Date of publication: January 12, 2017

News & Views

The Challenge of Chronic Hyperkalemia

Controlling potassium levels in CKD patients requires a complex combination of dietary awareness, medication control and targeted therapy. This article, and the accompanying educational slide pack, outline the issues facing clinicians when managing hyperkalemia, the current treatment options and requirements for future therapies.

Hyperkalemia is defined as serum potassium levels over 5.0 mmol/L, although thresholds can vary up to 5.5 mmol/L depending on the study referenced. Hyperkalemia diagnosis is complicated by patients often being asymptomatic until levels reach >5.5 mmol/L, and also by its non-specific symptoms including palpitations, nausea, weakness and muscle pain.[1]

The most common cause of hyperkalemia is reduced excretion of potassium by the kidneys as a result of chronic kidney disease (CKD),[2] but use of renin-angiotensin-aldosterone system (RAAS) inhibition to treat hypertension is another significant factor.[3] In patients with CKD, the prevalence of hyperkalemia is correlated with disease severity (Figure 1).[2]

prevalence of hyperkalaemia

Figure 1: Percentage of CKD patients with serum potassium >5.5 mmol/L increases with disease severity


The increased risk of hyperkalemia associated with RAAS blockade is a result of the impact of RAAS inhibition on renal function,3 and is particularly evident when RAAS inhibitors are used in combination with each other.[4] A meta-analysis showed a 55% increase in relative risk of hyperkalaemia with dual RAAS blockade compared with monotherapy.[4]

Decreasing RAAS inhibitor use and avoiding dual therapy might seem like a simple solution, but RAAS inhibition has been shown to have significant renal and cardiovascular benefits beyond treating hypertension[5] and heart failure.[6] Limiting dietary potassium is also difficult to follow as potassium is found in many fruits and vegetables and also in dairy products, and as a consequence such restricted diet is often poorly adhered to.[5]

Current treatment options for hyperkalemia include the potassium binders calcium polystyrene sulfonate (CPS) and sodium polystyrene sulfonate (SPS). Although effective in reducing serum potassium, they are not adapted to chronic usage given precautions associated with their utilisation. In addition, use of sodium polystyrene sulfonate is associated with gastrointestinal toxicity.[5]

Hyperkalemia represents a serious complication for patients with CKD. Future treatment of hyperkalemia needs a therapy which can effectively, and tolerably, lower serum potassium in a range of patient populations without compromising common concomitant therapies.


  1. 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.
  2. 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.
  3. 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.
  4. Makani H, Bangalore S, Desouza K a, Shah A, Messerli FH. Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials. BMJ. 2013;346(January):f360. doi:10.1136/bmj.f360.
  5. Pitt B, Bakris GL. New potassium binders for the treatment of hyperkalemia: Current data and opportunities for the future. Hypertension. 2015;66(4):731-738. doi:10.1161/HYPERTENSIONAHA.115.04889.
  6. Pitt B, Zannad F, Remme WJ, et al. The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. N Engl J Med. 1999;341(10):709-717. doi:10.1056/NEJM199909023411001.

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