• Information
  1. Causes
  2. Drug Induced Hyperkalemia
  3. Familial Syndromes
  4. Symptoms and Signs
  5. Treatment of Acute or Symptomatic Hyperkalemia
  6. Considerations in Reducing Hyperkalemia Risk

A. Causes

1. Drugs (see below) [1,2]
2. Foods - particularly salt substitutes that use potassium (K+) chloride [3]
3. Renal Failure - acute or chronic
4. Acidosis
   1. Acid pH shifts cause K+ to exit cells
   2. Basic pH shifts cause K+ to enter cells
   3. Diabetic ketoacidosis [7]
5. Tumor Lysis Syndrome
6. Renal Tubular Acidosis Type IV (see below)
7. Adrenal Insufficiency
8. Hypoaldosteronism
9. Pseudohyperkalemia - secondary to very high cell counts (thrombocytosis, neutrophilia)
10. Contributing Factors
    1. Volume depletion
    2. Heart failure
    3. Chronic kidney disease
    4. Advanced age
    5. Diabetes mellitus

B. Drug Induced Hyperkalemia [1,2]

1. Potassium (K+) salts
   1. Potassium supplements; salt substitutes
   2. Stored pack red blood cells
   3. Penicillin G potassium
   4. Nutritional and herbal supplements
2. Drugs which Impair Renal Excretion
   1. Potassium sparing diuretics (see below)
   2. Angiotensin converting enzyme (ACE) inhibitors
   3. Angiotensin II receptor blockers (ARB)
   4. Nonsteroidal antiinflammatory drugs (NSAIDS)
   5. Trimethoprim
   6. Pentamidine
   7. Calcineurin Inhibitors: Cyclosporin and tacrolimus
   8. Heparin
   9. Ketoconazole - impairs aldosterone metabolism, reduces aldosterone
   10. ß-adrenergic receptor blockers - reduce renin secretion, reduce cellular K+ uptake
3. Transcellular K+ Shifts
   1. beta-adrenergic blockers
   2. Digoxin intoxication
   3. Succinylcholine
   4. Intravenous amino acids
4. ACE inhibitors (ACE-I) and ARB [1,4,5]
   1. ACE-I reduce GFR as well as aldosterone levels
   2. ARB primilary affect GFR
   3. ACE-I or ARB induced hyperkalemia is rarely severe when used alone
   4. Injestion of foods containing large K+ loads can precipitate hyperkalemia with ACE-I/ARB
   5. These include fruit juices, bananas [6]
   6. Increasing use of spironolactone or eplerenone with ACE-I or ARB increase hyperkalemia [4]
5. K+ Sparing Diuretics [4]
   1. Particularly in combination with ACE-I or ARB
   2. Aldosterone antagonists: Spironolactone (Aldactone®) or eplerenone
   3. Amiloride
   4. Triampterene
6. High dose Trimethoprim-Sulfamethoxazole (TMP/SMX)
   1. Blocks apical membrane Na+ channels in distal nephron (like amiloride)
   2. This reduces transepithelial voltage, inhibiting K+ secretion
   3. Common in HIV+ / AIDS on chronic TMP/SMX (Bactrim®)
   4. Standard dose TMP/SMX intravenously may lead rarely to hyperkalemia

C. Familial Syndromes

1. Pseudohypoaldosteronism Type 1 [8]
   1. End organ resistance to aldosterone
   2. Present in first week of life with dehydration, hyponatremia, hyperkalemia
   3. Type 1 disease associated with mineralocorticoid resistance
   4. Type 1 has autosomal dominant and recessive forms
   5. Type 1 recessive is due to defects in alpha, beta, and/or gamma subunits of Na+ channel
   6. Type 1 dominant is due to mutations in the mineralocorticoid type I receptor
   7. Four distinct mutations have been described in each of the recessive and dominant forms
   8. Airway epithelial Na+ transport abnormal, with increased fluid in lungs found [9]
2. Pseudohypoaldosteronism Type 2 [10]
   1. Also called familial hyperkalemic hypertension or Gordon syndrome
   2. Rare, autosomal dominant form of hyperkalemia
   3. Deletions in WNK1 or missense mutations in WNK4 genes demonstrated
   4. Impaired renal potassium excretion
   5. Hyperchloremic metabolic acidosis
   6. Hypertension
   7. Normal glomerular filtration rate
   8. Respond to thiazide diuretics

D. Symptoms and Signs

1. Symptoms depend on rate of change of [K+]; rapid changes are more symptomatic
2. Hyperkalemia is most severe life threatening electrolyte disorder
   1. Can cause Ventricular fibrillation
   2. Precipitate Myocardial Infarction
3. Peaked T waves on ECG (very rapid test to screen for suspected hyperkalemia)
4. Muscle Fatigue
5. Tachypnea (to correct metabolic alkalosis)
6. Polyuria - increased K+ and H+ secretion and secondary increase in aldosterone

E. Treatment of Acute or Symptomatic Hyperkalemia

1. Stabilize Cardiac Muscle
   1. Calcium Gluconate IV 2 amps
   2. Given for any sign of cardiac impairment or instability
   3. Very safe and effective
2. Increase K+ Uptake By Cells
   1. Insulin 10U regular IV + 1 amp of 50% Dextrose Solution
   2. Alkalinize Plasma with NaHCO3 - several amps in D5W
3. Intravenous loop diuretic (such as furosemide 40-60mg iv)
   1. Method for fairly rapid reduction in total body potassium levels
   2. Especially useful in volume overloaded patients
   3. Concern for magnesium and other electrolyte depletion
4. Decrease Body Potassium
   1. Oral Sodium Polystyrene Sulfonate (Kayexelate®) 15-30gm
   2. Usually given in sorbitol solution to promote diarrhea (with further K+ loss)
   3. Requires >8-12 hours to work

F. Considerations in Reducing Hyperkalemia Risk [1]

1. Increasing number of drugs associated with hyperkalemia
2. Estimate Renal Function to assess specific Hyperkalemia Risk
   1. Glomerular filtration rate (mL/min/1.73m2) = 186 x serum creatinine (mg/dL) x age (yr)
   2. For women, multiply GFR above by 0.742; for blacks, multiply by 1.210
   3. Creatinine clearance (mL/min) = (140-age)xweight (kg) / (creatinine x 72)
   4. For women, multiply CrCl above by 0.85
   5. Persons with reduced GFR or CrCl (especially <30mL/min) have increased hyperkalemia risk
3. If possible, discontinue drugs which interfere with potassium excretion
   1. Reduce or eliminate use of NSAIDs and COX-2 selective inhibitors
   2. Inquire about use of herbal preparations
4. Low potassium diet and elimination of potassium containing salt substitutes
5. Thiazide or loop diuretics reduce serum K+ levels, increase renal K+ loss
6. In patients with renal dysfunction and acidosis, sodium bicarbonate to reduce acidosis
7. Initiation of low dose ACE-I or ARB with at least weekly monitoring K+, creatinine
8. Increase in K+ with Drugs
   1. If K+ levels increase >5.4mmol/L, reduce dose of ACE-I or ARB and/or other drugs
   2. If K+ levels do not drop <5.5mmol/L with appropriate measures, discontinue ACE-I or ARB
9. Addition of Aldosterone Blocker
   1. Do not use combination ACE-I/ARB with aldosterone blocker if GFR<30mL/min
   2. Dose of spironolactone should not exceed 25mg qd in combination with ACE-I or ARB

References

1. Palmer BF. 2004. NEJM. 351(6):585
2. Perazella MA. 2000. Am J Med. 109(4):307
3. Hoye A and Clark A. 2003. Lancet. 361(9375):2124
4. Juurlink DN, Mamdani MM, Lee DS, et al. 2004. NEJM. 351(6):543
5. Reardon LC and Macpherson DS. 1998. Arch Intern Med. 158(1):26
6. Williams E and Fulop M. 2001. Lancet. 357(9263):1176 (Case Report)
7. Tran HA. 2006. Am J Med. 119(6):487 (Case Discussion)
8. Scheinman SJ, Guay-Woodford L, Thakker RV, Warnock DG. 1999. NEJM. 340(15):1177
9. Kerem E, Bistritzer T, Hanukoglu A, et al. 1999. NEJM. 341(3):156
10. Achard JM, Warnock DG, Disse-Nicodeme S, et al. 2003. Am J Med. 114(6):495