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What is the plasma potassium conc. controlled at? Why is this balance important? What are four physiological systems involved in maintaining this balance? Describe how a couple of them work including time frame.

The plasma potassium concentration is tightly controlled over the physiologic range of 3.5-5.5 mEq/L. The extracellular potassium concentration is vital to a variety of basic cell functions, including cell excitability and nerve conduction. For example, alterations in the plasma potassium concentration by as little as 1 mEq/L can precipitate disturbances in nerve conduction resulting in muscular paralysis, cardiac conduction abnormalities, and death. The prevailing plasma potassium concentration is dependent on potassium balance as depicted in Eq. (11.1).
[]KKKinputoutput+++=− (11.1)
The concept of potassium balance (input versus output) provides a useful paradigm to assess changes in the plasma potassium concentration. Four systems participate in a potassium balance framework (Fig. 11.1):
• Diffusion or transport of potassium between body fluid compartments, specifically the extracellular and intracellular compartment (referred to as internal balance).
• Renal elimination of potassium (see Fig. 8.5).
• Dietary consumption (the potassium intake in a healthy adult varies between 80 and 150 mEq/d). Dietary intake of potassium is not consciously regulated, but depends on the composition of the diet and mass consumption.
• Insensible losses from the skin and gastrointestinal tract. Potassium lost from these sites is difficult to measure, but relatively small, unless there is a concomitant clinical condition (diarrhea).

Cell redistribution is an essential acute mechanism that quickly offsets an increase in the serum concentration of potassium following an oral or intravenous load. Changes in the serum potassium concentration are attenuated within minutes via cellular uptake.

Renal elimination of a potassium load requires several days to achieve maximal effect, since protein synthesis (ion channels, aldosterone) is involved in mediating this effect. Aldosterone is an important factor involved in regulating renal elimination of potassium; therefore, changes in the circulating level of aldosterone are commonly implicated in the pathogenesis of abnormal potassium homeostasis.


What causes potassium to enter into cells? What happens during exercise? After a large intake of potassium? How do acid base disturbances affect potassium influx/efflux in cells? What care must be taken when treating an acid/base disorder?

Several systems regulate the distribution of potassium between the intracellular and extracellular compartments. Insulin and b-adrenergic agonists stimulate potassium uptake into cells by activating cellular Na/K-ATPase (Fig. 11.2). These systems exert their effect rapidly, usually within minutes. For example, within 30 minutes of an exogenous potassium load, approximately 70% of the load has been buffered via cellular uptake. Redistribution of potassium prevents a potentially life-threatening increase in extracellular potassium concentration.

Exercising or damaged muscle releases large quantities (perhaps 100-200 mEq) of potassium into the extracellular compartment. Fortuitously these states are also characterized by endogenous release of epinephrine, which stimulates the Na/K-ATPase and, thereby, promotes potassium movement into the cellular compartment. This response prevents critical changes in the serum potassium concentration. An endogenous dietary load of potassium stimulates pancreatic release of insulin, which, in turn, buffers the increase in serum potassium by shifting potassium into cells.

Acid-base disturbances also alter the cellular distribution of potassium, although, the effect is less predictable than previously thought. Acidosis (decreased extracellular hydrogen ion concentration) shifts potassium into the extracellular space in exchange for hydrogen ions, which are buffered by intracellular proteins (see Fig. 11.2). The converse is true in alkalosis. An organic acidosis (lactic acidosis and ketoacidosis) elicits a relatively smaller change in potassium concentration, compared to an acidosis resulting from an inorganic acid (diarrhea).

The potassium concentration must be monitored carefully during the treatment of an acid-base disorder. For example, as insulin is administered to treat diabetic ketoacidosis, the potassium concentration will decrease for two reasons: (1) insulin directly promotes movement of potassium into cells, and (2) correction of the acidosis indirectly promotes potassium entry into cells, by decreasing the extracellular hydrogen ion concentration.


How is the excretion of potassium regulated? Which form of excretion is regulated? Where does this regulation occur and how?

Although, cellular redistribution of potassium is a vital acute mechanism to buffer a potassium load, excess potassium must ultimately be eliminated from the body. Insensible losses of potassium (stool, sweat) are not actively regulated. Conversely, renal elimination of potassium is actively controlled by the plasma concentration of aldosterone and potassium. The fraction of filtered potassium excreted each day varies from 200%. Much of these data have been derived from renal micropuncture studies performed in accessible portions of the nephron (Fig. 11.3). These studies reveal that potassium reabsorption occurs throughout the proximal tubule, loop of Henle, and inner medullary collecting duct, while potassium secretion occurs in the late distal convoluted tubule and cortical collecting duct. Variations in dietary intake of potassium have little effect on proximal tubular and loop of Henle reabsorption. Conversely, potassium secretion varies widely in the late distal tubule and cortical collecting duct depending on the dietary intake.


What % of K is reabsorbed in the PT? How? What % of K is reabsorbed in the mTAL? How? Where else is potassium reabsorbed? Summarize potassium reabsorption/secretion in the kidney.

The proximal convoluted tubule reabsorbs 70%-80% of the filtered potassium, largely via passive paracellular diffusion. A small electrochemical gradient favors potassium reabsorption, however, the vast majority of potassium reabsorption occurs via passive entrainment in water (solvent drag).

15%-20% of the filtered potassium is reabsorbed in the medullary thick ascending limb of Henle (mTAL). The pathways involved in potassium transport include NKCC2 and paracellular diffusion secondary to the positive transepithelial potential generated at this site. However, the mTAL does not directly regulate potassium transport in response to variations in potassium intake or serum concentration.

Potassium reabsorption has been described in the medullary collecting duct (see Fig. 11.4). This pathway plays an important role in clinical conditions associated with potassium depletion.

In summary, 70%-90% of the filtered potassium is reabsorbed in the proximal tubule and loop of Henle, irrespective of the dietary intake. Reducing the dietary intake of potassium inhibits potassium secretion in the cortical collecting duct, while promoting its reabsorption in the medullary collecting duct. In contrast, consumption of diets enriched with potassium increases potassium secretion in the cortical collecting duct (Fig. 11.4). Several factors (aldosterone, dietary potassium, urine flow, and urine sodium) are involved in modulating potassium excretion.


How is K secreted and where? What are 3 things that modulate sodium excretion? What are some mechanisms by which they do it?

The cortical collecting duct principal cells secrete potassium into the urine (see Fig. 8.5). Potassium secretion is modulated by urine flow rate, sodium delivery, circulating aldosterone, and potassium itself. Aldosterone stimulates the Na/K-ATPase and, therefore, raises the intracellular concentration of potassium. In addition, aldosterone increases the open probability state of ROMK. Aldosterone stimulates sodium reabsorption (via ENaC), which increases the electrochemical gradient for potassium secretion. Collectively, these actions promote potassium secretion in the distal nephron.
In addition, sodium delivery and urine flow rate exert powerful effects on potassium secretion. Increased urine flow carries secreted potassium downstream, which, in turn, maintains a favorable chemical gradient for potassium secretion. Sodium delivery to the cortical collecting duct increases the transepithelial potential, which accelerates potassium secretion via a favorable electrical gradient.
Finally, potassium itself is a central regulator of potassium homeostasis via a classic feedback system and a recently characterized feedforward system. It is well established that an increase in plasma potassium concentration increases the activity of the Na/K-ATPase and promotes aldosterone release. Both actions increase urine potassium secretion and return the serum concentration to normal. This feedback system is robust but is intrinsically slow and requires a system perturbation to evoke. Recent studies have revealed that diets enriched with potassium are not associated with significant changes in the plasma concentration of potassium or aldosterone, but are accompanied by an increase in renal elimination of potassium. It now appears that dietary potassium is sensed in the gastrointestinal tract (by an unknown mechanism) resulting in renal potassium excretion. This system (referred to as feedforward control) permits swift control of the serum potassium concentration. Acting in concert with feedback control, these systems provide robustness, accuracy, and speed in the regulation of the extracellular concentration of potassium.


Describe 3 mechanisms that lead to hypokalemia with diuretic use.

Diuretics are commonly employed to increase the urinary excretion of sodium and water. This is useful in the management of edema that complicates some clinical conditions such as congestive heart failure. However, these agents produce hypokalemia. Several mechanisms contribute to this effect, including: (1) increased urine flow to the collecting duct, (2) volume contraction with an attendant rise in circulating aldosterone, and (3) augmentation of the negative transepithelial potential via increased delivery of sodium to the cortical collecting duct (CCD).


What are 4 categories of disorders of potassium homeostasis? What are some good first steps at identifying a specific disorder?

Disorders of potassium homeostasis can be classified into four categories according to a balance model that highlights potassium input versus output (see Eq. [11.1]). These categories include:

1. Increased or decreased intake
2. Altered cellular distribution
3. Increased insensible losses (stool, sweat)
4. Changes in renal elimination

Calculation of the renal contribution to potassium excretion is a useful clinical tool to differentiate renal from extrarenal disturbances associated with potassium disorders. Subclassification of the potassium disorders using this paradigm is remarkably practical. For example, the extrarenal disturbances primarily include altered dietary intake, cellular redistribution, or gastrointestinal losses. Conversely, disturbances in renal elimination usually involve changes in the bioactivity of aldosterone (i.e., decreased aldosterone synthesis or resistance).
Therefore, a reasonable initial step in the evaluation of potassium disorders is determination of the renal excretion of potassium. The 24-hour urine potassium is the gold standard to assess the renal handling of potassium. However, the 24-hour calculation is inconvenient since it requires a complete collection of urine during a 24-hour period and necessarily delays the diagnosis.


What is TTKG? How is calculated? What is it used to calculate? What are some things to keep in mind when using it?

Recently, the transtubular potassium gradient (TTKG) has supplanted the 24-hour collection in the initial evaluation of potassium disorders. The TTKG has proven to be both convenient and clinically reliable. The TTKG the ratio of potassium concentration at the end the cortical collecting duct to the plasma potassium concentration (Fig. 11.5). Therefore, it is a semiquantitative reflection of the driving force for potassium secretion in the kidney. Normally, the TTKG is elevated in hyperkalemic states and reduced in hypokalemic states. An abnormal TTKG implies deranged renal elimination of potassium.
The TTKG is easily measured at the bedside, using simple urine and plasma chemistries (Eq. [11.2]):


The calculation is based on the premise that a reasonable approximation of the potassium concentration in the terminal cortical collecting duct can be calculated by adjusting for water reabsorption in the medullary collecting duct. Several caveats apply to calculation of the TTKG, as summarized below:
• A relatively minor fraction of the urine potassium is derived from secretion in the medullary collecting duct (a reasonable, but, imprecise assumption).
• A relatively minor fraction of the filtered load of potassium is reabsorbed in the medullary collecting duct
(a reasonable, but, imprecise assumption).
• The urine osmolality must exceed the plasma osmolality. This is an absolute requirement for accuracy.
• The TTKG is less reliable in the evaluation of
hypokalemia than hyperkalemia.


What TTKG and 24 hour urine collection values constitute the accepted threshold for an appropriate renal response to hypokalemia? What are 3 general categories of extrarenal etiology of hypokalemia?

The normal physiologic response to potassium depletion is conservation of potassium. Suppression of aldosterone and increased expression of H/K-ATPase in the medullary collecting duct promote net reabsorption of potassium. Therefore, a TTKG of


How can decreased intake lead to hypokalemia? Why is it rare?

Decreased intake alone is a rare cause of hypokalemia, since the kidney can reduce the urinary excretion of potassium to <10 mEq/d. An unusual, but recognized, cause of hypokalemia involves the ingestion of nonnutritive compounds (pica) that impair oral absorption of potassium (clay ingestion or geophagia). Therefore, a comprehensive dietary history should be sought in all patients with hypokalemia.


Describe how cellular redistribution can lead to hypokalemia including various etiologies. Describe a genetic illness that causes it. List a systemic disorder that can mimic this genetic illness.

Cellular redistribution can be deduced from an understanding of the physiologic variables known to affect cellular uptake of potassium (see Figs. 11.2 and 11.3). An increase in extracellular pH is associated with a shift of potassium into cells as hydrogen ions move down their concentration gradient from the intracellular to extracellular compartment. Administration of insulin or carbohydrate stimulates the uptake of potassium into cells via Na/K-ATPase. Therefore, the treatment of diabetes mellitus is associated with a decrease in serum potassium concentration. Clinical conditions that require treatment with a b-adrenergic agonist (asthma, acute bronchitis) have been associated with a decrease in plasma potassium concentration of up to 1 mEq/L. An acute increase in hematopoietic cell production (treatment of megaloblastic anemia with vitamin B12 or folate) can lower the serum potassium since new cell synthesis requires considerable potassium. Hypokalemic periodic paralysis is a rare disorder, which can be acquired or genetic. It is associated with sudden movement of potassium into cells and severe hypokalemia; complicated by muscular weakness, paralysis, and occasionally death. The genetic basis of hypokalemic periodic paralysis involves loss-of-function mutations in voltage gated calcium, sodium, or potassium channels. How this leads to increased cellular uptake of potassium is poorly understood. Hyperthyroidism has also been associated with a syndrome that mimics hypokalemic periodic paralysis, although the mechanism is not known. Treatment of the hyperthyroidism leads to resolution of the syndrome.


Describe GI K+ loss.

Lower gastrointestinal fluid loss is frequently complicated by hypokalemia, since stool water contains 40-80 mEq/L of potassium. Upper gastrointestinal fluid loss is also associated with hypokalemia, although analysis of water from the upper gastrointestinal tract reveals <10 mEq/L of potassium. Therefore, the mechanism of hypokalemia in vomiting involves excessive renal excretion of potassium rather than direct losses (see Fig 14-7).


What are two categories of etiologies of renal potassium deficit? What is this caused? What TTKG value indicates this?

A TTKG of >3 in the setting of hypokalemia indicate that the kidney is responsible for the potassium deficit (renal leak). The physiology of renal potassium loss can be inferred from an understanding of the factors involved in mediating renal potassium secretion. Assessment of the blood pressure and arterial pH provide valuable information to establish the specific clinical disease responsible for a renal leak (Fig. 11.8).

High Blood pressure and hypokalemia + TTKG>3
Normal BP and hypokalemia + TTKG >3


What are 4 etiologies of hypokalemia characterized by high bp?


Less common causes of hypertension and increased renal secretion of potassium include Cushing syndrome, congenital adrenal hyperplasia (CAH), syndrome of apparent mineralocorticoid excess (AME), and Liddle syndrome


Explain primary and secondary aldosteronism.

Hypertension and hypokalemia suggests primary or secondary hyperaldosteronism. Primary hyperaldosteronism is usually associated with an adrenal tumor producing excess aldosterone or adrenal hyperplasia. Hyperaldosteronism facilitates sodium reabsorption, which causes hypertension and volume expansion. A metabolic alkalosis is also common in this setting since aldosterone promotes acid excretion in the urine. Secondary hyperaldosteronism is usually caused by renal artery stenosis (RAS). RAS decreases renal perfusion pressure, which, in turn, increases renin secretion from the afferent arteriole. Renin catalyzes the conversion of angiotensinogen to angiotensin I. Converting-enzyme converts angiotensin I to angiotensin II, which stimulates aldosterone synthesis. Primary hyperaldosteronism can be differentiated from RAS by measuring the plasma renin. The volume expansion associated with primary hyperaldosteronism suppresses renin, compared to RAS.


What are some etiologies of hypokalemia with normal or low BP? What is an important test to distinguish them? What do the results of this test point to?

In the absence of hypertension, measurement of the systemic pH is indispensible. A metabolic acidosis suggests a diagnosis of renal tubular acidosis (RTA). The mechanism of hypokalemia in the RTAs is not well understood, however, some RTAs are characterized by mild volume contraction, which increases the plasma aldosterone. A metabolic alkalosis is consistent with a diagnosis of vomiting, diuretic use, Bartter or Gitelman syndrome.


How does vomiting lead to a metabolic alkalosis and hypokalemia?

Loss of upper gastrointestinal fluid (vomiting) alone is unlikely to produce hypokalemia, since the concentration of potassium in the fluid is low (<10 mEq/L). However, vomiting is invariably accompanied by excess renal excretion of potassium because of hyperaldosteronism induced by volume contraction. The loss of gastric hydrochloric acid is responsible for the development of a metabolic alkalosis.


How can diuretics lead to metabolic alkalosis and hypokalemia?

Diuretics are commonly implicated in the development of hypokalemia. Several mechanisms are likely responsible, including, secondary hyperaldosteronism because of volume contraction, increased sodium delivery to the distal nephron, and direct inhibition of potassium reabsorption in the loop of Henle. An important caveat in this setting is that the blood pressure may be elevated, if the diuretics are being used to treat hypertension.


How can Bartter or Gitelmans syndromes lead to metabolic alkalosis and hypokalemia?

Several variants of Bartter syndrome have been previously described (see Fig. 7.3). Regardless of the underlying mutation, Bartter syndrome is associated with impaired NKCC2 (a loop diuretic-like effect). Gitelman syndrome is caused by loss-of-function mutations of NCC, which is equivalent to a thiazide diuretic-like effect. Not surprisingly, both syndromes are associated with hypokalemia and metabolic alkalosis.


How should hypokalemia be treated? What are some possible complications and some guidelines to avoid them?

Since 98% of the potassium is distributed in the intracellular compartment, the serum potassium concentration is an unreliable indicator of the total body potassium deficit. Estimates of the total body potassium deficit using multicompartment models suggest that a serum potassium concentration of 3.0-3.5 mEq/L is associated with a deficit of 100-300 mEq; a concentration of 2.5-3.0 mEq/L is associated with a deficit of 300-600 mEq, and a level <3.0 mEq/L) should be treated without delay. An intravenous preparation, combining potassium chloride with saline, is desirable. Glucose containing solutions should be avoided since the compulsory increase in insulin will promote potassium uptake into cells. The maximal rate of administration of intravenous potassium is 10-20 mEq/h. The risk of hyperkalemia and cardiotoxicity is considerable at rates that exceed this


How is hyperkalemia classified?

The mechanism of hyperkalemia is conceptually analogous to hypokalemia, reflecting an imbalance in potassium input relative to output. Clinically, it is useful to classify the hyperkalemic disorders into extrarenal versus renal causes with a TTKG (see Fig. 11.6).


Describe various etiologies of hyperkalemia? What is pseudohyperkalemia and what causes it?

A healthy kidney can increase urinary excretion to >400 mEq/d, therefore, excessive dietary intake of potassium is an uncommon cause of hyperkalemia, unless accompanied by impaired renal excretion. Fruits and vegetable are rich in potassium and their intake should be monitored carefully in patients with impaired renal function.
Cellular redistribution is a common cause of hyperkalemia (Fig. 11.9). Spurious or pseudohyperkalemia is quite common and should be considered in asymptomatic patients with unexplained hyperkalemia. Pseudohyperkalemia is almost always caused by lysis of red blood cells in a phlebotomy specimen. Other causes include traumatic venipuncture, severe leukocytosis or thrombocytosis (these fragile cells leak potassium during sample preparation), and prolonged storage of the sample. Pseudohyperkalemia can be differentiated from true hyperkalemia by repeating the analysis on a fresh, carefully drawn, atraumatic specimen.
Tissue necrosis (trauma, hemolysis, tumor cell lysis after chemotherapy) liberates potassium into the extracellular space. Metabolic acidosis induces a shift of potassium from the intracellular to extracellular compartment as hydrogen ions are buffered within cells. Thus, the serum potassium must be monitored carefully during the treatment of metabolic acidosis.
Drugs are frequently implicated in the pathogenesis of hyperkalemia. Several agents interfere with cellular uptake of potassium, including digitalis compounds and b-adrenergic antagonists.
Insulin deficiency and hyperglycemia are associated with hyperkalemia. Insulin deficiency necessarily interferes with potassium movement into cells. Hyperglycemia (indeed, hyperosmolality in general) promotes water movement via osmosis from the intracellular to extracellular compartment. This appears to facilitate potassium movement via solvent drag.
Severe exercise has been associated with the development of hyperkalemia. Presumably there is a delay between potassium released during depolarization and reuptake during repolarization. Hyperkalemic periodic paralysis is a rare genetic disorder characterized by episodic weakness and paralysis. The mutation involves a gain-of-function mutation in the alpha subunit of the skeletal muscle sodium channel. How this leads to potassium release from cells is not known. Hyperkalemic periodic paralysis is precipitated by cold exposure, rest after exercise, potassium-rich foods, to name a few.


What are three things that are associated with impaired K+ renal excretion and thus hyperkalemia?

Impaired renal excretion of potassium is associated with one or more of the following (Fig. 11.10):
• Decreased aldosterone action or secretion
• Decreased sodium uptake in the distal nephron
• Decreased kidney function (acute or chronic kidney injury)


Describe various etiologies of hypoaldosteronism.

Medication-induced hyperkalemia impairs renal excretion of potassium by decreasing aldosterone bioactivity. Spiranolactone directly antagonizes the effect of aldosterone on the mineralocorticoid receptor in the distal nephron. Heparin and the nonsteroidal anti-inflammatory agents interfere with the synthesis of aldosterone. Inhibition of the renin-angiotensin system with converting-enzyme inhibitors, angiotensin-receptor blocking agents, or renin inhibitors, all decrease the synthesis of aldosterone. Severe medication-induced hyperkalemia is uncommon in healthy adults, since the increase in potassium concentration directly stimulates potassium secretion in the distal nephron.

Type 1 pseudohypoaldosteronism is caused by loss-of-function mutations in the mineralocorticoid receptor, resulting in aldosterone resistance. Type 2 pseudohypoaldosteronism is complex disorder that is characterized by multiple transport abnormalities, including activation of NCC and reduced ROMK and CCD paracellular chloride transport, which, in turn, decrease potassium and hydrogen ion secretion. Mutations of the WNK kinase family of proteins are involved in this disorder.
Primary adrenal insufficiency (decreased aldosterone synthesis) should be considered in all patients with hyperkalemia.
The syndrome of hyporeninemic hypoaldosteronism is a relatively common cause of hyperkalemia. It is especially prevalent in patients with mild chronic kidney disease and diabetic nephropathy. The mechanism of hyporeninemia is not well understood.


Describe how decreased sodium delivery or reabsorption in the CCD can cause hyperkalemia.

Any condition that decreases the ECV and, accordingly, distal delivery of sodium, can promote hyperkalemia. Sodium reabsorption via ENaC is involved in the generation of the negative transepithelial potential characteristic of the cortical collecting duct. This potential promotes potassium secretion. Amiloride and triamterene inhibit ENaC in the distal nephron and, thereby, reduce potassium secretion.


Describe how kidney disease can lead to hyperkalemia.

Perhaps the most common cause of hyperkalemia involves a combination of increased dietary consumption coupled with decreased kidney function (decreased glomerular filtration rate). Patients with renal disease are generally placed on a potassium-restricted diet to minimize this complication.


What are some symptoms of hyperkalemia? What can be used to identify and type hyperkalemia? Explain.

Hyperkalemia has been associated with virtually every cardiac rhythm disturbance, severe muscular paralysis, and death. Therefore, an increase in the serum potassium concentration requires early evaluation and prompt management. Unfortunately, the severity of hyperkalemia does not correlate with the serum potassium concentration. The electrocardiogram (ECG) has proven useful in determining the severity of hyperkalemia (Fig. 11.11). However, ECG changes are seen in 6.5 mEq/L should also be treated aggressively, regardless of the ECG findings.


How should hyperkalemia be treated? How do these treatments work?

The accepted management of hyperkalemia includes:
• Stabilization of excitable membranes with intravenous calcium.
• Promote cellular uptake of potassium with insulin,
sodium bicarbonate, or b2-adrenergic agonists.
• Promote extrarenal loss of potassium with sodium polystyrene exchange resins or hemodialysis.
• Promote renal loss of potassium with diuretics (assuming normal urine flow).

Recently, the use of sodium bicarbonate has been questioned, since experimental studies have failed to demonstrate predictable decreases in serum potassium (with the possible exception of patients with renal disease and metabolic acidosis).

Acute management of life-threatening hyperkalemia (symptomatic, serum potassium >6.5 mEq/L, or ECG changes) involves the administration of intravenous calcium (Fig. 11.12).

Calcium restores membrane excitability to normal within minutes and lasts for 1 hour. Insulin with dextrose should also be administered. The combination promotes potassium uptake into cells within 15 minutes and lasts 4-6 hours. 10-20 mg of nebulized salbutamol reduces the serum potassium within 1-2 minutes and lasts up to 2 hours. Although transient, these maneuvers lower the potassium by approximately 0.5-1.0 mEq/L each.
The cation exchange resin, Kayexalate, binds potassium in the gastrointestinal tract in exchange for sodium. This agent requires several hours to exert an effect, has questionable efficacy, and has been associated with colonic necrosis. Since it is coadministered with an osmotic laxative, it is unclear which agent is responsible for potassium loss in the stool. Regardless, Kayexalate has an extensive track record in the management of hyperkalemia and remains a popular therapy. Administration of a loop diuretic to promote potassium loss in the urine is a useful approach provided the urine output is normal. Urine flow and potassium concentration should be monitored for efficacy. Finally, hemodialysis rapidly lowers the serum potassium concentration and is the treatment of choice in patients with advanced kidney disease.