BJU International (1999), 84, Suppl.

1, 1719

Nocturnal polyuria
G. R OBERT SON
Northwestern University Medical School, Chicago, USA

Keywords Nocturia, nocturnal enuresis, polyuria, urine production, solutes, arginine vasopressin, diabetes

Introduction
The rate of urine production is determined by two
processes; the concentration of urine and the rate of
solute excretion. Urine concentration is controlled by the
antidiuretic hormone, arginine vasopressin (AVP) which
acts upon the distal and collecting tubules of the kidney
to increase the amount of solute free water reabsorbed
from the glomerular filtrate. Urinary solute is composed
largely of urea, sodium, potassium and chloride; the rate
of excretion of these solutes varies depending upon the
diet and other factors that influence protein metabolism
and extracellular fluid volume.
Polyuria is a condition characterized by the excretion
of an excessively large volume of urine over 24 h. The
upper limit of normal has not been fully defined but is
probably about 40 mL/kg body weight per day. Higher
rates of output can be caused by a solute diuresis, such
as the glucosuria that occurs in patients with uncontrolled diabetes mellitus, or by inadequate concentration
of the urine, as in patients with diabetes insipidus (DI).
DI can be divided into three categories, each with a
diCerent cause: the most common type arises from a
deficiency in AVP and is called pituitary or central DI;
the second type, termed nephrogenic DI, results from
renal resistance to the antidiuretic eCect of AVP; and a
third type, termed primary polydipsia, is caused by an
excessive intake of fluids. The polydipsia can result from
psychological/cognitive defects, in which case it is called
psychogenic polydipsia, or it can be caused by a primary
abnormality in the thirst mechanism, which has been
referred to as dipsogenic DI.
Nocturnal polyuria (NP) refers to a condition in which
the rate of urine output is excessive only at night; the
total 24-h output is within normal limits. The aim of this
review is to discuss briefly the definitions, causes and
clinical consequences of NP. A fuller discussion of these
and related issues can be found in a recent review [1].

Defining nocturnal polyuria

An accurate and generally accepted definition of NP is
a prerequisite for any meaningful discussion of its
1999 BJU International

clinical significance (see van Kerrebroeck and Weiss,

page 14. Several diCerent definitions have been suggested and used by diCerent investigators. One is the
amount of urine produced at night expressed as a
percentage of the total 24-h urine volume. As the mean
time spent asleep is about a third of the day (an
arbitrary 8 h) overnight urine output exceeding 35%
of the total has been used an indication of NP [2].
However, this definition may be too generous, as circadian studies indicate that the rate of urine production
during sleep is normally about half to two-thirds of that
during waking hours [3]. Moreover, defining NP as a
percentage of total urine output would exclude the
severe NP that occurs in patients with DI and could
over-diagnose it in patients with unusually low total
urine outputs. Also it does not take into account
variations in the duration of sleep. Thus others have
defined NP in terms of nocturnal urine volume per unit
time, with the upper limit of normal being 0.9 mL/min
[4]. However, this approach fails to consider variations
in body size and hence the most useful approach may
be one that defines NP in terms of the rate of urine
output per unit of body size. In one recent study
involving healthy young adults, the upper limit of
normal urine output during sleep was 1 mL/h/kg
[3]. It is not known if this value varies with age and
gender.
The latter definition does not take into account
individual diCerences in functional bladder capacity,
which can also aCect the frequency of urination.
Therefore a separate measure, termed the nocturia
index [5] also has been used to express nocturnal urine
output as a function of bladder capacity. As would be
expected, this index appears to be a better predictor of
the severity of nocturia. However, it is not a suitable
definition for nocturnal polyuria because it does not
distinguish increases in the rate of urine output from
reductions in bladder capacity.
However NP is defined, it appears to play a significant
role in the pathogenesis of two syndromes, nocturnal
enuresis and nocturia, that also may be associated with
defects in the lower urinary tract.

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G. R OBERT SON

Nocturnal enuresis
Nocturnal enuresis is characterized by the involuntary
passage of urine at night during sleep [6], and is
discussed in detail by Djurhuus (this supplement, page
912). It can exist as either primary or secondary
enuresis (bed-wetting returning after an absence of at
least 6 months) and range in severity from a few times
a month to several times a night. Enuresis is very
common (almost the rule) in young children, but it can
also persist into adolescence and adulthood in a small
percentage (12%) of the population [7], where it
may cause severe emotional distress and social
maladjustment.
The causes of nocturnal enuresis have been debated
for a long time [6]. In some cases it appears to be caused
by defects in bladder function. In others, it has been
attributed to disturbances in sleep or emotional maladjustment, but convincing evidence for these links is still
lacking [8]. However, a link between nocturnal enuresis
and NP [9] has now been clearly established [10].
The NP in patients with enuresis appears to be multifactorial in that it can be caused by a solute diuresis, a
water diuresis or both. When present, the solute diuresis
seems to arise largely by increased excretion of sodium
and its associated anions at night. In children, the water
diuresis appears to result from a deficiency in the normal
nocturnal increase in AVP secretion. However, in adults
AVP secretion normally does not increase at night and
the nocturnal water diuresis associated with nocturnal
enuresis appears to be largely ascribable to renal resistance to the antidiuretic eCect of AVP [3]. The causes of
these circadian defects in sodium excretion, AVP
secretion or AVP action have not been determined.
NP cannot be the only factor responsible for enuresis
as adults with DI excrete very large volumes of urine
overnight but usually have nocturia rather than
enuresis. This suggests that there must be one or more
additional defects, possibly in arousal or bladder control,
which are necessary for enuresis to occur in children
and some adults. Recent evidence suggests that a genetic
component may also be involved in the pathogenesis of
enuresis [11] but the mechanism and the gene or genes
involved are unknown.

Nocturia
Nocturia is defined as waking at night to void. The
fundamental diCerence between nocturia and enuresis is
that, while the latter involves involuntary voiding, people
with nocturia awaken to void voluntarily. Otherwise,
they are remarkably similar. As with enuresis, nocturia
has a multifactorial aetiology, including outlet obstruction of the lower urinary tract, deterioration of the CNS

and/or bladder instability [12,13]. The prevalence of

nocturia also varies with age but in this case it increases
in adults as they age [14]. Outlet obstruction of the
lower urinary tract has often been attributed to BPH but
this obviously cannot be a factor in women, who have
an incidence of nocturia similar to that in men.
A more important pathogenic factor common to nocturia in both sexes may be NP. As in enuresis, the NP
in nocturics can be caused by a solute diuresis, a water
diuresis or both [15]. The pathogenic mechanisms
involved are still controversial and may involve a variety
of factors, including excess retention of salt and water
then upright during the day, followed by a compensatory
natriuresis when recumbent at night, and defects in the
secretion and/or action of AVP similar to those observed
in enuretic children [1618]. In any event, NP should
not be overlooked or dismissed as a possible aetiological
factor in nocturia, even in men presenting with symptoms suggestive of BPH.

Conclusion
Further studies are needed to define the role of NP in
the pathogenesis of enuresis and nocturia. These studies
should include a better definition of the eCect of age and
gender on the normal circadian patterns of solute and
water excretion. This information may lead to the application of treatments that are simpler and more eCective
than those currently used to treat enuresis and nocturia.

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Author
G.

Robertson, MD, Professor Medicine and Urology,

Northwestern University Medical School, Chicago, USA.