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

Pharmacological Management

Acute Management

Calcium, Insulin and Dextrose. Emergent management for hyperkalaemia starts with stabilization of the myocardium using intravenous calcium, which is indicated when the serum potassium is very high, that is more than 6.5 mEq/l.[28] Intravenous calcium gluconate is preferred over calcium chloride because it has a lower osmolality and is less irritating to the veins,[28] although calcium chloride contains three time more elemental calcium than calcium gluconate (27 vs. 9 mg/ml).[29] Insulin administration accelerates the intracellular shift of potassium into the skeletal muscle cells. Glucose is given with insulin only when serum glucose is 250 mg/dl or less.

Sodium Bicarbonate. Hyperkalaemia in the setting of stable renal allograft may indicate metabolic acidosis and the need for sodium bicarbonate therapy.[19] By alkalinizing the serum, bicarbonate may indirectly cause the shift of potassium into cells via an H+/K+ exchange mechanism. In addition, bicarbonate may be directly transported into muscle cells along with potassium.[30] Treatment with sodium bicarbonate was successful in a 61-year-old man undergoing kidney transplantation, who developed hyperkalaemia intraoperatively.[31] Shortly after the start of surgery, an arterial blood gas revealed potassium 7.5 mEq/l, pH 7.28 and bicarbonate 18 mEq/l. Fifty mEq of sodium bicarbonate were used, followed by 25 g of dextrose, 1 g of calcium chloride and 10 units of regular insulin. Subsequent ABGs revealed potassium levels less than 5 mEq/l, and 4 l of 0.45% NaCl, each with 75 mEq bicarbonate, were given intravenously. Postoperatively, the potassium level was 3.8 mEq/l. The most likely cause of this patient's hyperkalaemia was metabolic acidosis, which is evident by his low bicarbonate level. Results of this case report suggest that the use of sodium bicarbonate can be helpful in lowering potassium levels by providing alkaline intravenous fluid to renal transplant patients with metabolic acidosis.

Beta2-agonists. When administered in a nebulizer or metered-dose inhaler, beta-agonists decrease plasma potassium levels transiently but relatively rapidly by shifting potassium intracellularly. Albuterol directly stimulates the Na+/K+-ATPase pump in skeletal muscles, which enhances cellular uptake of potassium. Albuterol's onset of action is usually within 15–30 min, with a peak effect between 30 and 60 min, and its effect lasts for 4–6 h.[32,33] A major concern regarding the use of albuterol is a paradoxical increase in serum potassium concentrations in the first minutes following inhalation.[34,35] Beta2-agonists may provide additive or synergistic hypokalaemic effects when combined with loop diuretics or thiazides.[36]

Acute/Chronic Management

Diuretics. Loop diuretics are useful agents for the acute management of hyperkalaemia, whereas both loops diuretics and thiazides are also potential therapies for the chronic management of hyperkalaemia.[37] In patients with a reduced eGFR less than 45 ml/min/1.73 m2, a loop diuretic is preferred, as thiazides become less effective at such levels of GFR, except for chlorthalidone and indapamide, which are effective to eGFR levels of 30 ml/min/1.73 m2.[38,39] Patients undergoing kidney transplantation are at a higher risk of developing fluid overload.[40] Volume-expanded (i.e. oedema, short-term weight gain) kidney transplant patients with hyperkalaemia can benefit from a loop diuretic, while those who manifest hyperkalaemia, hypertension and acidosis, which are symptoms consistent with sodium-chloride cotransporter activation, may also benefit from thiazides.[20] Thiazides can also be considered in kidney transplant patients with hyperkalemic hypertension and hypomagnesemia, although they increase serum magnesium when used with a CNI.[41]

Fludrocortisone. Fludrocortisone has been used to treat cyclosporine-induced hyperkalaemia,[4,42] and has a proven safety and efficacy in the management of tacrolimus-associated hyperkalaemia with concomitant hyponatremia in kidney transplant patients while maintaining stable tacrolimus trough concentrations.[8] Nevertheless, it is important to monitor tacrolimus levels when initiating fludrocortisone, as corticosteroids may decrease the serum concentration of tacrolimus by inducing the enzymes CYP3A4 and CYP3A5, which are responsible for tacrolimus metabolism. Conversely, tacrolimus concentrations may increase when tapering or discontinuing fludrocortisone, necessitating tacrolimus concentrations and effects to be monitored more frequently.[43] Moreover, fludrocortisone may elevate blood pressure, and its use may be somewhat challenging in hypertensive patients. Concurrent therapy with diuretics (loop and thiazide) will likely have an additive effect to fludrocortisone in inducing renal potassium wasting.

Chronic Management

Sodium Polystyrene Sulfonate. SPS is a nonabsorbable, nonselective cation-exchange resin polymer that has been commonly used to treat chronic hyperkalaemia since the 1950s.[44] SPS exchanges potassium for sodium, but the resin is not exclusively selective for potassium; calcium and magnesium may bind as well, which can lead to overcorrection of potassium, hypocalcaemia or hypomagnesaemia. SPS should be used cautiously in transplant patients because it contains considerable amounts of sodium (100 mg per gram of the drug) and can lead to volume overload and should be used with caution in patients with severe hypertension, congestive heart failure and oedema.[45] In addition, the FDA recommends separating the dosing of SPS from other orally administered medicines by at least 3, or 6 h if the patient has gastroparesis.[46]

SPS-related intestinal necrosis and other serious gastrointestinal events, which are rare, yet catastrophic, complications after renal transplantation, have been reported mainly in small case series especially when used with sorbitol as a carrier. These complications mainly appear on the ileum and colon, but can also affect the upper gastrointestinal tract to cause bleeding, ischemic colitis, focal to deep ulceration, necrosis and perforation, and faecal impaction with rectal stenosis.[47,48] Kidney transplantation and immunosuppression are considered potential risk factors for developing intestinal necrosis after SPS administration.[49] Other risk factors include history of intestinal disease, surgery, hypovolemia and renal failure.[44,47] Therefore, SPS use should be restricted to the inpatient setting excluding the immediate postoperative condition.