eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders

Hypokalemia: Differential Diagnoses & Workup

Author: Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Coauthor(s): Rosemary Ouseph, MD, Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine; Leslie Ford, MD, Assistant Professor of Medicine, Kidney Disease Program, University of Louisville School of Medicine
Contributor Information and Disclosures

Updated: Aug 5, 2009

Workup

Laboratory Studies

  • Urine potassium: This test is of vital importance because it establishes the pathophysiologic mechanism and, thus, helps formulate the differential diagnosis.
    • A spot urine potassium measurement is, for obvious reasons, the easiest and most commonly obtained test. Low urine potassium (<20 mEq/L) suggests poor intake, a shift into the intracellular space, or gastrointestinal loss. High urine potassium (>40 mEq/L) suggests renal loss.
    • A spot urine sodium and osmolality test obtained simultaneously with a spot urine potassium test can help refine the interpretation of the urine potassium level. A low urine sodium level (<20 mEq/L) with a high urine potassium level suggests the presence of secondary hyperaldosteronism. If the urine osmolality is high (>700 mOsm/kg), then the absolute value of the urine potassium concentration can be misleading and can suggest that the kidneys are wasting potassium.
      • For example, suppose the serum potassium level is 3 mEq/L and the urine potassium level is 60 mEq/L. The high urine potassium level would suggest renal potassium loss. However, the final concentration of potassium in the urine is dependent not only on the quantity of potassium secreted in response to sodium reabsorption, but also on the concentration of the urine.
      • In the above example, if urine osmolality is 300 mOsm/kg, ie, not concentrated relative to serum, then a measured urine potassium of 60 mEq/L indeed suggests renal potassium loss. However, if the urine osmolality is 1200 mOsm/kg, ie, concentrated 4-fold relative to serum, then the potassium concentration in the urine, in the absence of urinary concentration due to water reabsorption, is 15 mEq/L, ie, very low.
      • The conclusion would then be that the kidneys are not responsible for the low serum potassium.
    • To account for the potentially confounding effect of urine concentration on the interpretation of the urine potassium concentration, a calculation called the transtubular potassium gradient (TTKG) has been developed.17,18 This test, in effect, back-calculates what the serum-to-tubular fluid ratio of potassium would be at the level of the cortical collecting tubule, where potassium is secreted before urine concentration has occurred. 
      • Performing this test requires measuring serum and urine potassium levels and osmolality according to the following equation:
      • TTKG = (Urine potassium X serum osm )/(serum potassium X urine osm)
      • A value less than 3 suggests that the kidney is not wasting excessive potassium, while a value greater than 7 suggests a significant renal loss. This test cannot be applied when the urine osmolality is less than the serum osmolality.
  • Urine potassium in 24 h: While more cumbersome to obtain, a 24-hour urine measurement of potassium excretion yields more precise data on exactly how much potassium is being lost through renal excretion.
    • Because the kidneys are able to conserve potassium up to approximately 10-15 mEq/d, a value of less than 20 mEq/24-hour urine specimen suggests appropriate renal conservation of potassium, while values above that indicate some degree of renal wasting.
    • To ensure that a full and accurate 24-hour urine sample has been collected, urine creatinine should be measured simultaneously.
  • Basic metabolic profile: Measure electrolytes, BUN, and creatinine.
  • Serum sodium level
    • Low serum sodium suggests thiazide diuretic use or marked volume depletion from gastrointestinal losses.
    • High serum sodium might suggest that nephrogenic diabetes insipidus has occurred secondary to hypokalemia. This could indicate that the hypokalemia is a long-standing problem. A high serum sodium level also might suggest the presence of primary hyperaldosteronism, especially if hypertension also is present.
  • Serum bicarbonate level
    • A low serum bicarbonate level might suggest renal tubular acidosis, diarrhea, or the use of carbonic anhydrase inhibitors.
    • A high serum bicarbonate level is consistent with either primary hyperaldosteronism or secondary hyperaldosteronism. Causes of secondary hyperaldosteronism could be exogenous prednisone therapy, vomiting, or the use of thiazide or loop diuretics. A high serum bicarbonate level is also consistent with Bartter, Gitelman, or Liddle syndrome.
  • Hyperglycemia might suggest that the hypokalemia has been of sufficient severity and duration to impair glucose tolerance.
  • Creatine kinase: Occasionally, hypokalemia will be of sufficient severity to produce not only muscle weakness but also frank rhabdomyolysis. This most often occurs in the setting of alcoholism, where total body potassium stores may be quite low due to prolonged periods of poor intake. Severe rhabdomyolysis can lead to renal failure and subsequent severe hyperkalemia.
  • Magnesium: Often, severe hypokalemia is associated with significant magnesium losses and cannot be corrected unless the hypomagnesemia is corrected.
  • Algorithm for evaluation of hypokalemia: Complete history and physical examination can reveal the cause in most cases, negating the need for extensive testing.
    • Urine potassium level less than 20 mEq/L suggests gastrointestinal loss, poor intake, or shift of potassium into cells. Question the patient regarding (1) diarrhea and use of laxatives; (2) diet and TPN contents; and (3) the use of insulin, excessive bicarbonate supplements, and episodic weakness.
    • A urine potassium level higher than 40 mEq/L suggests renal loss.
      • Examine the patient's medication list. Question the patient regarding the use of diuretics.
      • Look at the acid-base balance; alkalosis suggests vomiting, Bartter syndrome, Gitelman syndrome, diuretic abuse, or mineralocorticoid excess. Acidosis suggests renal tubular acidosis types I or II or Fanconi syndrome (as is observed with paraproteinemias, amphotericin use, gentamicin use, or glue sniffing [toluene abuse]).
      • Measure the magnesium level; if low, correct it before attempting to correct the potassium level.
      • Measure the patient's blood pressure. Elevated blood pressure suggests primary hyperaldosteronism, Cushing syndrome, congenital adrenal hyperplasia, glucocorticoid-remediable hypertension, renal artery stenosis, or Liddle syndrome. Low blood pressure suggests diuretic abuse or a renal tubular disorder such as Bartter syndrome, Gitelman syndrome, or renal tubular acidosis.
    • If the urine potassium level is higher than 20 mEq/L but lower than 40 mEq/L, calculate the TTKG.
      • A TTKG of less than 3 suggests that renal loss is not a cause of hypokalemia.
      • A TTKG greater than 7 suggests mineralocorticoid excess.
      • A middle value may indicate a mixed disorder.

Imaging Studies

  • Imaging techniques are not used as first-line studies. See Other Tests.

Other Tests

  • Perform an ECG to determine whether the hypokalemia is affecting cardiac function or to detect digoxin toxicity. ECG may show atrial or ventricular tachyarrhythmias, decreased amplitude of the P wave, or appearance of a U wave.
  • In most cases, the cause of hypokalemia is apparent from the history and physical examination and is confirmed by the measurement of urine potassium. By far the most common causes are losses due to diuretics or gastrointestinal disorders. Depending on history, physical examination findings, clinical impressions, and urine potassium results, the following tests may be appropriate, but they should not be first-line tests unless the clinical index of suspicion for the disorder is high.
    • Diuretic screen in urine and/or serum
    • Serum renin, aldosterone, and cortisol
    • 24-hour urine aldosterone, cortisol, sodium, and potassium
    • Pituitary imaging to evaluate for Cushing syndrome
    • Adrenal imaging to evaluate for adenoma
    • Renal angiogram to evaluate for renal artery stenosis
    • Enzyme assays for 17-beta hydroxylase deficiency

More on Hypokalemia

Overview: Hypokalemia
Differential Diagnoses & Workup: Hypokalemia
Treatment & Medication: Hypokalemia
Follow-up: Hypokalemia
References
Further Reading
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Further Reading

Related eMedicine topics:
Bartter Syndrome [Nephrology]
Bartter Syndrome [Pediatrics: General Medicine]
Conn Syndrome
Hyperaldosteronism [Pediatrics: General Medicine]
Hyperaldosteronism [Radiology]
Hyperaldosteronism, Primary
Hyperkalemia [Emergency Medicine]
Hyperkalemia [Nephrology]
Hyperkalemia [Pediatrics: Cardiac Disease and Critical Care Medicine]
Hypokalemia [Emergency Medicine]
Hypokalemia [Pediatrics: Cardiac Disease and Critical Care Medicine]
VIPoma
VIPomas

Clinical guidelines:
Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine Society clinical practice guideline. The Endocrine Society - Disease Specific Society.  2008 Sep.  26 pages.  NGC:006766

Hyperglycemic crises in diabetes. American Diabetes Association - Professional Association.  2000 Oct (revised 2001; republished 2004 Jan).  9 pages.  NGC:003428

Clinical trials:
Safety of Continuous Potassium Chloride Infusion in Critical Care (ASPIC)

Spironolactone to Decrease Potassium Wasting in Hypercalciurics on Thiazides Diuretics

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Keywords

hypokalemia, low potassium, symptoms of low potassium, lack of potassium, causes of low potassium, low potassium symptoms, Bartter's syndrome, Gitelman's syndrome, Bartter syndrome, Gitelman syndrome, symptoms of hypokalemia, potassium homeostasis, potassium excretion, potassium intake

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Contributor Information and Disclosures

Author

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Rosemary Ouseph, MD, Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine
Rosemary Ouseph, MD is a member of the following medical societies: American Society for Bone and Mineral Research, American Society of Nephrology, and American Society of Transplant Surgeons
Disclosure: Nothing to disclose.

Leslie Ford, MD, Assistant Professor of Medicine, Kidney Disease Program, University of Louisville School of Medicine
Leslie Ford, MD is a member of the following medical societies: American Medical Association, American Society of Nephrology, and Kentucky Medical Association
Disclosure: Nothing to disclose.

Medical Editor

James W Lohr, MD, Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo
James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Christie P Thomas, MBBS, FRCP, FASN, FAHA, Professor, Department of Internal Medicine, Division of Nephrology; Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics
Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Nephrology, American Society of Transplantation, American Thoracic Society, International Society of Nephrology, and Royal College of Physicians
Disclosure: Genzyme Grant/research funds Other

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
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