Date of publication: May 19, 2016

News & Views

Hyperkalemia in Chronic Disease

Potassium is the most abundant cation in the body, essential for maintaining fluid and electrolyte balance. 98% of potassium is stored in the intracellular space, with only 2% extracellularly.[1] However, this 2% is vital for maintaining the intracellular and extracellular ratio of potassium, and therefore the resting membrane potential, particularly of the myocardium. This leads to the regulation of serum potassium within a narrow range of 3.5-5 mmol/l.[1]

The kidney is responsible for 90% of daily potassium excretion and is therefore essential for maintaining long-term potassium homeostasis and serum potassium levels, with the remaining 10% excreted by the gastrointestinal tract.[1]The hormones insulin and catecholamine are responsible for the short-term response of moving potassium intracellularly and are released when foods containing glucose and potassium are consumed.[1] Disturbances in these homeostatic mechanisms can lead to hyperkalemia with potentially life-threatening consequences.[2]

Elevated potassium levels include can be found in cases of:

  • Pseudohyperkalemia– a false measurement of hyperkalemia due to muscle activation during phlebotomy or lysis of red blood cells in the sample; this should be excluded by a repeat sample[3]
  • NSAID use – NSAIDs reduce renin secretion causing decreased potassium secretion, and so should be used with caution in patients already at risk of hyperkalemia[3]
  • Use of renin-angiotensin-aldosterone system inhibitors– RAAS inhibition affects renal potassium excretion through reducing both the glomerular filtration rate (GFR) and serum aldosterone levels[4]
  • Kidney disease– CKD is the most common cause of hyperkalemia, with potassium excretion reduced primarily due to an impaired GFR, but also through an extracellular shift of potassium caused by metabolic acidosis of renal failure[5]

Hyperkalemia is often asymptomatic until potassium levels exceed 5.5 mmol/l. At this point patients may present with muscle twitching and weakness, changes in ECG and cardiac arrhythmias caused by changes in neuromuscular and cardiac function.[2]

Rates of hyperkalemia in hospitalized patients vary depending on the potassium limit used, from 1.4% to 10%, with one review estimating that hyperkalemia was responsible for 1:1000 deaths.[1] The exact prevalence of hyperkalemia in the community setting is unknown, but is considered to be a common problem.[3]

Patients with chronic kidney disease (CKD) are particularly at risk of hyperkalemia, and the presence of elevated potassium levels increases with CKD stage:[5]

Patient population Rate of hyperkalemia (≥5.5 mmol/l)
No CKD 8.9%
Stage 3 20.7%
Stage 4 42.1%
Stage 5 56.7%

The presence of hyperkalemia is associated with increased mortality, and analysis of CKD patients with serum potassium ≥5.5 mmol/l found that they had a 10-fold increase in mortality rate within 24 hours (see Figure 1).[5]

A further analysis of patients with a range of comorbidities (CKD stages 3-5, heart failure, diabetes, cardiovascular disease and hypertension) reported higher serum potassium levels compared to control groups along with a significant increase in risk of mortality for patients ≥65 yrs compared with 45-64 yrs.[6]

While the potential for hyperkalemia in patients with normal renal function is small, the risk for patients with comorbid conditions such as CKD is increased and potentially life threatening.[2] Potassium levels should be considered when prescribing medications for these patients and any changes carefully monitored.

Figure 1: Odds of Death Within 1 Day of a Hyperkalemic Event, by Potassium Category and Chronic Kidney Disease (CKD)



  1. Rastegar A, Soleimani M. Hypokalaemia and Hyperkalaemia. Postgrad Med J. 2001;77:759-764. doi:10.1136/pmj.77.914.759.
  2. Kraft MD, Btaiche IF, Sacks GS, Kudsk K a. Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Heal Pharm. 2005;62:1663-1682. doi:10.2146/ajhp040300.
  3. Hollander-Rodriguez JC, Calvert JF. Hyperkalemia. Am Fam Physician. 2006;73(2):283-290.
  4. Weir MR. Are Drugs That Block the Renin-Angiotensin System Effective and Safe in Patients With Renal Insufficiency? Am J Hypertens. 1999;7061(99):195-203.
  5. Einhorn LM, Zhan M, Hsu VD, et al. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169(12):1156-62. doi:10.1001/archinternmed.2009.132.
  6. Pitt B, Collins AJ, Reaven N, Funk S, Bakris GL, Bushinsky DA. Abstract 13320: Effect of Cardiovascular Comorbidities on the Mortality Risk Associated with Serum Potassium. Circulation. 2014;130.

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