
==== Front
World J Transplant
WJT
World Journal of Transplantation
2220-3230
Baishideng Publishing Group Inc

jWJT.v14.i3.eid95905
10.5500/wjt.v14.i3.95905
95905
Minireviews
Disorders of potassium homeostasis after kidney transplantation
Aboghanem A et al. Potassium and kidney transplantation
Aboghanem Abdelhamid School of Medicine, University of Toronto, Toronto M5C 2T2, Ontario, Canada

Prasad G V Ramesh School of Medicine, University of Toronto, Toronto M5C 2T2, Ontario, Canada
Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, Ontario, Canada. ramesh.prasad@unityhealth.to

Author contributions: Aboghanem A critically reviewed and appraised the literature and wrote the paper; Prasad GVR designed the study, critically reviewed and appraised the literature, and wrote the paper. Both authors read and approved the final manuscript.

Corresponding author: G V Ramesh Prasad, MBBS, PhD, Professor, Staff Physician, Kidney Transplant Program, Michael's Hospital, No. 61 Queen Street East, Toronto M5C 2T2, Ontario, Canada. ramesh.prasad@unityhealth.to

18 9 2024
18 9 2024
14 3 9590521 4 2024
29 5 2024
26 6 2024
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Disturbances of potassium balance are often encountered when managing kidney transplant recipients (KTR). Both hyperkalemia and hypokalemia may present either as medical emergencies or chronic outpatient abnormalities. Despite the high incidence of hyperkalemia and its potential life-threatening implications, consensus on its management in KTR is lacking. Hypokalemia in KTR is also well-described, although it is given less attention by clinicians compared to hyperkalemia. This article discusses the etiology, pathophysiology and management of both types of potassium disorders in KTR. Once any emergent situation has been corrected, treatment approaches include correcting insulin deficiency if present, adjusting non-immunosuppressive and immunosuppressive medications, eliminating or supplementing potassium as needed, and dietary counselling. Although commonly of multifactorial etiology, ascertaining the specific cause in a particular patient will help guide successful management. Monitoring KTR through regular laboratory testing is essential to detect serious disturbances in potassium balance since patients are often asymptomatic.

Balance
Dialysis
Hyperkalemia
Hypokalemia
Kidney
Metabolism
Potassium
==== Body
pmc Core Tip: Both hyperkalemia and hypokalemia are usually asymptomatic in kidney transplant recipients but can lead to serious morbidity, so regular monitoring is needed. Since medications are a common cause, dose adjustments or medication changes are often required.

INTRODUCTION

Kidney transplantation (KT) is the treatment of choice for end-stage kidney disease (ESKD)[1]. Successful KT improves quality of life and survival for many ESKD patients compared to long-term dialysis[2]. Among the complications faced by kidney transplant recipients (KTR), an increased susceptibility to hyperkalemia occurs compared to non-KTR with similar kidney function[3]. Hyperkalemia increases patient morbidity and possibly cardiovascular mortality, and also adds to healthcare expenses by delaying discharge from hospital whether it occurs during the first or subsequent admissions. The prevalence of hyperkalemia in KTR is estimated to be between 25% and 44%[4]. Hyperkalemia can occur at any time in the post-transplant period. Many clinicians intervene when plasma or serum potassium levels exceed 5.5 mmol/L[5]. Despite the high incidence of hyperkalemia and its potential life-threatening implications, consensus on its management in KTR is lacking. Hypokalemia in KTR is also well-described, although it is given less attention by clinicians compared to hyperkalemia. This article discusses the pathophysiology and management of both types of potassium disorders in KTR. Hyperkalemia is defined here as a plasma potassium ion (K+) concentration exceeding 5 mmol/L and hypokalemia as K+ less than 3.5 mmol/L.

For this narrative review, we surveyed the published English literature using PubMed and Medline (1965-2024) using the search terms potassium, hyperkalemia, hypokalemia, and transplantation to identify the most relevant articles for inclusion. Criteria for selection included relevance to kidney pathophysiology and clinical practice.

HYPERKALEMIA

Etiology

The major causes of post-transplant hyperkalemia are summarized in Table 1. Frequently prescribed post-transplant medications, including calcineurin inhibitors (CNI), sulfa antibiotics, and antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and beta blockers are common etiologic culprits for post-transplant hyperkalemia even in KTR with a well-functioning graft. Simultaneous kidney-pancreas transplant recipients with bladder drainage may have an incidence of up to 73%[4]. Hyperkalemia may be more frequent in KTR with delayed graft function. Dietary non-adherence when present along with other risk factors[5], transcellular K+ shifts from uncontrolled diabetes or intraoperative mannitol use, and metabolic acidosis are other common causes[6].

Table 1 Causes of hyperkalemia in kidney transplant recipients

Category	Examples	
Type of transplant	Combined kidney-pancreas	
Immunosuppressive medications	Cyclosporine	
	Tacrolimus	
Non-immunosuppressive medications	Angiotensin-converting enzyme inhibitors	
	Angiotensin II receptor blockers	
	Beta-blockers	
	Steroidal mineralocorticoid antagonists (eplerenone, spironolactone)	
	Non-steroidal mineralocorticoid antagonists (finerenone)	
	Potassium-sparing diuretics (amiloride, triamterene)	
	Heparin	
	Mannitol	
	Non-steroidal anti-inflammatory drugs	
	Pneumocystis jirovecii pneumonia prophylactic agents (pentamidine, trimethoprim-sulfamethoxazole)	
	Succinylcholine	
Others	Interstitial fibrosis and tubular atrophy	
	Delayed graft function	
	Dietary indiscretion1	
	Hyperglycemia	
	Metabolic acidosis	
	Type 4 renal tubular acidosis	
	Urinary tract obstruction	
1 In combination with at least one other factor.

Pathophysiology

Potassium homeostasis: Potassium is the predominant intracellular cation, with a concentration of 140–150 mmol/L intracellularly and 3.5–5 mmol/L extracellularly. Serum K+ is slightly elevated compared to plasma K+ due to K+ release from clotted red blood cells. A high intracellular K+ concentration maintained by Na/K-ATPase establishes the resting membrane potential essential for cellular excitability and contraction. K+ enters the body through diet, and kaliuresis results in K+ leaving the body, with a lesser amount leaving via the colon. Since the ratio of intracellular to extracellular K+ concentration substantially impacts the resting membrane potential, a stable plasma K+ concentration is essential to optimal cellular function[7].

Mannitol: Acute hyperkalemia in the early post-transplant phase is not uncommon. Mannitol is often used during the KT operative procedure as an osmotic diuretic to improve renal blood flow and reduce warm ischemia related injury[8], although its use is controversial[9]. Mannitol can cause intraoperative hyperkalemia[10], even leading to cardiac arrest[11]. Possible mechanisms include hemolysis from its hypertonicity, acidosis from dilution of bicarbonate as a consequence to the desired temporary intravascular volume expansion, and solvent drag[11]. Hypertonic mannitol also decreases sodium reabsorption if significant native kidney function is present, and there may be dilution of plasma proteins, decreased blood viscosity, release of prostaglandins and atrial natriuretic factor, and renin-angiotensin system inhibition[12]. Mannitol through solvent drag moves water and K+ out of cells, and this movement is exacerbated by concomitant hyperglycemia. Mannitol use remains popular however due to a reduced incidence of delayed graft function and acute kidney injury[13].

Insulin deficiency: Dietary K+ is normally absorbed by the gastrointestinal tract, then rapidly taken up by muscle and liver cells, facilitated by insulin and beta-2 adrenergic receptors. Most K+ load is excreted renally, being tightly regulated predominantly in the connecting tubule and cortical collecting duct. Aldosterone, along with adequate distal water and sodium delivery are crucial determinants to renal K+ secretion. Dietary K+ is not a significant determinant of plasma K+ unless renal function is impaired[14]. Sodium reabsorption via the epithelial sodium channel (ENaC) establishes the electrical gradient required for K+ secretion. Hyperkalemia can thereby result from insulin deficiency, inorganic metabolic acidosis, diminished glomerular filtration rate (GFR), and reduced distal sodium delivery. In KTR, hyperkalemia can however result from type 4 renal tubular acidosis (RTA) from CNI, even in the absence of any of these other risk factors[15]. Insulin deficiency or resistance can hinder the translocation of K+ to the intracellular compartment, resulting in post-transplant hyperkalemia along with hyperglycemia, especially in KTR with diabetes[16].

Non-immunosuppressive medications: Medications contribute significantly to hyperkalemia even in KTR with well-functioning grafts. Trimethoprim in trimethoprim/sulfamethoxazole (TMP/SMX) being structurally similar to amiloride and triamterene, competitively blocks ENaC, diminishing the lumen-negative voltage in the cortical distal nephron (CDN) critical to K+ secretion[17]. This mechanism holds true for pentamidine, also used for prophylaxis against Pneumocystis jirovecii pneumonia (PJP)[18]. Depressed GFR, hyporeninemic hypoaldosteronism, and a low flow rate in the CDN from intravascular volume depletion combine to affect the luminal fluid's osmole content and potentially increase TMP concentration in the CDN, enhancing further its ability to block ENaC. ACE inhibitors and ARB are popular drugs for KTR[19], but increase plasma K+ due to impaired K+ secretion[20]. Heparin is commonly administered to hospitalized patients. KTR with poor mobility may receive subcutaneous heparin, and complications such as deep vein thrombosis and pulmonary embolism often require intravenous (IV) heparin. Although not specifically described in KTR, both unfractionated and low-molecular-weight heparin selectively reduce aldosterone synthesis, and decrease the number and affinity of adrenal angiotensin II receptors[21,22]. Severe hyperkalemia is more likely when kidney function is impaired or when ACE inhibitors, ARB, or potassium-sparing diuretics are used concomitantly. Beta-blockers are also associated with hyperkalemia due to plasma K+ shifts[23] although the evidence for persistent or severe hyperkalemia is low[6].

CNI: CNI (tacrolimus and cyclosporine) are a mainstay of post kidney-transplant immunosuppression, often being prescribed for the life of the allograft. CNI are a well-described cause of hyperkalemia, with up to 32% of KTR receiving cyclosporine experiencing hyperkalemia[24]. Tacrolimus may portend a greater risk than cyclosporine[25]. The sodium chloride cotransporter (NCC)-regulatory kinase (with no lysine) WNK4 is increased[26]. WNK kinases exert their effect on NCC by phosphorylating members of the sterile (STE)-20 superfamily of serine/threonine kinases, specifically the STE20-related proline-alanine-rich-kinase (SPAK) and the oxidative stress response kinase type 1 (OSR1), and they in turn phosphorylate and activate the NCC. WNK4 is the major regulatory kinase of SPAK/OSR1-NCC pathway. CNI increase phosphorylation of the NCC in the first part of the DCT, thereby maintaining its active state[26]. WNK4 in turn is degraded by binding to Kelch-like 3 (KLHL3)[27] and Cullin 3 proteins as part of a E3 ubiquitin ligase complex. The proper functioning of this ubiquitin ligase complex requires the dephosphorylation of KLHL3, a process mediated by protein phosphatase 3 (or calcineurin). CNI maintain KLHL3 in its phosphorylated, inactive state, consequently reducing the degradation of WNK kinases. Increased NaCl reabsorption by NCC leads to volume expansion to suppress renin and aldosterone release, reducing the number of open ENaC units in the luminal membranes of principal cells in the aldosterone-sensitive distal nephron. Atrial natriuretic peptide released in response to volume expansion suppresses renin release and inhibits hyperkalemia-induced aldosterone secretion. Diminished NaCl delivery to the aldosterone sensitive distal nephron decreases the ability to generate a lumen negative voltage. These kinases also cause renal outer medullary potassium (ROMK) endocytosis from the luminal membrane of principal cells. Mineralocorticoid resistance[28,29] combined with metabolic acidosis leads to impaired K+ secretion and hyperkalemic type 4 RTA. CNI also induce afferent renal arteriolar vasoconstriction and exacerbate AKI[30], reducing K+ elimination further. Chronic downregulation of nuclear factor of activated T cells from long-term CNI use leads to renal vasculature hyalinosis, tubular atrophy, interstitial fibrosis, and glomerular thickening[26], all of which associate with worsened renal allograft function[31].

Obstructive uropathy: A type 4 RTA may also occur in patients with obstructive uropathy, a condition to which KTR are prone. In this situation, Type 4 RTA results from a defect in H+ and K+ secretion in the distal nephron, similar to chronic interstitial nephritis, rather than from aldosterone deficiency[32]. Reduced renal blood flow causes ischemia, and T lymphocytes as well as macrophages enter the interstitium. These cells produce transforming growth factor β, leading to progressive fibrosis and reduced glomerular filtration if the obstruction is left unchecked. Patients with type 4 RTA including KTR are often asymptomatic with a normal urine output, but the associated hyperkalemia can still be severe.

Clinical manifestations

Although hyperkalemia often presents asymptomatically, untreated hyperkalemia can quickly cause ascending muscle weakness, parasthesias, decreased reflexes, and ultimately cardiac arrhythmias and fatality[6]. The specific consequences of untreated hyperkalemia to KTR have not been well described. Nonetheless, insights from chronic kidney disease (CKD) populations underscore the importance of maintaining normal serum K+ concentrations[33]. Most post-transplant programs perform regular blood testing as part of their routine monitoring, resulting in a greater likelihood of detecting hyperkalemia compared to other CKD patients as a result of ascertainment bias. However, KTR may present to transplant clinics or emergency departments in the context of acute illness, at which time hyperkalemia may be detected as part of their admission screening. All new KTR should be admitted to either an intensive care or step-down unit with available continuous cardiac rhythm monitoring in the immediate post-operative period, due to the risk for hyperkalemia.

The detection of hyperkalemia warrants urgent assessment, even though symptomatic manifestations directly attributable to the hyperkalemia are rare. After excluding pseudohyperkalemia from sample hemolysis[34], which is typically commented in the laboratory report but is not uncommon in KTR who are subject to poor vascular access. It is important to assess if an emergency situation is present through electrocardiogram (ECG) changes, such as peaked T-waves, widened QRS complexes, prolonged QT-interval, and hidden P-waves[35,36]. Considerable variability exists regarding the plasma K+ concentration required to induce cardiac toxicity. Increased K+ conductance shortens the action potential duration leading to sinus arrest, sinus bradycardia, ventricular fibrillation, and asystole[36].

Management

Cardiac membrane stabilization: An ECG can often be quickly obtained in the hospital immediately post-transplant or even in the outpatient setting, although some outpatient clinics may prefer to send their patients immediately to an emergency department. Successfully handling hyperkalemia revolves around safeguarding against arrhythmias. Intravenous calcium gluconate is commonly used if ECG changes consistent with hyperkalemia are present. Even mild ECG changes can rapidly progress to dangerous arrhythmias. Emergency treatment can be considered even when ECG changes are absent, usually when the K+ is around 6.5 mmol/L, and especially when hypocalcemia, acidemia, and/or hyponatremia are also present. For unclear reasons, patients on chronic hemodialysis may tolerate serious hyperkalemia without adverse effects[37], but it is unclear if this benefit exists in KTR despite their long-standing CKD. Calcium directly antagonizes the adverse myocardial effects that hyperkalemia induces, reducing the threshold potential of cardiac myocytes and thereby stabilizing the membrane potential. This beneficial effect does not depend on a change in serum K+. A typical dose of calcium gluconate is 1000 mg (or 10 mL of a 10% solution) infused over 2 to 3 minutes under cardiac monitoring. If EKG changes persist, the dose can be repeated after 5 minutes.

Shifting potassium into cells: If the serum K+ exceeds 7.0 mmol/L, shifting K+ into cells can proceed simultaneously, but shifting K+ is usually the second step in managing emergent situations. IV short-acting insulin promotes K+ shift into the intracellular space. Due to a fear of hypoglycemia, IV glucose is often administered prior to IV insulin, but great care must be taken to stabilize the cardiac cell membrane first when IV glucose is given prior to administering insulin, since the transient hyperglycemia can shift more K+ out of cells and cause a potentially fatal arrhythmia. Some authors suggest using 5 units or 0.1 units/kg with 50 g dextrose as a bolus, or administering dextrose as an infusion[38]. Patients should be monitored closely for hypoglycemia for at least 4 h. Sufficient evidence from randomized trials of therapy are lacking[39]. Pre-transplant hyperkalemia predicts post-transplant hyperkalemia[40], so the plasma K+ should be kept under 5.5 mmol/L before transplant surgery, if necessary through an extra session of dialysis. Maximizing the K+ gradient through a lower dialysate K+ content and increasing the dialysis blood flow rate[41] may enhance K+ clearance.

Beta-2 adrenergic receptor agonists enhance activation of Na-K ATPase pumps, shifting K+ intracellularly. Nebulized salbutamol is easily available, effective and dose-dependent, acting within 30 minutes and peaking at 60 minutes. Salbutamol at a dose of 10 or 20 mg can reduce plasma K+ by about 1 mmol/L for 2 h, and is considered effective therapy[42]. Although data specific to KTR are lacking, side effects include tremor, tachycardia, and headaches, which may confound tacrolimus-related side effects. Another measure to consider is administering sodium bicarbonate. Elevating extracellular bicarbonate levels increases cellular K+ uptake, although bicarbonate infusion is generally considered ineffective[43,44] especially in isolation, and risks sodium overload and pulmonary edema. Oral sodium bicarbonate (3-5 g/day) in non-emergent situations may be considered adjunctive when concurrent with metabolic acidosis, but there is sparse evidence for this maneuver in KTR.

Potassium elimination: Once the cardiac cell membrane is stable and K+ has shifted intracellularly, focus can then shift to eliminating excess K+ from the body. Dialysis is efficient therapy for hyperkalemia[39], so the availability of dialysis support at the time of transplant surgery must be ensured. Vascular access for dialysis may not be immediately available in KTR transplanted preemptively, and for KTR on peritoneal dialysis (PD), inadvertent nicking of the peritoneal membrane may cause leaking of dialysate and necessitate placing a hemodialysis catheter, rather than continuing PD. At the other end of the transplant life spectrum, patients with failing renal allografts may also require urgent dialysis for hyperkalemia in the absence of viable access, such as from a clotted or immature fistula or graft. Removing K+ via the transplanted kidney by a loop diuretic such as furosemide or bumetanide is often employed, even in the early post-transplant setting. Some evidence of existing or establishing kidney function such as measurable urine output is required however, as well as an adequate blood pressure. Loop diuretics may be used in chronic hyperkalemia in normovolemic or hypervolemic patients, in addition to adding other drugs such as thiazides[45].

Fludrocortisone promotes potassium secretion and can help lower plasma K+ concentration[46]. Evidence for efficacy in KTR is limited primarily to case reports. At a dose of 0.1 mg/day, both acute and chronic hyperkalemia can be effectively managed[47]. Fludrocortisone may address tacrolimus-induced aldosterone resistance, with normokalemia achievable quickly[48]. Since fludrocortisone causes fluid retention, it may be most useful in early post-transplant patients who are also intravascularly volume depleted.

The gastrointestinal tract can also be a useful route for K+ removal. Commonly used agents in the current era include patiromer and sodium zirconium cyclosilicate (ZS-9), with the use of sodium polystyrene sulfonate largely abandoned despite its efficacy with sorbitol, due to concerns over the possibility of intestinal ischemia and thrombosis, leading to bowel necrosis[49]. Patiromer is being used with increasing comfort in KTR based on published clinical experiences[50]. Patiromer is an organic potassium-binding polymer employing calcium as the exchange ion especially in the colon, and so is not particularly helpful in the acute setting. Gastrointestinal side effects are usually limited, but patiromer can cause hypomagnesemia and affect the bioavailability of other drugs[6]. However, there is no clear evidence to-date of interference with immunosuppressive medications. ZS-9 facilitates exchange of H+ and Na+ for K+ and NH4+ throughout the gastrointestinal tract, acting one hour after ingestion, and so may be more useful in the acute setting both for KTR[51] and hospitalized patients more generally[52]. There is no appreciable impact on tacrolimus pharmacokinetics[53]. However, cost remains a concern for using both patiromer and ZS-9.

Adjusting medications: Besides administering new therapies such as those outlined above, adjusting existing medications through discontinuation, switch, or dose reduction is also an important part of hyperkalemia management. TMP and antihypertensive agents are often the first targets of change for clinicians. While TMP/SMX remains the standard for PJP prevention, alternative agents such as dapsone or atovaquone are equally effective. Hyperkalemia is not necessarily dependent on the dose of TMP[54]. Thrice weekly TMP/SMX in the first post-transplant year is a safe and an effective regimen to prevent PJP[55]. Antihypertensives affecting the renin–angiotensin–aldosterone system are typically avoided early post-transplant but may be warranted later for patients with cardiovascular comorbidities. Beta blockers are not typically discontinued early post-transplant unlike ACE or ARB. Adding patiromer or ZS-9 might facilitate continuing these medications over the long term. In cases of mild to moderate hyperkalemia, such medication adjustment can help normalize serum K+ levels without the need for total discontinuation.

Changes in immunosuppressive medication are rarely pursued in response to hyperkalemia given the effectiveness of all the preceding measures, since immunosuppressive medication changes might increase risks for new side effects or even acute rejection. Similarly, the risk of hyperkalemia is typically not considered when selecting de-novo immunosuppressive regimens. Nonetheless, some studies report a lower incidence of hyperkalemia with drugs such as sirolimus[56,57], everolimus[58], and belatacept[59,60], so switches made for this indication are at theoretically feasible.

Dietary modification: Dietary modification can be a very useful adjunct in managing post-transplant hyperkalemia. All KTR with a measured plasma or serum K+ greater than 5.0 mmol/L should receive dedicated dietician counseling, customized to their ethnic and sociocultural background, and be given appropriate dietary information sheets. Repeated consultations might be required if hyperkalemia persists. Such counseling may help prevent visits to the emergency department for severe hyperkalemia.

HYPOKALEMIA

Hypokalemia is characterized by a plasma K+ concentration below 3.5 mmol/L, and can be life-threatening when below < 2.5 mEq/L. In an outpatient population undergoing laboratory testing, nearly 14% exhibit mild hypokalemia. The incidence of hypokalemia is less than that of hypomagnesemia in stable outpatient KTR[61]. Additionally, about 20% of hospitalized patients generally are found to have hypokalemia, but only a small fraction of these instances is clinically significant.

Etiology and pathogenesis

Hypokalemia can be experimentally induced[62], but is rarely seen in healthy subjects. The kidney can minimize potassium excretion to 5 to 25 mmol per day in the presence of total body potassium depletion[62]. Reducing potassium intake to 20 mmol per day therefore seldom results in significant hypokalemia. Enhanced insulin availability promotes K+ entry into skeletal muscle and hepatic cells by increased Na-K-ATPase pump activity, such as when exogenous insulin is administered in severely hyperglycemic states even when there is initial normokalemia or hyperkalemia. However, hypokalemia arising from insulin overdose is rare. Furthermore, endogenous insulin release in response to carbohydrate intake, as observed in refeeding syndrome or administration of dextrose may contribute to hypokalemia. IV potassium is therefore administered using a saline solution rather than dextrose[63-65]. Elevated beta-adrenergic activity and exercise-induced catecholamine surges are some other causes[66,67], though these events are not specific to KTR. Hypokalemia is more severe in patients with pre-existing hypokalemia receiving diuretic therapy[68], and is dose-dependent. Increased gastrointestinal losses due to vomiting, diarrhea, laxatives, or nasogastric tube drainage lead to metabolic alkalosis and substantial urinary potassium losses. Diarrhea from any cause as well as secretions from villous adenomas can be associated with relatively high K+ concentrations due to hyperchloremic metabolic acidosis.

Urinary K+ excretion, mainly regulated by principal cells in the connecting tubule and cortical collecting tubule, is a key determinant of K+ balance. Increased mineralocorticoid activity creates an electronegative lumen that facilitates passive K+ secretion into the tubular lumen through potassium channels such as ROMK. Hypokalemia may result from polyuria when intravascular volume depletion enhances aldosterone secretion. Reduced activity of K+ secretory channels potentially mediated by increased angiotensin II activity may explain the inconsistent occurrence of hypokalemia in primary aldosteronism[69].

The use of both sirolimus[69,70] and everolimus[71] has been associated with hypokalemia. Hypokalemic nephropathy can occur, with tubular vacuolization, reversible with sirolimus discontinuation[72]. Mammalian target of rapamycin, which sirolimus inhibits, plays a role in tubular epithelial cell integrity and regeneration[72]. Although an incidence of up to 50% has been reported with everolimus in antitumour regimens[73], the incidence is likely in the 5%-10% range in KTR[70]. Hypokalemia can occur in KTR due to native renal artery stenosis[74]. Primary aldosteronism may be unmasked by KT[75]. The incidence of hypokalemia in KTR receiving thiazide diuretics can approach 30%[45]. Patients receiving hemodialysis against a low K+ bath, those on PD prior to receiving their transplant, and those requiring plasmapheresis, for example as part of treatment for antibody-mediated rejection, may be at greater risk for hypokalemia. Low dietary potassium intake from failure to unlearn dialysis restrictions post-transplant may lead to hypokalemia, usually when combined with factors.

The major causes of post-transplant hypokalemia are summarized in Table 2.

Table 2 Causes of hypokalemia in kidney transplant recipients

Category	Example	
Potassium loss		
Gastrointestinal	Vomiting	
	Diarrhea	
	Intestinal malabsorption	
	Colostomy	
Renal	Hyperkalemia	
	Hyperreninemia	
	Hyperaldosteronism	
	Renal tubular acidosis (Type 1, 2)	
	Hypomagnesemia	
Medications	Sirolimus	
	Everolimus	
	Loop diuretics	
	Thiazide diuretics	
	Mineralocorticoids	
Inadequate Potassium Intake	Poor oral intake	
	Dietary indiscretion1	
	Total parenteral nutrition	
Intracellular Potassium Shift	Metabolic alkalosis	
	Dextrose solution	
	Insulin therapy	
Others	Dialysis using low potassium bath	
	Peritoneal dialysis	
	Plasmapheresis	
1 In combination with at least one other factor.

Clinical manifestations

Hypokalemia-induced ECG alterations include ST segment depression, diminished T wave amplitude, and increased U wave amplitude, particularly in lateral precordial leads V4 to V6, and QT interval prolongation. Skeletal muscle weakness and atrial fibrillation are sometimes noted. Prolonged hypokalemia impairs urine concentrating ability, and can lead to hypokalemic nephropathy and elevations in blood pressure, as well as decreased phosphate reabsorption. Hypokalemia also reduces insulin secretion and can contribute to glucose intolerance and thiazide-associated diabetes, although whether hypokalemia contributes to the incidence of post-transplant diabetes (PTDM) is unknown.

Management

Immediate measures: Use of balanced solutions rather than normal saline as replacement fluids can be considered preventative in the early post-transplant period since concerns regarding hyperkalemia are minimal[76,77]. The cause for hypokalemia often evident from factors like vomiting, diarrhea, or diuretic therapy. If serum K+ is below 2.5 mEq/L and there is severe muscle weakness or ECG changes, then prompt treatment is indicated. Continuous cardiac monitoring is recommended if there are ECG changes linked to hypokalemia, or underlying cardiac conditions that increase arrhythmia risk in the context of hypokalemia[78,79]. Treating the underlying cause of gastrointestinal losses, reducing or discontinuing diuretics, and supplementing dietary potassium intake are some basic measures to be undertaken. Hospital units will typically strictly guide the constitution of IV K+ formulations and their permissible rate of administration.

Potassium replacement: Continued replacement over days is required to address the marked total body potassium deficit, taking care to prevent transient hyperkalemia during repletion. Serum K+ should be quickly raised to a safe level, followed by slower deficit replacement. Although there are no guidelines specific to KTR, the replacement rate should account for the patient’s GFR. For patients with uncontrolled PTDM and hyperkalemia, insulin therapy and fluid replacement should lower serum K+ towards the deficit-appropriate level, and potassium supplementation can begin when the serum K+ is 4.5 mEq/L or lower. For patients presenting with hypokalemia, insulin therapy is delayed until potassium is above 3.3 mEq/L[80,81].

Long-term supplementation: For long-term management, a variety of oral potassium supplements in different dosage strengths are available, with the choice depending upon the presence of metabolic acidosis or hypophosphatemia[81]. Slow-release tablets have better tolerance but carry a low risk of gastrointestinal intolerance especially with microencapsulated preparations[82]. Other options include replacing loop or thiazide diuretics with potassium-sparing diuretics such as amiloride or triamterene, and adding aldosterone antagonists such as spironolactone or eplerenone if renal K+ wasting is present, although careful monitoring is required. Magnesium deficiency is frequently associated with hypokalemia, and if unrecognized can result in refractory hypokalemia. Reduced intracellular magnesium prevents inhibition of ROMK channels, increasing potassium secretion[83]. While magnesium deficiency alone is insufficient to cause hypokalemia, IV or oral supplementation can be considered if hypomagnesemia is noted. Not all transplant programs routinely monitor post-transplant serum magnesium concentrations, but they should be measured if hypokalemia is noted.

Dietary modification: Dietary intervention for hypokalemia may be less effective due to the predominantly potassium phosphate or potassium citrate form in dietary potassium[84]. Increased fruit intake may have limited impact as well since a large consumption would be required[85]. However, providing dietary advice can still be considered as a part of the overall nutrition plan (Table 3), since hypokalemic patients are often undernourished as well. Food literacy and social support are particularly relevant[86]. Unfortunately there have been no clinical trials of dietary intervention in the context of electrolyte management in KTR.

Table 3 Common examples of food sources containing potassium

Potassium content1	
Low	Medium	High	
Apple juice	Grape juice	Orange juice	
Cranberry juice	Grapefruit juice	Prune juice	
Lemon juice	Pineapple juice	Apricots	
Peach nectar	Apple	Banana	
Pear nectar	Cherries	Breadfruit	
Blackberries	Lychees	All dried fruits	
Blueberries	Plum	Guava	
Raspberries	Pear	Honeydew	
Strawberries	Pomelo	Jackfruit	
Asparagus	Starfruit	Kiwi	
Bamboo shoots	Artichoke	Mango	
Broccoli	Beets	Nectarine	
Cabbage	Carrot	Papaya	
Cucumber	Cauliflower	Persimmon	
Eggplant	Corn	Pomegranate	
Beans	Kale	Lentils	
Lettuce	Mustard greens	Mushrooms (cooked)	
Mushrooms (raw)	Peas	Okra	
Onion	Spinach (raw)	Potatoes	
Pepper	Zucchini	Spinach (cooked)	
Radish	Custard	Sweet potato	
Rhubarb	Cream soup	Tomato	
Tofu	Ice cream	Water chestnut (fresh)	
Turnip	Milk	Winter squash	
Water chestnut (canned)	Yogurt	Yam	
1 Specific amounts allowed should be discussed with a transplant dietician as part of an overall management plan.

All KTR should undergo regular laboratory testing that includes serum electrolyte measurement. On example of such a monitoring strategy includes daily testing until hospital discharge, twice weekly to the end of month three, weekly to the end of month six, every two weeks to the end of month nine, monthly to the end of year two, and then once every three months thereafter, with added testing performed as necessary. Some transplant programs monitor patients remotely, so a clear action plan for incidentally detected emergencies should be developed in advance. A brief summary of some common preventative and management strategies for disorders of K+ homeostasis in KTR is provided in Table 4.

Table 4 Common preventive and management strategies for post-transplant hyperkalemia and hypokalemia

	Hyperkalemia	Hypokalemia	
Pre-transplant	Hold ACE inhibitor or ARB	Hold loop and thiazide diuretics, if applicable	
	Add extra session of hemodialysis		
Early post-transplant	Obtain ECG and administer IV calcium gluconate if appropriate	Obtain ECG and administer IV potassium chloride if appropriate	
	Add extra session of hemodialysis	Use high K+ bath for hemodialysis if needed	
	Correct insulin deficiency	Add KCl to replacement fluid	
	Correct metabolic acidosis	Correct metabolic alkalosis	
	Add loop diuretic	Avoid loop diuretic	
	Avoid potassium-sparing diuretics	Add oral potassium supplement	
	Address constipation	Consult dietician	
	Minimize use of heparin		
	Delay introducing sulfa antibiotic		
	Consult dietician		
Late post-transplant	Reduce or hold ACE inhibitor or ARB, potassium-sparing diuretic	Correct underlying cause, e.g., diarrhea	
	Rule out obstruction	Add ACE inhibitor or ARB, potassium sparing diuretic	
	Reduce or hold sulfa antibiotic, or switch to another prophylactic drug for Pneumocystis jirovecii	Add oral potassium supplement	
	Add fludrocortisone	Identify and correct magnesium deficiency	
	Correct metabolic acidosis	Consult dietician	
	Optimize glycemic control		
	Add oral patiromer or sodium zircomium cyclosilicate		
	Consult dietician		
ACE: Angiotensin-converting enzyme; ARB: Angiotensin II receptor blockers; ECG: Electrocardiogram.

CONCLUSION

Both hyperkalemia and hypokalemia are important electrolyte disturbances encountered when managing KTR, and can present either as medical emergencies or chronic outpatient abnormalities. Experience from the general population and patients with CKD in native kidneys is typically extrapolated to pathophysiology in the transplant kidney and thereby to KTR. Although commonly of multifactorial etiology, ascertaining the specific cause in a particular patient will help guide successful management. Regular monitoring through laboratory testing is essential to detect serious disturbances in K+ metabolism since patients are often asymptomatic. Transcellular shifting, potassium removal or supplementation, and longer-term measures including adjusting immunosuppressive and non-immunosuppressive medications as well as dietary counseling all play a role in ensuring optimal post-transplant patient outcomes.

Conflict-of-interest statement: The authors have no conflict of interest to declare in relation to the manuscript.

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Transplantation

Country of origin: Canada

Peer-review report’s classification

Scientific Quality: Grade B, Grade C

Novelty: Grade B, Grade B

Creativity or Innovation: Grade B, Grade B

Scientific Significance: Grade B, Grade C

P-Reviewer: Cabezuelo AS; Varama A S-Editor: Liu H L-Editor: A P-Editor: Zhang L
==== Refs
1 Wolfe RA Ashby VB Milford EL Ojo AO Ettenger RE Agodoa LY Held PJ Port FK Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant N Engl J Med 1999 341 1725 1730 10580071
2 Tonelli M Wiebe N Knoll G Bello A Browne S Jadhav D Klarenbach S Gill J Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes Am J Transplant 2011 11 2093 2109 21883901
3 Jones JW Gruessner RW Gores PF Matas AJ Hypoaldosteronemic hyporeninemic hyperkalemia after renal transplantation Transplantation 1993 56 1013 1015 8212180
4 Kaplan B Wang Z Abecassis MM Fryer JP Stuart FP Kaufman DB Frequency of hyperkalemia in recipients of simultaneous pancreas and kidney transplants with bladder drainage Transplantation 1996 62 1174 1175 8900321
5 Alfonzo AV Isles C Geddes C Deighan C Potassium disorders--clinical spectrum and emergency management Resuscitation 2006 70 10 25 16600469
6 Rizk JG Lazo JG Jr Quan D Gabardi S Rizk Y Streja E Kovesdy CP Kalantar-Zadeh K Mechanisms and management of drug-induced hyperkalemia in kidney transplant patients Rev Endocr Metab Disord 2021 22 1157 1170 34292479
7 Palmer BF Regulation of Potassium Homeostasis Clin J Am Soc Nephrol 2015 10 1050 1060 24721891
8 Lugo-Baruqui JA Ayyathurai R Sriram A Pragatheeshwar KD Use of Mannitol for Ischemia Reperfusion Injury in Kidney Transplant and Partial Nephrectomies-Review of Literature Curr Urol Rep 2019 20 6 30685826
9 Reiterer C Hu K Sljivic S Falkner von Sonnenburg M Fleischmann E Kainz A Kabon B Mannitol and renal graft injury in patients undergoing deceased donor renal transplantation - a randomized controlled clinical trial BMC Nephrol 2020 21 307 32723374
10 Sharma J Salhotra R Mannitol-induced intraoperative hyperkalemia, a little-known clinical entity J Anaesthesiol Clin Pharmacol 2012 28 546 547 23225957
11 Zheng H Cao X Gao F Li X Wan L Luo A Hyperkalemic cardiac arrest induced by mannitol administration during craniotomy: A case report and review of the literature Front Surg 2022 9 1019101 36303859
12 Laar SCV Schouten GN IJzermans JNM Minnee RC Effect of Mannitol on Kidney Function After Kidney Transplantation: A Systematic Review and Meta-Analysis Transplant Proc 2021 53 2122 2132 34412911
13 Lauzurica R Teixidó J Serra A Torguet P Bonet J Bonal J Borrás M Romero R Caralps A Hydration and mannitol reduce the need for dialysis in cadaveric kidney transplant recipients treated with CyA Transplant Proc 1992 24 46 47 1539337
14 Palmer BF A physiologic-based approach to the evaluation of a patient with hyperkalemia Am J Kidney Dis 2010 56 387 393 20493606
15 Keven K Ozturk R Sengul S Kutlay S Ergun I Erturk S Erbay B Renal tubular acidosis after kidney transplantation--incidence, risk factors and clinical implications Nephrol Dial Transplant 2007 22 906 910 17210594
16 Rosenbaum R Hoffsten PE Cryer P Klahr S Hyperkalemia after renal transplantation. Occurrence in a patient with insulin-dependent diabetes Arch Intern Med 1978 138 1270 1272 354542
17 Velázquez H Perazella MA Wright FS Ellison DH Renal mechanism of trimethoprim-induced hyperkalemia Ann Intern Med 1993 119 296 301 8328738
18 Kleyman TR Roberts C Ling BN A mechanism for pentamidine-induced hyperkalemia: inhibition of distal nephron sodium transport Ann Intern Med 1995 122 103 106 7992983
19 Hiremath S Fergusson DA Fergusson N Bennett A Knoll GA Renin-Angiotensin System Blockade and Long-term Clinical Outcomes in Kidney Transplant Recipients: A Meta-analysis of Randomized Controlled Trials Am J Kidney Dis 2017 69 78 86 27712852
20 Mitterbauer C Heinze G Kainz A Kramar R Hörl WH Oberbauer R ACE-inhibitor or AT2-antagonist therapy of renal transplant recipients is associated with an increase in serum potassium concentrations Nephrol Dial Transplant 2008 23 1742 1746 18234845
21 Oster JR Singer I Fishman LM Heparin-induced aldosterone suppression and hyperkalemia Am J Med 1995 98 575 586 7778574
22 Amdetsion GY Gudeta A Lumley G Sagoo H Aliledhin E Heparin-induced hyperkalemia, can LMWH cause hyperkalemia? A systematic review EJHaem 2023 4 1110 1116 38024642
23 McCauley J Murray J Jordan M Scantlebury V Vivas C Shapiro R Labetalol-induced hyperkalemia in renal transplant recipients Am J Nephrol 2002 22 347 351 12169866
24 Pirsch JD Miller J Deierhoi MH Vincenti F Filo RS A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group Transplantation 1997 63 977 983 9112351
25 Higgins R Ramaiyan K Dasgupta T Kanji H Fletcher S Lam F Kashi H Hyponatraemia and hyperkalaemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Further evidence for differences between cyclosporin and tacrolimus nephrotoxicities Nephrol Dial Transplant 2004 19 444 450 14736972
26 Hoorn EJ Walsh SB McCormick JA Fürstenberg A Yang CL Roeschel T Paliege A Howie AJ Conley J Bachmann S Unwin RJ Ellison DH The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension Nat Med 2011 17 1304 1309 21963515
27 Ishizawa K Wang Q Li J Yamazaki O Tamura Y Fujigaki Y Uchida S Lifton RP Shibata S Calcineurin dephosphorylates Kelch-like 3, reversing phosphorylation by angiotensin II and regulating renal electrolyte handling Proc Natl Acad Sci U S A 2019 116 3155 3160 30718414
28 Heering PJ Kurschat C Vo DT Klein-Vehne N Fehsel K Ivens K Aldosterone resistance in kidney transplantation is in part induced by a down-regulation of mineralocorticoid receptor expression Clin Transplant 2004 18 186 192 15016134
29 Deppe CE Heering PJ Viengchareun S Grabensee B Farman N Lombès M Cyclosporine a and FK506 inhibit transcriptional activity of the human mineralocorticoid receptor: a cell-based model to investigate partial aldosterone resistance in kidney transplantation Endocrinology 2002 143 1932 1941 11956176
30 Olyaei AJ de Mattos AM Bennett WM Immunosuppressant-induced nephropathy: pathophysiology, incidence and management Drug Saf 1999 21 471 488 10612271
31 Remuzzi G Perico N Cyclosporine-induced renal dysfunction in experimental animals and humans Kidney Int Suppl 1995 52 S70 S74 8587288
32 Batlle DC Arruda JA Kurtzman NA Hyperkalemic distal renal tubular acidosis associated with obstructive uropathy N Engl J Med 1981 304 373 380 7453754
33 Thomsen RW Nicolaisen SK Hasvold P Sanchez RG Pedersen L Adelborg K Egstrup K Egfjord M Sørensen HT Elevated potassium levels in patients with chronic kidney disease: occurrence, risk factors and clinical outcomes-a Danish population-based cohort study Nephrol Dial Transplant 2018 33 1610 1620 29177463
34 Meng QH Wagar EA Pseudohyperkalemia: A new twist on an old phenomenon Crit Rev Clin Lab Sci 2015 52 45 55 25319088
35 Teymouri N Mesbah S Navabian SMH Shekouh D Najafabadi MM Norouzkhani N Poudineh M Qadirifard MS Mehrtabar S Deravi N ECG frequency changes in potassium disorders: a narrative review Am J Cardiovasc Dis 2022 12 112 124 35873184
36 Webster A Brady W Morris F Recognising signs of danger: ECG changes resulting from an abnormal serum potassium concentration Emerg Med J 2002 19 74 77 11777886
37 Gasparini A Evans M Barany P Xu H Jernberg T Ärnlöv J Lund LH Carrero JJ Plasma potassium ranges associated with mortality across stages of chronic kidney disease: the Stockholm CREAtinine Measurements (SCREAM) project Nephrol Dial Transplant 2019 34 1534 1541 30085251
38 Moussavi K Fitter S Gabrielson SW Koyfman A Long B Management of Hyperkalemia With Insulin and Glucose: Pearls for the Emergency Clinician J Emerg Med 2019 57 36 42 31084947
39 Mahoney BA Smith WA Lo DS Tsoi K Tonelli M Clase CM Emergency interventions for hyperkalaemia Cochrane Database Syst Rev 2005 2005 CD003235 15846652
40 de Vries BCS Berger SP Bakker SJL de Borst MH de Jong MFC Pre-Transplant Plasma Potassium as a Potential Risk Factor for the Need of Early Hyperkalaemia Treatment after Kidney Transplantation: A Cohort Study Nephron 2021 145 63 70 33212442
41 Gutzwiller JP Schneditz D Huber AR Schindler C Garbani E Zehnder CE Increasing blood flow increases kt/V(urea) and potassium removal but fails to improve phosphate removal Clin Nephrol 2003 59 130 136 12608556
42 Batterink J Cessford TA Taylor RA Pharmacological interventions for the acute management of hyperkalaemia in adults Cochrane Database Syst Rev 2015 10 CD010344 35658162
43 Allon M Shanklin N Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol Am J Kidney Dis 1996 28 508 514 8840939
44 Blumberg A Weidmann P Shaw S Gnädinger M Effect of various therapeutic approaches on plasma potassium and major regulating factors in terminal renal failure Am J Med 1988 85 507 512 3052050
45 Taber DJ Srinivas TM Pilch NA Meadows HB Fleming JN McGillicuddy JW Bratton CF Thomas B Chavin KD Baliga PK Egede LE Are thiazide diuretics safe and effective antihypertensive therapy in kidney transplant recipients? Am J Nephrol 2013 38 285 291 24061145
46 Gama RM Makanjuola D Wahba M Quan V Phanish M Fludrocortisone Is an Effective Treatment for Hyperkalaemic Metabolic Acidosis in Kidney Transplant Recipients on Tacrolimus: A Case Series Nephron 2022 146 190 196 34784594
47 Marfo K Glicklich D Fludrocortisone therapy in renal transplant recipients with persistent hyperkalemia Case Rep Transplant 2012 2012 586859 23259135
48 Sivakumar V Sriramnaveen P Krishna C Manjusha Y Reddy YS Sridhar N Subramanian S Role of fludrocortisone in the management of tacrolimus-induced hyperkalemia in a renal transplant recipient Saudi J Kidney Dis Transpl 2014 25 149 151 24434399
49 Noel JA Bota SE Petrcich W Garg AX Carrero JJ Harel Z Tangri N Clark EG Komenda P Sood MM Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age JAMA Intern Med 2019 179 1025 1033 31180477
50 Schnelle K Winters H Pesavento T Singh P Largest Experience of Safety and Efficacy of Patiromer in Solid Organ Transplant Transplant Direct 2020 6 e595 32851128
51 Shockey W Wiegel JJ Parajuli S Garg N Swanson KJ Mandelbrot DA Potassium-lowering effects of sodium zirconium cyclosilicate in the early post-transplant period Clin Transplant 2024 38 e15156 37812572
52 Sullivan E Ruegger M Dunne I Sutaria N Towers WF Comparison of effectiveness and safety of sodium polystyrene sulfonate and sodium zirconium cyclosilicate for treatment of hyperkalemia in hospitalized patients Am J Health Syst Pharm 2023 80 1238 1246 37335862
53 Winstead RJ Demehin M Yakubu I Song C Brown A Levy M Gupta G Sodium zirconium cyclosilicate use in solid organ transplant recipients and its effect on potassium and immunosuppression Clin Transplant 2020 34 e13791 31991491
54 Perazella MA Mahnensmith RL Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose Clin Nephrol 1996 46 187 192 8879854
55 Prasad GVR Beckley J Mathur M Gunasekaran M Nash MM Rapi L Huang M Zaltzman JS Safety and efficacy of prophylaxis for Pneumocystis jirovecii pneumonia involving trimethoprim-sulfamethoxazole dose reduction in kidney transplantation BMC Infect Dis 2019 19 311 30953458
56 MacDonald AS RAPAMUNE Global Study Group A worldwide, phase III, randomized, controlled, safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allografts Transplantation 2001 71 271 280 11213073
57 Johnson RW Kreis H Oberbauer R Brattström C Claesson K Eris J Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure Transplantation 2001 72 777 786 11571437
58 Chapman WC Brown RS Jr Chavin KD Sudan D Koneru B Junge G Dong G Patel D Teperman L Fung JJ Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients: 24-Month Results for the North American Subpopulation Transplantation 2017 101 341 349 28121741
59 Rostaing L Massari P Garcia VD Mancilla-Urrea E Nainan G del Carmen Rial M Steinberg S Vincenti F Shi R Di Russo G Thomas D Grinyó J Switching from calcineurin inhibitor-based regimens to a belatacept-based regimen in renal transplant recipients: a randomized phase II study Clin J Am Soc Nephrol 2011 6 430 439 21051752
60 Gupta G Regmi A Kumar D Posner S Posner MP Sharma A Cotterell A Bhati CS Kimball P Massey HD King AL Safe Conversion From Tacrolimus to Belatacept in High Immunologic Risk Kidney Transplant Recipients With Allograft Dysfunction Am J Transplant 2015 15 2726 2731 25988397
61 Duni A Koutlas V Tsitouridis A Tzalavra E Oikonomaki T Kitsos A Rapsomanikis KP Alekos J Tatsis V Pappas C Mitsis M Dounousi E Longitudinal Assessment of Electrolyte Disorders in a Cohort of Chronic Stable Kidney Transplant Recipients Transplant Proc 2021 53 2786 2792 34690001
62 SQUIRES RD HUTH EJ Experimental potassium depletion in normal human subjects. I. Relation of ionic intakes to the renal conservation of potassium J Clin Invest 1959 38 1134 1148 13664789
63 Adrogué HJ Lederer ED Suki WN Eknoyan G Determinants of plasma potassium levels in diabetic ketoacidosis Medicine (Baltimore) 1986 65 163 172 3084904
64 Bradberry SM Vale JA Disturbances of potassium homeostasis in poisoning J Toxicol Clin Toxicol 1995 33 295 310 7629896
65 Fuentebella J Kerner JA Refeeding syndrome Pediatr Clin North Am 2009 56 1201 1210 19931071
66 Brown MJ Brown DC Murphy MB Hypokalemia from beta2-receptor stimulation by circulating epinephrine N Engl J Med 1983 309 1414 1419 6314140
67 Williams ME Gervino EV Rosa RM Landsberg L Young JB Silva P Epstein FH Catecholamine modulation of rapid potassium shifts during exercise N Engl J Med 1985 312 823 827 2858053
68 Young DB Quantitative analysis of aldosterone's role in potassium regulation Am J Physiol 1988 255 F811 F822 3056039
69 Morales JM Andrés A Dominguez-Gil B Sierra MP Arenas J Delgado M Casal MC Rodicio L Tubular function in patients with hypokalemia induced by sirolimus after renal transplantation Transplant Proc 2003 35 154S 156S 12742489
70 Büchler M Caillard S Barbier S Thervet E Toupance O Mazouz H Hurault de Ligny B Le Meur Y Thierry A Villemain F Heng AE Moulin B Morin MP Noël C Lebranchu Y SPIESSER Group Sirolimus versus cyclosporine in kidney recipients receiving thymoglobulin, mycophenolate mofetil and a 6-month course of steroids Am J Transplant 2007 7 2522 2531 17868057
71 Liu J Liu D Li J Zhu L Zhang C Lei K Xu Q You R Efficacy and Safety of Everolimus for Maintenance Immunosuppression of Kidney Transplantation: A Meta-Analysis of Randomized Controlled Trials PLoS One 2017 12 e0170246 28107397
72 Sundaram V Abraham G Sundaram V Mathew M Bhaskar S Ponnusamy J Prabu S Rapamycin-induced hypokalaemic nephropathy in a middle-aged hypertensive male Nephrol Dial Transplant 2007 22 1798 17347279
73 Vlahovic G Meadows KL Uronis HE Morse MA Blobe GC Riedel RF Zafar SY Alvarez-Secord A Gockerman J Starodub AN Ready NE Anderson EL Bendell JC Hurwitz HI A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors Cancer Chemother Pharmacol 2012 70 95 102 22638798
74 Shiina Y Kobayashi A Yamamoto I Koda N Miyazawa K Kawabe M Sugano N Urabe F Miki J Yamada H Kimura T Maruyama Y Tanno Y Ohkido I Yamamoto H Yokoo T A Case of Hypokalemia Caused by Left Native Renal Artery Stenosis in a Kidney Transplant Recipient Nephron 2023 147 Suppl 1 46 52 36940677
75 Fujimoto K Hisanaga S Kuroda S Kodama K Sugiyama F Kikuchi M Kita T Yamashita A Nagai T Kamimura T Kaikita K Imamura T Fujimoto S A case of primary aldosteronism with excessive secretion of renin that was unmasked by kidney transplantation CEN Case Rep 2024 13 1 8 37010722
76 Medeiros H Lima PH Junior VS Souza DA Pinheiro AM Martins RR A H Costa KM Junior JHD Medeiros PJ Da Silva WA Sr A Comparison Between Saline and Balanced Solutions in Kidney Transplants: A Randomized Clinical Trial Cureus 2023 15 e49813 38164322
77 O'Malley CMN Frumento RJ Hardy MA Benvenisty AI Brentjens TE Mercer JS Bennett-Guerrero E A randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl during renal transplantation Anesth Analg 2005 100 1518 1524 15845718
78 Chen EH Hollander JE When do patients need admission to a telemetry bed? J Emerg Med 2007 33 53 60 17630076
79 Drew BJ Califf RM Funk M Kaufman ES Krucoff MW Laks MM Macfarlane PW Sommargren C Swiryn S Van Hare GF American Heart Association Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young Practice standards for electrocardiographic monitoring in hospital settings: an American Heart Association scientific statement from the Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Computerized Electrocardiology and the American Association of Critical-Care Nurses Circulation 2004 110 2721 2746 15505110
80 Crop MJ Hoorn EJ Lindemans J Zietse R Hypokalaemia and subsequent hyperkalaemia in hospitalized patients Nephrol Dial Transplant 2007 22 3471 3477 17848395
81 Kim GH Han JS Therapeutic approach to hypokalemia Nephron 2002 92 Suppl 1 28 32 12401935
82 Blanchard A Bockenhauer D Bolignano D Calò LA Cosyns E Devuyst O Ellison DH Karet Frankl FE Knoers NV Konrad M Lin SH Vargas-Poussou R Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference Kidney Int 2017 91 24 33 28003083
83 Huang CL Kuo E Mechanism of hypokalemia in magnesium deficiency J Am Soc Nephrol 2007 18 2649 2652 17804670
84 Kassirer JP Berkman PM Lawrenz DR Schwaartz WB The critical role of chloride in correcting hypokalemic alkalosis in man Am J Med 1965 38 172 189 14256714
85 Kopyt N Dalal F Narins RG Renal retention of potassium in fruit N Engl J Med 1985 313 582 583
86 Boslooper-Meulenbelt K Patijn O Battjes-Fries MCE Haisma H Pot GK Navis GJ Barriers and Facilitators of Fruit and Vegetable Consumption in Renal Transplant Recipients, Family Members and Healthcare Professionals-A Focus Group Study Nutrients 2019 11
