions. We also discuss emerging therapeutic approaches for the management of recurrent hyperkalaemia in solid organ transplantation, including newer potassium binding therapies.

Recent Findings: Patiromer and sodium zirconium cyclosilicate are emerging potassium binders approved for the treatment of hyperkalaemia. Patiromer is a polymer that exchanges potassium for calcium ions. In contrast, sodium zirconium cyclosilicate is a nonpolymer compound that exchanges potassium for sodium and hydrogen ions. Both agents are efficacious in the treatment of chronic or recurrent hyperkalaemia and may result in fewer gastrointestinal side effects than older potassium binders such as sodium polystyrene sulfonate and calcium polystyrene sulfonate. Large-scale clinical studies have not been performed in kidney transplant patients. Patiromer may increase serum concentrations of tacrolimus, but not cyclosporine. Sodium zirconium cyclosilicate does not appear to compromise tacrolimus pharmacokinetics, although it may have a higher sodium burden.

Summary: Patiromer and sodium zirconium cyclosilicate may be well tolerated options to treat asymptomatic hyperkalaemia and have the potential to ease potassium dietary restrictions in kidney transplant patients by maintaining a plant-dominant, heart-healthy diet. Their efficacy, better tolerability and comparable cost with respect to previously available potassium binders make them an attractive therapeutic option in chronic hyperkalaemia following kidney transplantation.


Metabolic derangements can occur following kidney transplantation. The most common posttransplant electrolyte and acid--base disturbances, ranked according to the likelihood of occurrence during the first several months, are hyperkalaemia, hypophosphatemia, hypomagnesemia, metabolic acidosis, hypercalcemia and hyperphosphatemia.[1,2] Hyperkalaemia is defined as a serum potassium concentration of more than 5.3 mEq/l in adults.[3] It is a common, potentially life-threatening complication following transplantation that can lead to clinical manifestations such as haemodynamic instability, central nervous system adverse events and fatal cardiac arrhythmias. Most patients are asymptomatic or manifest nonspecific signs and symptoms, including, skeletal muscle weakness, fatigue, cardiac complications, including bradycardia or other arrhythmias, and impaired gastrointestinal motility.[2]

Kidney transplant recipients are at an increased risk of developing hyperkalaemia due to both pharmacologic and pathophysiological-related mechanisms. The incidence of hyperkalaemia ranges from 25 to 44% in renal transplant recipients receiving a calcineurin inhibitor (CNI).[4,5] Simultaneous kidney-pancreas transplant recipients with bladder drainage are more susceptible to hyperkalaemia, with one study reporting an incidence of 73%.[5] Hyperkalaemia is reported to be prevalent during the first 3 months postkidney transplantation.[5]

In this review, we discuss the cause and management strategies of hyperkalaemia observed after kidney transplantation. We also discuss novel United States Food and Drug Administration (FDA) approved therapies for the management of chronic or recurrent hyperkalaemia, which appear to be well tolerated in this patient population.