BJU International (1999), 84, Suppl. 1, 1719Nocturnal polyuriaG. ROBERTSONNorthwestern University Medical School, Chicago, USAKeywords Nocturia, nocturnal enuresis, polyuria, urine production, solutes, arginine vasopressin, diabetesclinical signicance (see vanKerrebroeckandWeiss,Introductionpage14. Several diCerentdenitionshavebeensug-gestedandusedbydiCerent investigators. Oneisthe The rate of urine production is determined by twoprocesses; the concentrationof urine andthe rate of amount of urine produced at night expressed as apercentage of the total 24-h urine volume. As the mean solute excretion. Urine concentration is controlled by theantidiuretic hormone, arginine vasopressin (AVP) which time spent asleep is about a third of the day (anarbitrary8 h) overnight urineoutput exceeding35% acts upon the distal and collecting tubules of the kidneytoincreasetheamountof solutefreewaterreabsorbed of the total has beenused anindicationof NP[2].However, this denition may be too generous, as circad- from the glomerular ltrate. Urinary solute is composedlargely of urea, sodium, potassium and chloride; the rate ianstudies indicatethat therateof urineproductionduring sleep is normally about half to two-thirds of that of excretionof thesesolutesvariesdependinguponthediet and other factors that inuence protein metabolism duringwakinghours[3]. Moreover, deningNPasapercentage of total urine output would exclude the and extracellular uid volume.Polyuria is a condition characterized by the excretion severeNPthat occurs inpatients withDI andcouldover-diagnoseit inpatients withunusuallylowtotal of anexcessivelylargevolumeof urineover24 h. Theupperlimitof normal hasnotbeenfullydenedbutis urine outputs. Also it does not take into accountvariationsinthedurationof sleep. Thusothershave probablyabout40 mL/kgbodyweightperday. Higherrates of output can be caused by a solute diuresis, such dened NP in terms of nocturnal urine volume per unittime, with the upper limit of normal being 0.9 mL/min astheglucosuriathat occurs inpatients withuncon-trolled diabetes mellitus, or by inadequate concentration [4]. However, this approach fails to consider variationsinbodysizeandhencethemostuseful approachmay oftheurine,asinpatientswithdiabetesinsipidus(DI).DI canbe dividedinto three categories, eachwitha beonethat denes NPinterms of therateof urineoutput per unit of body size. In one recent study diCerent cause: the most commontype arises fromadeciency in AVP and is called pituitaryor central DI; involving healthy young adults, the upper limit ofnormal urine output during sleep was 1 mL/h/kg the secondtype, termednephrogenic DI, results fromrenalresistancetotheantidiureticeCectofAVP;anda [3]. Itisnot knownif thisvaluevarieswithageandgender. thirdtype, termedprimarypolydipsia, iscausedbyanexcessive intake of uids. The polydipsia can result from The latter denition does not take into accountindividual diCerences infunctional bladder capacity, psychological/cognitive defects, in which case it is calledpsychogenic polydipsia, or it can be caused by a primary which can also aCect the frequency of urination.Therefore a separate measure, termed the nocturia abnormalityinthethirst mechanism, whichhasbeenreferred to as dipsogenic DI. index [5] also has been used to express nocturnal urineoutputasafunctionof bladdercapacity. Aswouldbe Nocturnal polyuria (NP) refers to a condition in whichtherateof urineoutput isexcessiveonlyat night; the expected,thisindexappearstobeabetterpredictoroftheseverityof nocturia. However, it isnot asuitable total 24-h output is within normal limits. The aim of thisreviewis todiscuss brieythe denitions, causes and denitionfor nocturnal polyuriabecause it does notdistinguishincreasesintherateof urineoutput from clinicalconsequencesofNP. Afullerdiscussionof theseand related issues can be found in a recent review [1]. reductions in bladder capacity.However NP is dened, it appears to play a signicantroleinthepathogenesisof twosyndromes, nocturnalDening nocturnal polyuriaenuresis and nocturia, that also may be associated withdefects in the lower urinary tract. Anaccurate andgenerally accepted denition of NP isa prerequisite for any meaningful discussion of its17 1999 BJU International18 G. ROBERTSONand/or bladder instability [12,13]. The prevalence ofNocturnal enuresisnocturia also varies with age but in this case it increasesinadults as they age [14]. Outlet obstructionof the Nocturnal enuresisischaracterizedbytheinvoluntarypassage of urine at night during sleep [6], and is lower urinary tract has often been attributed to BPH butthisobviouslycannotbeafactorinwomen,whohave discussedindetail byDjurhuus(thissupplement, page912). It can exist as either primary or secondary an incidence of nocturia similar to that in men.A more important pathogenic factor common to noc- enuresis (bed-wettingreturningafter anabsenceof atleast6 months) andrange in severityfroma fewtimes turiainbothsexesmaybeNP. Asinenuresis, theNPin nocturics can be caused by a solute diuresis, a water a month to several times a night. Enuresis is verycommon (almost the rule) in young children, but it can diuresis or both [15]. The pathogenic mechanismsinvolved are still controversial and may involve a variety alsopersist intoadolescenceandadulthoodinasmallpercentage (12%) of the population [7], where it of factors, includingexcessretentionof salt andwaterthen upright during the day, followed by a compensatory may cause severe emotional distress and socialmaladjustment. natriuresis when recumbent at night, and defects in thesecretion and/or action of AVP similar to those observed Thecauses of nocturnal enuresishavebeendebatedfor a long time [6]. In some cases it appears to be caused inenureticchildren[1618]. Inanyevent, NPshouldnot be overlooked or dismissed as a possible aetiological by defects inbladder function. Inothers, it has beenattributed to disturbances in sleep or emotional maladjust- factorinnocturia, eveninmenpresentingwithsymp-toms suggestive of BPH. ment, but convincing evidence for these links is stilllacking [8].However,a linkbetween nocturnalenuresisand NP [9] has now been clearly established [10].ConclusionThe NP in patients with enuresis appears to be multi-factorial inthatit canbe causedby asolutediuresis,a Furtherstudiesareneededtodenetheroleof NPinthe pathogenesis of enuresis and nocturia. These studies water diuresis or both. When present, the solute diuresisseemstoariselargelybyincreasedexcretionof sodium should include a better denition of the eCect of age andgenderonthenormal circadianpatternsof soluteand and its associated anions at night. In children, the waterdiuresis appears to result from a deciency in the normal water excretion. This information may lead to the appli-cation of treatments that are simpler and more eCective nocturnal increase in AVP secretion. However, in adultsAVPsecretionnormallydoesnotincreaseatnightand than those currently used to treat enuresis and nocturia.thenocturnal waterdiuresisassociatedwithnocturnalenuresis appears tobelargely ascribable torenalresist-ance to the antidiuretic eCect of AVP [3]. The causes ofReferencesthese circadian defects in sodium excretion, AVP1RobertsonGR, RembrattA, AnderssonK-E. Desmopressinsecretion or AVP action have not been determined.inthetreatment of disordersof urineoutput inhumans.NP cannot be the onlyfactor responsible for enuresis1999; JAMA 1999; in pressasadults withDI excreteverylargevolumesof urine2SaitoM, KondoA, KatoT, YamadaY. Frequency-volumeovernight but usually have nocturia rather thancharts comparisonoffrequency betweenelderly and adultenuresis.Thissuggests thattheremustbeoneormorepatients. Br J Urol 1993; 72: 3841additional defects, possibly in arousal or bladder control,3Rittig S, Kovacs L, Gaskill MB et al. Adult nocturnalwhicharenecessaryfor enuresis tooccur inchildrenenuresis: acircadiandefect infree water excretion. Clinand some adults. Recent evidence suggests that a geneticRes 1993; 41: 666Acomponent may also be involved in the pathogenesis of4Asplund R, Sundberg B, Bengtsson P. Desmopressin for thetreatment of nocturnal polyuria inthe elderly: a dose- enuresis [11] but the mechanism and the gene or genestitration study. Br J Urol 1998; 82: 6426involved are unknown.5WeissJP, StemberDS, ChaikinDC, BlaivasJG. Evaluationof the etiology of nocturia in men: the nocturia andNocturianocturnal bladder capacity indices. Neurourol Urodyn 1999;in pressNocturia is dened as waking at night to void. The6Norgaard JP. Pathophysiology of nocturnal enuresis. Scandfundamental diCerence between nocturia and enuresis isJ Urolo Nephrol Suppl 1991; 140: 135that, while the latter involves involuntary voiding, people7Burgio KL, Locher JL, Ives DG. Nocturnal enuresis inwithnocturiaawakentovoidvoluntarily. Otherwise,community dwelling older adults. J Am Geriatrics Soc 1996;they are remarkably similar. As with enuresis, nocturia44: 13943hasamultifactorialaetiology, includingoutletobstruc- 8Kramer NR, Bonitati AE, Millman RP. Enuresis andobstructive sleep apnea in adults. Chest 1998; 114: 6347 tion of the lower urinary tract, deterioration of the CNS 1999 BJU International 84, Suppl. 1, 1719NOCTURNALPOLYURIA 199PoultonEM. Relative nocturnal polyuria as a factor in JC. Nocturnal polyuria and natriuresis inmale patientswithnocturiaandlower urinarytract symptoms. J Urol enuresis. Lancet 1952; 2: 906710Rittig S, Knudsen UB, Norgaard JP et al. Abnormal diurnal 1996; 156: 12929916AsplundR, AbergHE. 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Robertson, MD, Professor Medicine and Urology,Northwestern University Medical School, Chicago, USA. 15MatthiesenTB, RittigS, NrgaardPedersenEB, Djurhuus 1999 BJU International 84, Suppl. 1, 1719