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Polyuria in Childhood

Alexander K.C. Leung, MBBS, FRCPC, FRCPI, FRCP(Glasg), FRCP(Edin)*;

Wm. Lane M. Robson, MD, FRCPC*;
Mitchell L. Halperin, MD, FRCPC**

Polyuria may result from either a water or a solute diuresis. Although the history and
physical examination may provide clues to the cause of the polyuria, the definitive diagnosis
requires laboratory tests which focus on the osmolality of the urine and serum in combination
with the urine volume and the rate of excretion of osmoles. An isoosmolar or hyperosmolar
urine is found in children with a solute diuresis or in normal children, whereas a hypoosmolar
urine is found in children with a water diuresis. In the latter case, a low serum osmolality
suggests primary polydipsia whereas a high serum osmolality suggests antidiuretic hormone
(ADH) deficiency or insensitivity. A water deprivation test is necessary when the initial
evaluation fails to establish the cause of polyuria. A vasopressin test enables the differentia-
tion between neurogenic and nephrogenic diabetes insipidus (DI).

Introduction sodium in the thin ascending loop of Henle, active sodium

The traditional definition of polyuria, or excessive urinary chloride transport in the thick ascending loop of Henle (cortical
volume, concerns only the volume of urine and is defined as the and medullary segments), urea reabsorption in the collecting
production of greater than 900 ml of urine/m2/day.’ This defini- tubule, and an intact vasa recta to prevent &dquo;wash-out&dquo; of this
tion is too restrictive and should be expanded to include any regional hyperosmolality.1 ADH acts on the cortical and medul-
situation when the urine output is inappropriately high relative to lary collecting tubules to permit the absorption of water. ADH
the effective circulating volume and the concentration of sodium binds to a specific receptor on the basolateral membrane of these
in plasma, regardless of the actual volume of urine.2 cells and increases the activity of adenyl cyclase which generates
Polyuria is usually associated with an underlying neurological, cyclic AMP.3 Cyclic AMP activates a protein kinase. Microtu-
renal, or metabolic disorder and may result in severe contraction bule and microfilament formation occurs and results in an in-
of extracellular fluid (ECF) or intracellular fluid (ICF) volumes. crease in the permeability of water in the luminal membrane,
The purpose of this article is to review the causes of polyuria and perhaps by increasing the number of aqueous pores. If a child has
offer a physiologic approach to the evaluation and management of a limited ability to concentrate the urine, the volume of urine is
this clinical finding. determined primarily by the load of solutes that must be excreted.
For example, in a child who has a maximum ability to concentrate
Physiology the urine to 500 mOsm/kg, the urine volume with solute loads of
The volume of urine depends upon the amount of solute and 250 mOsm, 500 mOsm and 1000 mOsm would be 500 ml, 1000
water ingested or produced by metabolism in excess of needs and ml and 2000 ml, respectively.
the ability to concentrate ordilute the urine. The ability to
concentrate the urine depends on the presence of ADH and a Etiology
hyperosmolar medullary interstitium. To achieve this high osmo- Polyuria may result from either a water diuresis or a solute
lality, there must be an intact countercurrent multiplier system. diuresis (Table 1).
This, in turn, requires the presence of a water permeable segment A water diuresis may be due to either primary polydipsia or
in the thin descending loop of Henle, passive reabsorption of diabetes insipidus. Primary polydipsia may be due to compulsive
water drinking, treatment with large quantities of water, or a
defect in the thirst center.’ Compulsive water drinking is rare in
children. The disorder occurs most commonly in adolescents or
adults who have a significant psychological disturbance. Large
From the *Department of Pediatrics, the University of Calgary and the volumes of water may be prescribed for children in clinical
**Department of Medicine, the University of Toronto. situations, such as the treatment of nephrolithiasis, or with drugs,
Correspondence to: Dr. Alexander K.C. Leung, Alberta Children’s Hospi- such as cyclophosphamide. Infants who are given milk or fluid as
tal, 1820 Richmond Road SW, Calgary, Alberta, Canada T2T 5C7. a pacifier may also have polyuria. Thirst center defects may be


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in the
primary or may develop as a consequence of a lesion Table 1. Causes of polyuria in childhood.
hypothalamus of the central nervous system (CNS).~
Diabetes insipidus (DI) is due to either failure of the neurohy-
pophysis to synthesize or secrete adequate quantities of ADH
(neurogenic DI) or failure of the kidney to respond appropriately
tocirculating ADH (nephrogenic DI).
Neurogenic DI results from a spectrum of deficiencies that may
produce mild, partial defects to complete absence of ADH and
may be either primary or secondary to a number of disorders.
Primary neurogenic DI may become evident at any age, and in the
majority of children is sporadic. The uncommon familial forms
occur as either an autosomal dominant or an X-linked recessive
condition.1,5 Secondary neurogenic DI is more common and may
result from any lesion that damages the neurohypophyseal sys-
tem. The possible causes of neurogenic DI are listed in Table 1.
Nephrogenic DI may be either congenital or acquired. The
congenital form is transmitted as an X-linked recessive trait.’I
Acquired nephrogenic DI is more common than the congenital
form. The potential causes are listed in Table 1. We prefer to think
of the causes of nephrogenic DI in two categories, those involving
the cortex and those primarily involving the medulla. The former
lead to very large volumes of urine since the osmolality of urine is
less than that of plasma. In contrast, when the medulla is the primary
site of involvement, ADH acts and the osmolality of fluid in the
lumen of the cortical collecting duct rises to that of plasma. Hence
the osmolality of the urine is close to 300 mOsm/kg H20 and the
volume of urine now dcpends on the load of osmoles to excrete.
This form of nephrogenic DI is more of an inconvenience rather
than a specific threat to the patient, but it may signal the presence of
a variety of disorders (Table 1). The differentiation of those cases

of nephrogenic DI, where the primary site of the lesion is in the

cortex as compared to the medulla, may be accomplished by
examining the urine osmolality. If this value is distinctly below that
of the plasma (<200 mOsm/kg), the cortical distal nephron is
involved. In contrast, a urine osmolality of approximately 300
mOsm/kg suggests that the predominant lesion is in the medulla
such as occurs with interstitial disease or structural damage.
A solute diuresis may be due to the accumulation of either
organic or inorganic solutes in the urine. The common organic
solutes which may cause a diuresis are glucose and urea.2 The
inorganic solutes include sodium, potassium, and possibly am-
monium salts where the anion is usually chloride or bicarbonate.

Differential Diagnosis
Polyuria should be differentiated from small-volume urinary
frequency. Polyuria is almost always associated with increased
frequency of urination, whereas increased urinary frequency is not
always associated with polyuria. True polyuria is usually associated
with polydipsia, whereas small-volume urinary frequency is not.
Increased urinary frequency may be secondary to cystitis,
urethritis, urethral irritation from chemical agents, such as bubble
bath, urethral obstruction, or urethral trauma consequent to cath-
eterization, masturbation, sexual abuse, or straddle injuries.
The daytime urinary frequency syndrome presents in healthy
children, usually boys, who develop daytime frequency of up to
20-40 times a day and in whom a known organic cause has been
excluded.6-8 Dysuria and enuresis are uncommon. The condition


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isusually self-limiting, with the frequency subsiding spontane- Thirst invariably occurs in association with polyuria except in
ously in less than three months. those situations secondary to iatrogenic fluid or solute overload. In
the majority of children with neurogenic or nephrogenic DI, thirst,
Clinical Evaluation particularly for cold water, is intense.9 In contrast, the preference for
The presenting symptom of polyuria is voiding larger quantities cold water is not a feature of primary polydipsia or a solute diuresis.
of urine than the child has previously experienced. In infancy, the The history may suggest clues to the cause of the polyuria (Table
presenting feature may be frequent wet and excessively heavy 2). Table 3 lists the specific features on physical examination which
diapers. Infants may be irritable or cry excessively due to are helpful in the assessment of a child with polyuria. An assessment
unrelieved thirst. Older children may present with enuresis. The of the ECF volume is important since ECF volume contraction may
absence of enuresis or nocturia in the presence of polyuria result from the loss of sodium and chloride during the polyuria.
suggests an excessive fluid intake such as occurs with primary Children with polyuria due to primary polydipsia or a sodium
polydipsia. The onset of compulsive water drinking is typically chloride load present with a normal ECF volume whereas polyuria
more gradual than in DI. When frequency is secondary to due to an osmotic diuresis usually presents with a reduced ECF
polyuria, the patient presents with complaints of copious volumes volume.
of pale, water-like urine, whereas when frequency is unrelated to
polyuria, the volume of urine is low. If the diagnosis is in doubt, Laboratory Investigations
a 24-hour collection of urine may be necessary to establish the
Figure 1 outlines an approach to the investigation of the child with
diagnosis. A good assessment of the completeness of a 24-hour polyuria. The osmolality and timed volume of the urine should be
urine collection is to measure the urine creatinine which should be determined. From these two numbers, an estimate of the rate of
at least 15 mg (130 pool) creatinine/kg/day. excretion of osmoles can be obtained.

Table 2. Historical information in the evaluation of polyuria.


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Table 3. Physical examination findings in the evaluation of polyuria.

The specific gravity (SG) of a first morning urine sample is a child should be denied access to food or fluid. The child is
useful screening test of renal concentrating ability. Urine osmo- weighed hourly, and each voided urine sample measured for
lality is more reliable than the SG since the SG may be volume and osmolality. At the end of the study period, the initial
disproportionally affected by the presence of protein, glucose or blood tests are repeated. If the body weight falls by more than
radiocontrast dye in the urine. A first morning urine SG of greater 3%, the test should be terminated after obtaining the final blood
than 1.010 or a urine osmolality greater than 400 mOsm/kg is studies. The response to a water deprivation test may be
found in children with a solute diuresis or in normal children, interpreted as shown in Table 4.
whereas a urine SG less than 1.005 or a urine osmolality less than Once the diagnosis of DI is established, it is possible to
200 mOsm/kg indicates a water diuresis.’1 distinguish neurogenic DI from nephrogenic DI with a vaso-
A urinalysis may show cellular elements which suggest a pressin (ADH) test. At the end of the water deprivation test, the
parenchymal disorder, or glucosuria and ketonuria which suggest child is given 6 U of aqueous vasopressin per M2 subcutaneously
diabetes mellitus. , or 20 pg of l-desamino-8-D-arginine vasopressin (DDAVP)
The serum potassium, calcium, glucose, creatinine, and urea intranasally, and is allowed free access to water. In children
may provide evidence for the presence of disorders listed in Table with neurogenic DI, a reduction in urine output and a subsequent
1. A low serum osmolality in a child with hypoosmolar urine increase in urine osmolality will ensue (Table 4). Children with
suggests primary polydipsia as the most likely cause. A high nephrogenic DI will not show a normal response. Both neuro-
serum osmolality suggests DI, hyperglycemia, or an elevated genic and nephrogenic DI can be partial, in which case the
concentration of urea. If the
serum glucose and urea are normal, children will show some increase in urine osmolality during
a high serum osmolality suggests a deficiency or insensitivity to ECF volume contraction, and will have an additional increase
ADH. after vasopressin administration, but the values will not be
A water deprivation test is a simple procedure to determine appropriate for the state of hydration or hyperosmolality.1 Par-
the ability of a child to concentrate the urine in response to serum tial defects of neurogenic or nephrogenic DI may be more
hyperosmolality and ECF volume contraction, both of which accurately diagnosed by measurements of ADH concentrations
are stimuli for ADH production. The test should be carried out in plasma during the water deprivation test (Table 4).5,11 This
if the initial evaluation fails to establish the cause of polyuria. It measurement of ADH is especially useful in very young chil-
should not be performed in a patient with hypernatremia. The dren in whom the water deprivation test is difficult to perform
test should be done under close supervision since children with and the normal range of urine osmolality in response to water
compulsive water drinking may go to great lengths to obtain deprivation is broad. Plasma ADH concentrations should be
water, while those with DI may rapidly develop ICF volume interpreted with caution since numerous non-osmotic stimuli,
contraction. After a 24-hour period of adequate hydration, such as nausea, fear, and anxiety, can lead to transient increases
blood is drawn to determine the serum sodium concentration in ADH.
and osmolality. The urine osmolality and volume are measured, Children with neurogenic DI require a skull roentgenogram,
the child is weighed, and the urine output recorded.’ Most tests computed tomographic scan or magnetic resonance imaging of
are conducted for six to eight hours. During the study period, the the brain, and pituitary function tests such as determination of


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Figure 1. The differentiation of the causes of polyuria.


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Table 4. Normal and abnormal responses to water deprivation and ADH administration.

growth hormone, thyrotropin, adrenocorticotropin, luteinizing hor- concentration and osmolality each week initially, with decreasing
mone, and follicle-stimulating hormone. In nephrogenic DI, an frequency thereafter, and at least every three months once stable, to
ultrasonographic examination of the kidneys and collecting system ensure that the dose is appropriate.
should be performed to look for urinary obstruction. A voiding Diuretics such as hydrochlorothiazide, 1-2 mg/kg/day, and di-
cystourethrogram may be indicated if there is a history to suggest etary salt restriction, may be helpful in nephrogenic DI to lower the
urethral obstruction or vesicoureteric reflux. volume of urine (at the price of a contracted ECF volume). Main-
taining the child in a state of mild ECF volume contraction enhances
Management reabsorption of sodium chloride and water and thus minimizes the
Any underlying disease should be recognized and treated. Cor- polyuria. Hypokalemia should be prevented by increasing dietary
rection of hypokalemia or hypercalcemia, treatment of diabetes potassium intake.
mellitus or an underlying renal disease, and discontinuation of an Compulsive water drinking is rare in children and presents a
offending drug may result in resolution of polyuria.9 Children with formidable therapeutic challenge. Appropriate psychotherapy is
DI should be allowed free access to fluids to prevent severe usually required to control the compulsive drinking.
contraction of the ICF. ECF volume contraction may result from the polyuria of an
In neurogenic DI, replacement therapy with ADH or its analogue, osmotic diuresis and requires treatment with sodium chloride, given
arginine vasopressin, produces a satisfactory response in virtually at a rate such that a positive balance for sodium occurs and the ECF
all children. DDAVP, at a dosage range of 5 to 20 pg intranasally, volume returns to normal. Sufficient water must be given to ensure
once or twice a day, is highly effective.9,12 The dose should be that the serum sodium concentration does not rise appreciably.
individualized according to the renal response. If the drug is given
only once a day, the evening is preferred to avoid nocturia. DDAVP Summary
has fewer pressor effects than ADH and the antidiuretic effect is Polyuria in childhood usually indicates an underlying neurologi-
maintained. It has a relatively long duration of action, and absorp- cal, renal or metabolic disorder. The diagnosis may be established
tion from the nasal mucosa is excellent Excess nasal mucus due by examination of the osmolality of urine and serum, the volume of
to allergic or infectious rhinitis may, however, interfere with the urine, and the rate of excretion of osmoles. The treatment should be
absorption of DDAVP.’3 Although side effects are uncommon, directed to correct the underlying physiologic abnormality.
headache and hypertension due to water retention have been re-
ported due to excessive water intake and more prolonged action due
to large dosages (40ug).’~ Vasopressin tannate in oil, two to five
units intramuscularly, every 24 to 72 hours, may also be used. &dquo;9 It The authors would like to thank Ms. Kathy Campbell-Brown
is important to monitor the weight of the child and serum sodium and Ms. Michelle Drew for their expert secretarial help and Mr.


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Sulakhan Chopra of the University of Calgary medical library for
his assistance in the preparation of the manuscript.

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