Hypernatremia Workup

Updated: Jan 03, 2023
  • Author: Ivo Lukitsch, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Laboratory Studies

The diagnosis of hypernatremia is based on an elevated serum sodium concentration (Na+ >145 mEq/L). In addition, the following lab studies are used to determine the etiology of hypernatremia:

  • Serum electrolytes (Na +, K +, Ca 2 +)
  • Glucose level
  • Urea
  • Creatinine
  • Urine electrolytes (Na +, K +)
  • Urine and plasma osmolality
  • 24-hour urine volume
  • Plasma arginine vasopressin (AVP) level (if indicated)

The first step in the diagnostic approach is to estimate the volume status (intravascular volume) of the hypernatremic patient. The associated volume contraction may be mirrored in a low urine Na+ (usually < 10 mEq/L).

In the hypovolemic patient, a hypertonic urine (urine osmolality usually greater than 600 mOsm/kg) with a low UNa+ (usually less than 10–20 mEq/L) will point toward extrarenal fluid losses (eg, gastrointestinal, dermal), whereas an isotonic or hypotonic urine (urine osmolality 300 mOsm/kg or less) with a UNa+ higher than 20–30 mEq/L indicates renal fluid loss (eg, from diuretics, osmotic diuresis, intrinsic renal disease).

In the euvolemic patient with preserved intravascular volume, hypernatremia is most likely due to pure-water losses. In the presence of hypernatremia, urine osmolality normally should be maximally concentrated (>800 mOsm/kg H2O). Measurement of the urine osmolality will allow differentiation of the following:

  • Nonrenal causes with appropriately high urine osmolality - Isolated hypodipsia, increased insensible losses
  • Renal water loss indicated by inappropriately low urine osmolality - Diabetes insipidus (often U osm< 300 mOsm/kg H 2O [central, nephrogenic, partial, gestational diabetes insipidus])

Caveat: Unfortunately, concentrating ability tends to fall with age; the maximum Uosm in an elderly patient may be only 500-700 mOsm/kg.

To distinguish between central and nephrogenic diabetes insipidus, first obtain a plasma AVP level and then determine the response of the urine osmolality to a dose of AVP (or preferably, the V2-receptor agonist DDAVP). Generally, an increase in urine osmolality of greater than 50% reliably indicates central diabetes insipidus, while an increase of less than 10% indicates nephrogenic diabetes insipidus; responses between 10% and 50% are indeterminate. Hyperosmolar patients with an elevated AVP level have nephrogenic diabetes insipidus; those with central diabetes insipidus will have inadequately low AVP level.

If the patient has polyuria without hypernatremia and will be evaluated for diabetes insipidus, the plasma sodium has to be above 145 mOsm/kg H2O prior to testing (via water deprivation test, hypertonic saline).

Calculating the free-water clearance (cH2O), which measures the amount of solute-free water excreted by the kidney, is usesful. However, this includes all osmoles, including urea, which does not contribute to the plasma tonicity because it freely equilibrates across cell membranes. To more accurately assess the effect of the urine output on osmoregulation, calculate the electrolyte–free-water clearance (cH2Oe), to estimate the ongoing renal losses of hypotonic fluid (cH2O = Vurine [1-(UOsm/SOsm)]; cH2Oe = Vurine [1-(UNa +UK)/SNa])

An example of the use of he above calculations is as follows: An 80-year-old, partially demented man with poor nutritional status is admitted to the hospital because of pneumonia. Hyperalimentation with high protein supplementation is started (containing 30 mEq/L each of Na+ and K+). Laboratory results over the ensuing 5 days are as follows:

  • Urine output: 4 L/day
  • BUN: 20-88 mg/dL
  • Cr: Stable at 1.4 mg/dL
  • [Na +]: From 140 mEq/L up to 156 mEq/L (despite a relatively high fluid intake)
  • Posm: 342 mOsm/kg
  • Uosm: 510 mOsm/kg
  • UNa +: 10 mEq/L
  • UK +: 42 mEq/L

The free-water clearance is calculated as follows:

cH2O = 4 x ( 1 - [510 ÷ 342] ) = –2 L/day

By this calculation, taking all osmoles into account, the patient retains 2 liters of water, improving hypernatremia; however, he is actually getting worse.

The electrolyte free-water clearance is calculated as follows:

eCH2O = 4 (1 - [(10 + 41) ÷ 156] ) = 2.7 L/day

The etiology of the hypernatremia is now apparent; the patient is losing approximately 2.7 L of free water per day in his urine, likely secondary to osmotic urea diuresis caused by hyperalimentation.


Imaging Studies

A magnetic resonance imaging (MRI) or computed tomography (CT) scan of the brain may be helpful in cases of central diabetes insipidus eventuating from head trauma or infiltrative lesions.


Histologic Findings

Histologic findings usually are noncontributory (although they may be helpful in central diabetes insipidus).