Evaluation of hyperkalemia

Relates to decreased ability to excrete potassium. Can occur early in the course of chronic kidney disease, particularly in patients with diabetes or hyporeninemic hypoaldosteronism. Less common than in the case of acute kidney failure, in that adaptive gastrointestinal and cellular processes evolve to facilitate potassium handling. Urine flow rate and sodium intake are important determinants of potassium clearance by the chronic renal failure kidney.

In lupus erythematosus, decreased tubular secretion of potassium relating to tubulointerstitial disease is sometimes disproportionate to the level of renal function.

Increase in serum creatinine values more closely approximate glomerular filtration rate than in the case of acute kidney failure. Potassium excretion begins to decrease at a glomerular filtration rate of about 30 mL/minute. Often appears in the setting of potassium supplements being given and/or potassium-sparing medications being administered.

Relates to the extracellular movement of fluid and potassium (solvent drag) in response to the higher extracellular osmolality attributable to hyperglycemia. The effect on serum potassium values of the hyperglycemia-related extracellular shift in potassium can be quite variable, relating in part to the extent to which total body potassium stores have been depleted.

Digoxin overdose: dysrhythmias associated with increased automaticity such as accelerated junctional rhythms or bidirectional ventricular tachycardia, premature ventricular contractions, bigeminy, trigeminy, complete atrioventricular dissociation, third-degree heart block, ventricular fibrillation, asystole.

Arginine hydrochloride: life-threatening arrhythmias can occur rapidly with arginine in patients with hepatic disease who more poorly metabolize arginine and in patients with pre-existing renal failure and/or diabetes mellitus.

Beta-blockers: life-threatening arrhythmias are uncommon with beta-blockers since the associated increase in serum potassium values is both minor and transient.

Alternative drug options may be necessary before discontinuation of offending drug.

Timing of sampling important to determination of chronic toxicity. Blood samples obtained within 6 to 8 hours of ingestion may be falsely elevated since the drug has yet to completely distribute to body tissues.

The risk of hyperkalemia is proportional to the level of renal function, but the serum potassium can increase significantly with only moderate renal failure in the setting of hyporeninemic hypoaldosteronism.

Poor correlation between the degree of change in clotting parameters and increases in serum potassium values.

Can occur at normal therapeutic plasma levels. More common with high plasma levels of the calcineurin inhibitor.

Can occur at normal therapeutic plasma levels. More common with high plasma levels of the calcineurin inhibitor.

Relates to decreased ability to excrete potassium. Can occur early in the course of acute kidney failure, often relating to hypercatabolic state and/or having received potassium supplements. Less common in nonoliguric forms of disease.

Confirm the diagnosis of AKI if there is:[39]Kidney Disease: Improving Global Outcomes (KDIGO). Acute kidney injury (AKI)​. Mar 2012 [internet publication]. https://kdigo.org/guidelines/acute-kidney-injury

a rise in serum creatinine of ≥0.3 mg/dL (≥26 micromol/L) within 48 hours

OR

a rise in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the past 7 days

Increase in serum creatinine values can lag behind rises in serum potassium. Serum creatinine values poorly reflect level of renal function and can be minimally elevated in the presence of significant changes in potassium homeostasis.

Relates to decreased ability to excrete potassium. Metabolic acidosis and hyperkalemia are disproportionate to the level of renal failure, especially in patients with hyporeninemic hypoaldosteronism. Often appears in the setting of potassium supplements being given and/or potassium-sparing medications being administered.

Nonanion gap form of metabolic acidosis.

In patients with a pH <5.5 normal plasma cortisol with a low aldosterone value establishes diagnosis of selective aldosterone deficiency. If plasma cortisol and aldosterone are low, Addison disease is likely present. A voltage-dependent form of renal tubular acidosis is present when urine pH is >5.5 and hyperkalemia is present.

Relates to movement of potassium from the intracellular to the extracellular location as hydrogen ions move intracellularly. Minimal transcellular shifts of potassium occur with respiratory acidosis. The degree of change in serum potassium concentration is difficult to predict for any specific fall in pH.

This can be reflected in either an anion gap or a nonanion gap metabolic acidosis. The effect on serum potassium with an acidosis is more so with the inorganic than with organic acidosis such as lactic acidosis and ketoacidosis.

Necessary for the diagnosis of metabolic acidosis, since a low bicarbonate value can also be seen as a compensatory response to respiratory alkalosis.

This test is particularly useful for newborns (after the first day of life) and for infants with ambiguous genitalia or at risk for 21-hydroxylase deficiency. Hemolyzed blood gives rise to a false-positive result.

Ideally, medications should be stopped at least 3 weeks prior to sample collection.

High plasma renin activity levels indicate low serum sodium.

A cortisol precursor that accumulates in elevated concentrations in 21-hydroxylase deficiency.

Both parents should have genetic testing to determine if they carry the mutation. If both parents are carriers, prenatal treatment is recommended until genetic diagnosis of the fetus can be performed via amniocentesis or chorionic villus sampling.

Relates to inability to excrete potassium effectively. Hyperkalemia becomes most prominent when mechanisms for intracellular migration of potassium are defective.

Urine potassium is typically low, reflecting an absence of aldosterone effect. Spot urine samples are difficult to interpret. 24-hour samples are typically less than dietary potassium intake.

Any stressful condition will increase cortisol levels. A value of 25 microgram/dL will exclude Addison disease.

When potassium values are repetitively checked during attack-free intervals, high or normal values can often be detected.

Supportive diagnostic criteria for hyperkalemic periodic paralysis include: ≥2 attacks of muscle weakness with serum potassium >4.5 mEq/L (>4.5 mmol/L); or 1 attack of muscle weakness in the proband, and 1 attack of weakness in a relative with serum potassium >4.5 mEq/L (>4.5 mmol/L) in ≥1 attack.[40]Statland JM, Fontaine B, Hanna MG, et al. Review of the diagnosis and treatment of periodic paralysis. Muscle Nerve. 2018 Apr;57(4):522-30. https://onlinelibrary.wiley.com/doi/10.1002/mus.26009 http://www.ncbi.nlm.nih.gov/pubmed/29125635?tool=bestpractice.com

Level of hyperkalemia relates to tumor burden, level of proliferation, and rapidity of tumor turnover with chemotherapy, in addition to level of renal function. Usually occurs within 1 to 3 days of initiating chemotherapy.

Biochemistry should be performed prior to initiation of cancer treatment, and for 2 to 3 days after initiation of treatment.

Elevated uric acid prior to initiation of cancer treatment correlates with large tumor burden and is considered an independent risk factor for tumor lysis syndrome.

Significantly increased release of phosphate, particularly in tumors such as Burkitt lymphoma. Increase in calcium/phosphate product with tissue deposition of same and development of hypocalcemia.

Hypocalcemia is a defining feature of imaging tumor lysis syndrome.

Elevated creatinine prior to initiation of cancer treatment is an independent risk factor for tumor lysis syndrome.

Preexisting renal impairment (elevated serum creatinine ≥1.5 times the upper limit of normal), dehydration (with elevated urea), and volume depletion are predisposing risk factors for tumor lysis syndrome that may be modifiable and should be identified prior to initiation of cancer treatment.

Level of hyperkalemia relates to extent of muscle damage and presence of acute kidney failure.

In exercise-related hyperkalemia without rhabdomyolysis, hyperkalemia may be attributable to a Na+-K+ pump that does not keep pace with K+ efflux from muscle during the depolarization-repolarization process of the sarcolemmal membrane during muscle contraction.[41]Wasserman K, Stringer WW, Casaburi R, et al. Mechanism of the exercise hyperkalemia: an alternate hypothesis. J Appl Physiol 1997;83:631-643. http://jap.physiology.org/cgi/content/full/83/2/631 http://www.ncbi.nlm.nih.gov/pubmed/9262462?tool=bestpractice.com [42]Clausen T. Quantification of Na+,K+ pumps and their transport rate in skeletal muscle: functional significance. J Gen Physiol. 2013 Oct;142(4):327-45. https://rupress.org/jgp/article/142/4/327/43333/Quantification-of-Na-K-pumps-and-their-transport http://www.ncbi.nlm.nih.gov/pubmed/24081980?tool=bestpractice.com

Analytical assessment of serum creatinine may have falsely increased values owing to release of noncreatinine chromogens from damaged muscle.

Myoglobin released from muscle enters the urine freely and registers a false positive for blood.

Test-tube phenomenon due to release of potassium into serum from cells undergoing lysis during the clotting process, a time-dependent process relating to delayed processing.

Potassium value in serum is artifactually elevated secondary to red blood cell hemolysis. Bloody tinge to appearance of the serum. Avoid repeated blood draw with syringe and heavy suctioning.

Relates to loss of sodium chloride into jejunal fluid and absorption of potassium.

The degree to which secondary hyperaldosteronism occurs owing to loss of sodium chloride determines urinary potassium levels and the degree to which hyperkalemia develops.