Hyperkalemia in CKD

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1. Referral for urgent management of hyperkalemia

• Current guidelines suggest that the following outpatients should be referred for urgent management
  • K+ > 6.0 mEq/L with OR without ECG changes 
  • Anyone with hyperkalemia and documented EKG changes 
• However, there is no consensus on these recommendations and many clinicians manage hyperkalemia in the outpatient setting differently (especially with hyperkalemia < 6.0 mEq/L)

2. Hyperkalemia and ECG changes

• A retrospective chart review of about 90 patients admitted with severe hyperkalemia (K+ > 6 mEq/L (most patients had K+ < 7.2 mEq/L), who also received an ECG. 
  • Only 52% had ECG changes.  
  • Study authors could not identify a threshold at which you would see an EKG change.  
• Recent retrospective study from 2019 compared ECG findings of 3 cohorts - K+ < 5.1 mEq/L (normokalemia), K+ between 6 and 7 mEq/L (moderate hyperkalemia), and K+ > 7.0 mEq/L (severe hyperkalemia)
  • No significant difference in the frequency of ECG changes were found between the normokalemia and moderate hyperkalemia group
  • More than half of all the hyperkalemic patients, including severe hyperkalemia, did NOT have any ECG changes.  

Take-home point: ECGs are not sensitive at all in the detection of hyperkalemia.  The absence OR presence of EKG changes does not predict the presence of hyperkalemia.

• Case report from Japan presents a patient with an initial K+ of 8.5 mEq/L and a normal ECG
  • Returned <1 week later with recurrent K+ to 8.6 mEq/L. 
  • ECG now shows a sine wave pattern
• No consensus or solid data on what “chronic” hyperkalemia means, with respect to how high or how long a patient needs to have it

Take-home point: The abrupt change from normokalemia to severe hyperkalemia, not necessarily the K+ level itself, is most worrisome and needs to be treated.

3. Pseudo-hyperkalemia

• Conditions that lead to pseudo-hyperkalemia, the in vitro release of intracellular K+
  • Excessive tourniquet use
  • Fist clenching
  • Vein trauma from multiple phlebotomy attempts 
  • PICC/central line draws
  • Use of serum separator tube (clot activators) - commonly used to measure the “basic metabolic panel” 
• Sending a whole blood sample, sent to the lab in an anticoagulated tube, is the most reliable way to get an accurate potassium reading

4. K+ restricted diets

• Taking a detailed dietary history helps guide management
  • Common high K+ foods (“restriction” = < 2 g per day)
    • Fruits - oranges, mangoes, avocadoes, melon, prunes, raisins, dates
    • All types of potatoes, including yuca and yams   
    • Common side dishes, sauces, and snacks - tomatoes and tomato sauce, spinach, beans, lentils
    • Salt substitutes often contain potassium chloride (KCl)
  • Pro-tips for avoid complete K+ elimination from the diet include:
    • Focus on moderation and portion size rather complete elimination
    • Leach K+ from potatoes
    • Drain liquids from cooked fruits, vegetables, and meats
• High K+ diets have been linked to better blood pressure control and improved cardiovascular mortality in patients with hypertension. 
  • K+-rich diets also have high amounts of alkali, which counteract the metabolic acidosis of CKD
    • Metabolic acidosis both worsens hyperkalemia AND contributes to the progression of CKD and higher mortality

Low K+ diet results in increased Na+ reabsorption, and worsening blood pressure control 

Take-home point: Complete elimination of K+ from the diet is not advisable.  High K+ foods should be consumed in moderation, as they provide significant cardiovascular health benefits, especially for those with CKD.

5. Key medications that can cause hyperkalemia

• RAASi improve mortality, but are often the first medications to be discontinued when hyperkalemia is detected

• Difficult to predict how much the K+ will improve with stopping a RAASi
  • Opposing driving forces for each individual’s potassium balance
    • Diabetes and lower baseline estimated GFR have higher propensity for high K+
      • Lack of insulin OR increased insulin resistance lead to a less robust insulin surge with meals (and less intracellular potassium shift)
      • Common etiology of hyporeninemic hypoaldosteronism  

NSAIDS and antibiotics are common medication offenders in hyperkalemia

• NSAIDs (and beta blockers) decrease renin release (and less RAAS activation), with decreased K+ excretion
• Antibiotics - the TMP component of TMP-SMX blocks potassium excretion in the collecting duct of the nephron

6. Treating outpatient hyperkalemia

• Sodium polystyrene sulfonate (SPS, a.k.a Kayexalate)
  • Most of the data on SPS is retrospective, without any RCTs
  • Retrospective cohort study of 1.8 million patients over age 66 
  • SPS users had 2x higher rates of GI events vs. controls
    • GI events = intestinal ischemia, thrombosis, ulceration, perforation, resection, or ostomy creation
  • Adverse effects more common with pre-existing or active GI conditions
  • Most patients find SPS difficult to drink, as it tastes disgusting

• Patiromer 
  • Gemstone trials - AMETHYST, OPAL-HK, and AMBER
    • Patiromer is effective at lowering K to more manageable levels 
    • High proportions of patients were able to stay on their RAASi 
    • Main side effects were hypomagnesemia and constipation, both reversible and manageable

• Sodium zirconium cyclosilicate, SZC
  • Influential trials include HARMONIZE and ENERGIZE. 
  • The NEJM study in 2015 showed that 1 dose of SZC has a rapid onset, with normokalemia achieved in an average time of 2.2 hours 
  • Main side effect = occasional edema (from the sodium load), without any increase in blood pressure
  • Patient tolerability is much better - easy to take and tasteless

Those named above unless otherwise indicated have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

*Dr. Joshi reports receiving honoraria from NKF and Vita Pharma, and is a Consultant for Insyght Interactive.

These relationships have been mitigated.

Release Date:  November 17, 2021

Expiration Date: November 17, 2024

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