Chapter 2

Interpretation of Urine Electrolytes

and Osmolality

Measurement of urine Na+, Cl, and K+ is rather common in hospitalized patients,

and these urine electrolytes are useful in the diagnostic evaluation of volume status,
hyponatremia, acute kidney injury (AKI), metabolic alkalosis, hypokalemia and
urine anion gap (urine net charge). A spot urine sample is generally adequate for
determination of these electrolytes. In addition, urine creatinine is determined to
calculate the fractional excretion of Na+, K+, or other electrolytes. Also, urine os-
molality is helpful in the differential diagnosis of hyponatremia, polyuria, and AKI.
Table 2.1 summarizes the clinical applications of urine electrolytes and osmolality.

Certain Pertinent Calculations

Fractional Excretion of Na+ (FENa) and Urea Nitrogen

(FEUrea)

Urine Na+ excretion is influenced by a number of hormonal and other factors.

Changes in water excretion by the kidney can result in changes in urine Na+ con-
centration [Na+]. For example, patients with diabetes insipidus can excrete 10 L of
urine per day. Their urine [Na+] may be inappropriately low due to dilution, sug-
gesting the presence of volume depletion. Conversely, increased water reabsorption
by the kidney can raise the urine [Na+] and mask the presence of hypovolemia. To
correct for water reabsorption, the renal handling of Na+ can be evaluated directly
by calculating the FENa, which is defined as the ratio of urine to plasma Na+ divided
by the ratio of urine (UCr) to plasma creatinine (PCr), multiplied by 100.

Quantity of Na + excreted
FE Na ( % ) =
Quantity of Na + filtered
U + PCr
= Na 100.
PNa + U Cr

A. S. Reddi, Fluid, Electrolyte and Acid-Base Disorders, 13

DOI 10.1007/978-1-4614-9083-8_2, Springer Science+Business Media New York 2014
14 2 Interpretation of Urine Electrolytes and Osmolality

Table 2.1 Clinical applications of urine electrolytes and osmolality

Electrolyte Use
Na+ To assess volume status
Differential diagnosis of hyponatremia
Differential diagnosis of AKI
To assess salt intake in patients with hypertension
To evaluate calcium and uric acid excretion in stone-formers
To calculate electrolyte-free-water clearance
Cl Differential diagnosis of metabolic alkalosis
K+ Differential diagnosis of hypokalemia
To calculate electrolyte-free-water reabsorption
To calculate transtubular K+ gradient
Creatinine To calculate fractional excretion of Na+ and renal failure
index
To assess the adequacy of 24-h urine collection
Urine osmolality Differential diagnosis of hyponatremia
Differential diagnosis of polyuria
Differential diagnosis of AKI
Urine anion gap To distinguish primarily hyperchloremic metabolic acidosis
between distal renal tubular acidosis and diarrhea
Electrolyte-free-water clearance To assess the amount of water excretion (without solutes)
only in the management of hypo- and hypernatremia
AKI acute kidney injury

The FENais the excreted fraction of filtered Na+. The major use of FENa is in pa-
tients with AKI. Patients with prerenal azotemia have low (<1%) FENa compared
to patients with acute tubular necrosis (ATN), whose FENa is generally high (>2%).
When ATN is superimposed on decreased effective arterial blood volume due to
hepatic cirrhosis or congestive heart failure, the FENa is <2% because of the intense
stimulus to Na+ reabsorption. Similarly, patients with ATN, due to radiocontrast
agents or rhabdomyolysis have low FENa for unknown reasons.
It was shown that FENa in children with nephrotic syndrome is helpful in the
treatment of edema with diuretics. In these patients, FENa <0.2% is indicative of
volume contraction, and >0.2% is suggestive of volume expansion. Therefore, pa-
tients with FENa >0.2% can be treated with diuretics to improve edema.
The FENa is substantially altered in patients on diuretics. In these patients, the
FENa is usually high despite hypoperfusion of the kidneys. In such patients, the
FEUrea may be helpful. In euvolemic subjects, the FEUrea ranges between 50 and
65%. In a hypovolemic individual, the FEUrea is <35%. Thus, a low FEUrea seems
to identify those individuals with renal hypoperfusion despite the use of a diuretic.

Fractional Excretion of Uric Acid (FEUA) and Phosphate (FEPO4)

Uric acid excretion is increased in patients with hyponatremia due to syndrome of

inappropriate antidiuretic hormone (SIADH) secretion or syndrome of inappropri-
ate antidiuresis and cerebral salt wasting. As a result, serum uric acid level in both
Certain Pertinent Calculations 15

conditions is low (< 4 mg/dL). Since serum uric acid levels are altered by volume
changes, it is better to use FEUA. In both SIADH and cerebral salt wasting, FEUA is
> 10 % (normal 510 %). In order to distinguish these conditions, FEPO4 is used. In
SIADH, the FEPO4 is < 20 % (normal < 20 %), and it is > 20 % in cerebral salt wasting.

Transtubular K+ Gradient

Transtubular K+ gradient (TTKG) is an indirect measure of K+ secretion in the dis-

tal nephron (cortical collecting duct and to some extent late distal convoluted tu-
bule). In a healthy individual, determination of urine [K+] reflects the amount of
dietary K+ because of its secretion in the distal nephron. TTKG reflects the activity
of aldosterone, the major hormone that regulates K+ secretion. In hypokalemic and
hyperkalemic conditions, the urinary excretion of K+ is low and high, respectively.
However, water reabsorption in the cortical and medullary collecting ducts is an
important determinant of urinary K+ concentration. For example, an increase in
water reabsorption increases and a decrease in water reabsorption decreases urine
[K+]. Therefore, an appropriate method to calculate urine [K+] is the transtubular K+
gradient (TTKG), which is calculated as follows:

U K POsm
TTKG = ,
PK U Osm

where UK and PK are urine and plasma K+ concentrations, respectively, and POsm and
UOsm are plasma and urine osmolalities, respectively. The urine to plasma osmolal-
ity ratio is used to correct the [K+] in the urine for the amount of water reabsorbed
in the distal nephron. TTKG is mostly useful in the evaluation of patients with hy-
perkalemia, but it can also be used in the evaluation of hypokalemia.
In normal subjects on a regular diet, the TTKG varies between 6 and 8. A TTKG
value < 57 in a patient with hyperkalemia indicates impaired distal tubular secre-
tion of K+ due to aldosterone deficiency or resistance. Patients with mineralocor-
ticoid excess should have a TTKG > 10. In a patient with hypokalemia, the distal
nephron should decrease the secretion of K+, and a TTKG value should be < 2.
Two assumptions must be met before using the TTKG formula: (1) there must be
adequate ADH activity, which is verified by measuring urine osmolality that should
exceed serum osmolality, and (2) there must be adequate delivery of filtrate to the
distal nephron for K+ secretion. This can be verified by determining urine Na+,
which should be > 25 mEq/L.

Urine Anion Gap

Urine anion gap (UAG) is an indirect measure of NH4+ excretion, which is not rou-
tinely determined in the clinical laboratory. However, it is measured by determining
16 2 Interpretation of Urine Electrolytes and Osmolality

the urine concentrations of Na+, K+, and Cl and is calculated as [Na+] + [K+] [Cl].
In general, NH4+ is excreted with Cl. A normal individual has a negative (from 0
to 50) UAG (Cl > Na+ + K+), suggesting adequate excretion of NH4+. On the other
hand, a positive (from 0 to+ 50) UAG (Na+ + K+ > Cl) indicates a defect in NH4+ ex-
cretion. The UAG is used clinically to distinguish primarily hyperchloremic metabol-
ic acidosis due to distal renal tubular acidosis (RTA) and diarrhea. Both conditions
cause normal anion gap metabolic acidosis and hypokalemia. Although the urine pH
is always > 6.5 in distal RTA, it is variable in patients with diarrhea because of un-
predictable volume changes. The UAG is always positive in patients with distal RTA,
indicating reduced NH4+ excretion, whereas, it is negative in patients with diarrhea
because these patients can excrete adequate amounts of NH4+. Also, positive UAG
is observed in acidoses that are characterized by low NH4+ excretion (type 4 RTA).
In situations such as diabetic ketoacidosis, NH4+ is excreted with ketones other
than Cl, resulting in decreased urinary [Cl]. This results in a positive rather than
a negative UAG, indicating decreased excretion of NH4+. Thus, the UAG may not be
that helpful in situations of ketonuria. Table 2.2 summarizes the interpretation of
urinary electrolytes in various pathophysiologic conditions.

Electrolyte-Free-Water Clearance

Electrolyte-free-water clearance (TeH2O) is the amount of water present in the urine

that is free of solutes, i.e., the amount of water excreted in the urine. Determination
of TeH2O is helpful in the assessment of serum [Na+] in hypernatremia and hypona-
tremia. For example, hypernatremia may not improve despite volume replacement
because the exact amount of free water that is reabsorbed or excreted is not known.
In order to quantify how much electrolyte-free-water is being reabsorbed or ex-
creted, the following formula can be used:

T e H2O = V
[U Na + UK ]
1,
[ PNa ]
where V is the total urine volume, and PNais the plasma [Na+]. TeH2O can be positive
or negative. Positive TeH2O means that less water was reabsorbed in the nephron seg-
ments, resulting in hypernatremia. On the other hand, negative TeH2O indicates that
the nephron segments reabsorbed more water with resultant hyponatremia.

Urine Specific Gravity Versus Urine Osmolality

Clinically, estimation of specific gravity is useful in the evaluation of urine concen-

tration and dilution. It is defined as the ratio of the weight of a solution to the weight
of an equal volume of water. The specific gravity of plasma is largely determined by
the protein concentration and to a lesser extent by the other solutes. For this reason,
Certain Pertinent Calculations 17

Table 2.2 Interpretations of urine electrolytes

Condition Electrolyte (mEq/L) Diagnostic possibilities
Hypovolemia Na+ (020) Extrarenal loss of Na+
Na+ (>20) Renal salt wasting
Adrenal insufficiency
Diuretic use or osmotic diuresis
Acute kidney injury Na+ (020) Prerenal azotemia
Na+ (>20) Acute tubular necrosis (ATN)
FENa (<1%) Prerenal azotemia
FENa (>2%) ATN due to contrast agent
Rhabdomyolysis
ATN
Diuretic use
Hyponatremia Na+ (020) Hypovolemia
Edematous disorders
Water intoxication
Na+ (>20) SIADH
Cerebral salt wasting (CSW)
Adrenal insufficiency
FEUA (>10%) SIADH and CSW
FEPO4 (>20%) CSW
Metabolic alkalosis Cl (010) Cl-responsive alkalosis
Cl (>20) Cl-resistant alkalosis
Hypokalemia K+ (010) Extrarenal loss of K+
K+ (>20) Renal loss of K+
TTKG
Normal 68
Hyperkalemia <5 Aldosterone deficiency or resistance
Hypokalemia <2 Appropriate distal tubular secretion
UAG Positive (from 0 to +50) Distal renal tubular acidosis
Negative (from 0 to 50) Diarrhea
TTKG transtubular K+ gradient, SIADH syndrome of inappropriate antidiuretic hormone

plasma is about 810% heavier than pure distilled water. Therefore, the specific
gravity of plasma varies from 1.008 to 1.010 compared to the specific gravity of
distilled water, which is 1.000. Urine specific gravity can range from 1.001 to 1.035.
A value of 1.005 or less indicates preservation of normal diluting ability and a value
of 1.020 or higher indicates normal concentrating ability of the kidney.
Osmolality measures only the number of particles present in a solution. On the
other hand, the specific gravity determines not only the number but also weight
of the particles in a solution. Urine specific gravity and urine osmolality usually
change in parallel. For example, a urine specific gravity of 1.0201.030 corresponds
to a urine osmolality of 8001,200mOsm/kgH2O. Similarly, the specific gravity of
1.005 is generally equated to an osmolality <100mOsm/kgH2O. This relationship
between the specific gravity and osmolality is disturbed when the urine contains
an abnormal solute, such as glucose or protein. As a result, the specific gravity
increases disproportionately to the osmolality. In addition to these substances, ra-
diocontrast material also increases the specific gravity disproportionately.
18 2 Interpretation of Urine Electrolytes and Osmolality

Table 2.3 Urine osmolalities in various clinical conditions

Condition Approximate osmolality Comment
(mOsm/KgH2O)
Normal 501200 Normal urine dilution and
concentration
AKI-Prerenal azotemia >400 Increased water reabsorption
by nephron segments
AKI-Acute tubular necrosis <400 Injured tubules cannot reab-
sorb all the filtered water
SIADH >200 Excess water reabsorption by
distal nephron
Hydrochlorothiazide treatment >200 Inability to dilute urine
Furosemide ~300 (isosthenuria) Inability to concentrate and
dilute urine
Osmotic diuresis >300 (usually urine Excretion of excess osmoles
osmolality>plasma
osmolality)
Central diabetes insipidus (DI) 100 Lack of ADH
Nephrogenic DI <300 ADH resistance
Psychogenic polydipsia ~50 Decreased medullary
hypertonicity
ADH Antidiuretic hormone, AKI acute kidney injury, SIADH syndrome of inappropriate antidi-
uretic hormone

Measurement of urine specific gravity or osmolality is useful in the assessment

of volume status, in the differential diagnosis of AKI, polyuria (urination of 35L/
day) and hyponatremia. A volume depleted individual with normal renal function is
able to concentrate his or her urine, and, therefore, the specific gravity or osmolal-
ity will be greater than 1.020 or 800mOsm/kgH2O, respectively. Table2.3 shows
approximate urine osmolalities in various clinical situations.

Study Questions

Case 1 A 60-year-old male patient with congestive heart failure (CHF) is admitted
for chest pain. He is on several medications, including a loop diuretic. The patient
develops acute kidney injury following cardiac catheterization with creatinine
increase from 1.5 to 3.5mg/dL. His urinalysis shows many renal tubular cells and
occasional renal tubular cell casts, suggesting ATN.
Question 1 What would his FENabe?
Answer In ATN, the FENashould be >2%. However, in a patient with CHF there
is increased Na+ reabsorption in the proximal tubule. Despite ATN, such a patient
excretes less Na+ in the urine and the FENais usually <1%. Other conditions of ATN
with low FENa(<1%) are contrast agents and rhabdomyolysis.
Suggested Reading 19

Question 2 How does FEurea help in this patient?

Answer The patient is on a loop diuretic. In order to know the volume status in
a patient on diuretic, FENa may not be that helpful. Instead, FEureadistinguishes
volume contraction from volume expansion. In volume contracted patient due to
diuretics, FEurea is <35%.
Case 2 A 20-year-old female patient is admitted for weakness, dizziness, and fati-
gue. Her serum K+ is 2.8mEq/L and HCO3 is 15mEq/L. An arterial blood gas
revealed a nonanion gap metabolic acidosis. Her urine pH is 6.5.
Question 1 Discuss the clinical application of UAG?
Answer Two major causes of nonanion gap metabolic acidosis with hypokalemia
are diarrhea and distal RTA. The urine pH is always >6.5 in distal RTA and mostly
acidic in diarrhea unless the patient is severely volume depleted. In this patient,
determination of the UAG will distinguish diarrhea from distal RTA.
The UAG is an indirect measure of NH4+ excretion. It is calculated as the sum of
urinary [Na+] plus [K+] minus [Cl]. Normal UAG is zero to negative, suggesting ad-
equate excretion of NH4+. In patients with distal RTA, NH4+ excretion is decreased,
and the UAG is always positive. In metabolic acidosis caused by diarrhea, the UAG
is negative. Thus, the UAG is helpful in the differential diagnosis of hyperchloremic
metabolic acidosis. Upon questioning, the patient admitted to laxative abuse.
Case 3 A 32-year-old diabetic male patient presents to his primary care physician
with persistent hyperkalemia. His glucose is 100mg/dL. He is not on any K+-
sparing diuretic. Electrocardiography (EKG) does not show any changes consistent
with hyperkalemia. His TTKG is 6.
Question 1 How does TTKG help in the evaluation of hyperkalemia in this patient?
Answer In general, hyperkalemia stimulates the release of aldosterone, which in
turn promotes the secretion of K+ in the distal nephron, leading to a TTKG value
>10 in a normal individual. This suggests that the function of aldosterone is intact.
In this patient, the TTKG is 6, suggesting that he has either hypoaldosteronism or
aldosterone resistance.

Suggested Reading

1. Choi MJ, Ziyadeh FN. The utility of the transtubular potassium gradient in the evaluation of
hyperkalemia. J Am Soc Nephrol. 2008;19:4246.
2. Harrington JT, Cohen JJ. Measurement of urinary electrolytes-indications and limitations. N
Engl J Med. 1975;293:12413.
3. Kamel KS, Ethier JH, Richardson RMA, etal. Urine electrolytes and osmolality: when and
how to use them. Am J Nephrol. 1990;10:89102.
4. Schrier RW. Diagnostic value of urinary sodium, chloride, urea, and flow. J Am Soc Nephrol.
2011;22:161013.
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