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Evaluationofproteinuria
SanaWaheed,MD
Overview Acknowledgements
Differential
LastUpdated:20160729

Urgentconsiderationsexistforthiscondition,clicktoview Diagnosis
Averagedailyurinaryproteinexcretioninadultsis80mg/day,withnormalexcretionconsideredtobe<150 Sortby:category|common/uncommon
mg/day.Albuminrepresentsapproximately15%ofthedailyurinaryproteinexcretioninhealthypeople,with
otherplasmaproteins(e.g.,immunoglobulins,beta2microglobulin)andTammHorsfallproteinconstituting Transient
theremaining85%.Proteinuriavariesinamountandmaybetransientorpersistent. [1] [2] Fever
Urinaryexcretionofabnormalquantitiesofproteinfor3months,withorwithoutadecreaseinglomerular
Heavyphysicalexertion
filtrationrate(GFR),isdiagnosticofchronickidneydisease. [3] [4]
Urinarytractinfection
Urinealbuminmeasurementisanimportantcomponentinscreeningforchronickidneydisease.The
presenceofproteinuriaisanindependentriskfactorforcardiovasculardisease,death,andendstagerenal Urologichemorrhage
diseaseinthegeneralpopulation,andinpatientswithchronickidneydisease. [5] [6] [7] [8] [9] Presenceof
proteinuriaisassociatedwithahighermortalityincriticallyillpatients [10] [11] thedegreeofproteinuriapost Orthostaticproteinuria
renaltransplantationispredictiveofgraftandpatientsurvival. [12] Pregnancy
Reductionofproteinuriabypharmacologictherapyisusedasasurrogatemarkerinthemanagementof Glomerulardisease
chronickidneydiseaseandmanyacuteglomerulardiseasesandisassociatedwithimprovedrenal
outcomes. [13] [14] [15] [16] [17] [18] [19] Minimalchangedisease
Focalsegmental
Proteinuriadefinitions glomerulosclerosis
Membranousnephropathy
Eithertotalurineproteinorjustthealbuminfractioncanbemeasured.Urinealbuminmeasurementsare
bettervalidatedinregardtoassociationwithriskforchronickidneydiseaseprogressionandcardiovascular Membranoproliferative
events. glomerulonephritis
Albuminuria IgAnephropathy
Albuminuriaisgradedasfollows: [20] Systemiclupuserythematosus
A1(normaltomildlyincreasedalbuminuria) Postinfectious
glomerulonephritis
Albuminexcretionrate:<30mg/24hours.
Amyloidosis
Albumintocreatinineratio(ACR):<30mg/g.
Lightandheavychain
A2(moderatelyincreasedalbuminuria) depositiondiseases
Albuminexcretionrate:30300mg/24hours. Fibrillaryandimmunotactoid
Albumintocreatinineratio(ACR):30300mg/g. glomerulopathy
Associatedwithincreasedriskofprogressivekidneydiseaseandcardiovascularevents. Antiglomerularbasement
membrane(antiGBM)disease
A3(severelyincreasedalbuminuria) (Goodpasturesyndrome)
Albuminexcretionrate:>300mg/24hours. Tubulointerstitialdisease
Albumintocreatinineratio(ACR):>300mg/g. Acutetubularinjury
Largeramountsofproteinuriaareassociatedwithworserenalsurvival.Thesepatientsshouldbe Interstitialnephritis
referredtoanephrologist.
Fanconisyndrome
Nephroticrangeproteinuria
Cystickidneydisease
Urinetotalprotein:3.5g/day.
Hypercalciuria
Thepresenceofnephroticrangeproteinuriawithedema,hypoalbuminemia(<3.0g/dL),and
hyperlipidemiaisdefinedasnephroticsyndrome. Dentdisease
Glomerularproteinuria Aristolochicacidnephropathy
Urinetotalprotein:120g/day. Lightchaincastnephropathy
Passageofproteinfromglomerularcapillaryblood(mainlyalbumin)intotheurine. Urologic
Tubularproteinuria Urinarytractobstruction
Urinetotalprotein:<2g/day. Metabolic
Passageoflowmolecularweightproteins(e.g.,retinolbindingprotein,alpha2microglobulin,beta2 Metabolicsyndrome
microglobulin)intotheurine.
Diabeticnephropathy
Overflowproteinuria
Fabrydisease
Urinetotalprotein:upto20g/day.
Vascular
Overproductionofsmallproteins(e.g.,myoglobin,lightchains)leadstoincreasedglomerularfiltration
andappearanceintheurine. Hypertension
Hemolyticuremicsyndrome
Effectofalbuminuriaonprognosisofchronickidneydisease (HUS)
Thromboticthrombocytopenic
Albuminuriaisanindependentriskfactorfortheprogressionofchronickidneydisease.Severelyincreased purpura(TTP)
levelsofalbuminuriainthesettingofnormalGFRmayimpartagreaterriskforprogressivechronickidney
diseasethanmildlyreducedGFRwithnormoalbuminuria. Sclerodermarenalcrisis

Mediumandsmallvessel
vasculitis
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vasculitis
Renalveinthrombosis
Toxic
Heavymetalpoisoning
Rhabdomyolysis
(myoglobinuria)
Glomerular
Idiopathicnodular
glomerulosclerosis
Proliferativeglomerulonephritis
withmonoclonalIgGdeposits
Inflammatory/rheumatic
Polymyositis

PrognosisofCKDbyGFRandalbuminuriacategory:CKD,chronickidneydiseaseGFR,glomerularfiltrationrateKDIGO,KidneyDiseaseImprovingGlobalOutcomes
ReprintedbypermissionfromMacmillanPublishersLtd:KidneyInternationalSupplements(vol3,issue1,January2013),copyright2013

InpatientswithadvancedCKD,proteinuriaisthestrongestpredictoroftimetoendstagerenaldisease. [21]

Epidemiology
Proteinuriaiscommon,andprevalenceincreaseswithkidneydiseaseprogression.Thereisevidencethatbothmoderatelyandseverelyincreased
albuminuriaaremorecommoninblackpeoplethaninwhitepeople.AstheGFRdeclinesfrom>90mL/minute/1.73m^2to1559mL/minute/1.73m^2,the
prevalenceofmoderatelyincreasedalbuminuria(ACR<300mg/g)increasesfrom6.0%to23.2%,andtheprevalenceofseverelyincreasedalbuminuria
(ACR>300mg/g)increasesfrom0.6%to8.6%. [22]

Detection:qualitativetesting
Inlaboratories,proteinuriahastraditionallybeenroutinelydetectedthroughtheuseofmultireagenturinarydipsticktesting.
Thepresenceofurinaryalbuminisdetectedbyacolorimetricreactionwiththedipstickimpregnatedreagent.
Dipsticktestinghaslimitedsensitivityfornonalbuminprotein,andisthereforeoftenfalselynegativeinthepresenceofpredominatelytubularor
overflowproteinuria.
Thesensitivityoftheurinarydipstickforalbuminrangesfrom83%to98%withaspecificityof59%to86%. [23] [24] Thisreactiondependsonthe
concentrationofalbumin,sothetestingoflargevolume,diluteurineunderestimatesthedegreeofalbuminuria.Similarly,testinghighlyconcentrated
urinemayoverestimatethedegreeofalbuminuria.
MarkedlyalkalinepH(>8.0)andadministrationofiodinatedradiocontrastagentscanalsoproducefalsepositiveresults.
Whilequalitativedipsticktestingisrapid,easytoperform,andcommonplace,thefalsepositiveandnegativerateslimittheutility.

Dipstickproteinuriaranges
CreatedbyBMJEvidenceCentreusingauthorcontent

Inthepast,sulfosalicylicacid(SSA)wasaddedtourinespecimenstoprecipitateallprotein,forthedetectionofnonalbuminproteins.Theresultant
turbidityisgradedonascalefrom0to4+.AlthoughSSAtestingisstillused,semiquantitativeandquantitativetestingmethodshavelargelyreplacedit.

Detection:semiquantitativetesting

Newerdipstickshavebeenmarketedthatcanreportalbumintocreatinineratiosinthemicroalbuminrange,aswellastotalproteintocreatinineratios.
Standardizingtheproteinmeasurementtothequantityofcreatinineintheurinehelpsavoiderrorsintroducedbydiluteorconcentratedurinesamples.
Measuringtotalproteinalsoallowsdetectionoftubularandoverflowproteinuria.Thereportedsensitivityofthesesemiquantitativedipsticksis80%to
97%withaspecificityof33%to80%. [25]

Detection:quantitativetesting

Quantitativetestingofalbuminusingurinealbuminconcentrationoralbumintocreatinineratioissensitiveandspecificfordetectingalbuminuria. [26]
[27]

Measuringurinealbuminconcentrationwithoutmeasuringurinecreatinineconcentrationislessexpensive,andhasdemonstratedsimilarsensitivity
andspecificityasalbumintocreatinineratioforscreeningpurposesindiabetics. [27]
Twentyfourhoururinecollectionshavetraditionallybeenused,althoughthesecollectionsarepronetooverandundercollection.Moreover,24hour
urinecollectionsarecumbersomeforpatients.Reportingthetotal24hoururineproteinstandardizedtothe24hoururinecreatinine(gprotein/g
creatinine)helpsadjustforvariationsinthedurationofcollection.
Inwomen,anadequatecollectiontypicallyhas15to20mgofcreatinineperkgofbodyweight,andinmen,20to25mg/kg.

Alternatively,theexpectedgramsofexcretedcreatininecanbeestimatedby140minusagemultipliedbyweight/5000[(140age)xweight/5000],
whereweightisinkilograms.Thisresultismultipliedby0.85inwomen. [28]
Morecommonly,aurineproteintocreatinineratiooralbumintocreatinineratioonaspoturinesampleisusedtoapproximatethe24hoururine
proteinexcretionand24hoururinealbuminexcretion,respectively.
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proteinexcretionand24hoururinealbuminexcretion,respectively.
Albumintocreatinineratioismoresensitivethanproteintocreatinineratioindetectinglowlevelsofproteinuria. [29]
Afirstmorningsamplemostcloselyestimates24hourproteinexcretion,althougharandomsampleisacceptableifafirstmorningvoidisunavailable.
[3] [28] [30]

Becauseofdiurnalvariation,itisbesttocollectspoturinesamplesatthesametimeeachdayifbeingusedtofollowuppatientslongterm.Additionally,
thecorrelationofthespotsamplewith24hourexcretionislessrobustwithnephroticrangeproteinuria.Thespotratiomayalsobelessaccuratein
pregnantwomenwith>300mgofproteinuria. [31] [32]
Peoplewithbodysurfaceareasof1.73m^2excreteroughly1gofcreatinine.Assuch,aproteintocreatinineratioof1gprotein/gcreatinineinan
averagesizedpersonapproximates1gofproteinuriain24hours.Itisimportanttorecognizethataratioof2.5gprotein/gcreatinineinamuscular
personwhoexcretes2gofcreatininein24hoursmayactuallyrepresentnephroticrangeproteinuriaof5g/day.Similarly,anolder,frailwomanmay
excrete<1gofcreatinineperday,andinthissetting,thespotratiowouldoverestimateherproteinuria.

ReferencedArticles

1 ViswanathanG,UpadhyayA.Assessmentofproteinuria.AdvChronicKidneyDis.201118:243248.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/21782130

2 MontasBermdezR,GrciaGarcaS,PrezSurribasD,etal.Consensusdocument.Recommendationsonassessingproteinuria
duringthediagnosisandfollowupofchronickidneydisease.Nefrologia.201131:331345.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/21780317

3 NationalKidneyFoundation.KDOQIclinicalpracticeguidelinesforchronickidneydisease:evaluation,classification,andstratification.
AmJKidneyDis.200239(suppl1):S1S266.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/11904577
[FullText]
http://www.kidney.org/Professionals/Kdoqi/guidelines_ckd/toc.htm

4 LeveyAS,deJongPE,CoreshJ,etal.Thedefinition,classification,andprognosisofchronickidneydisease:aKDIGOControversies
Conferencereport.KidneyInt.201180:1728.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/21150873

5 ChronicKidneyDiseasePrognosisConsortiumMatsushitaK,vanderVeldeM,AstorBC,etal.Associationofestimatedglomerular
filtrationrateandalbuminuriawithallcauseandcardiovascularmortalityingeneralpopulationcohorts:acollaborativemetaanalysis.
Lancet.2010375:20732081.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/20483451

6 AstorBC,MatsushitaK,GansevoortRT,etal.Lowerestimatedglomerularfiltrationrateandhigheralbuminuriaareassociatedwith
mortalityandendstagerenaldisease.Acollaborativemetaanalysisofkidneydiseasepopulationcohorts.KidneyInt.201179:1331
1340.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/21289598

7 vanderVeldeM,MatsushitaK,CoreshJ,etal.Lowerestimatedglomerularfiltrationrateandhigheralbuminuriaareassociatedwith
allcauseandcardiovascularmortality.Acollaborativemetaanalysisofhighriskpopulationcohorts.KidneyInt.201179:13411352.
[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/21307840

8 GansevoortRT,MatsushitaK,vanderVeldeM,etal.LowerestimatedGFRandhigheralbuminuriaareassociatedwithadverse
kidneyoutcomes.Acollaborativemetaanalysisofgeneralandhighriskpopulationcohorts.KidneyInt.201180:93104.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/21289597

9 BritishMedicalJournal.LoweGFRandhighalbuminuriapredictendstagekidneydiseaseanddeathatallages.BMJ.
2012345:e7478.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/23135200

10 HanSS,AhnSY,RyuJ,etal.Proteinuriaandhematuriaareassociatedwithacutekidneyinjuryandmortalityincriticallyillpatients:a
retrospectiveobservationalstudy.BMCNephrol.201415:93.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/24942179
[FullText]
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072664/

11 LinLY,JenqCC,LiuCS,etal.Proteinuriacanpredictshorttermprognosisincriticallyillcirrhoticpatients.JClinGastroenterol.
201448:377382.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/24440941

12 BorregoJ,MazuecosA,GentilMA,etal.Proteinuriaasapredictivefactorintheevolutionofkidneytransplantation.TransplantProc.
201345:36273629.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/24314978

13 LewisEJ,HunsickerLG,BainRP,etal.Theeffectofangiotensinconvertingenzymeinhibitionondiabeticnephropathy.NEnglJMed.
1993329:14561462.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/8413456
[FullText]
http://www.nejm.org/doi/full/10.1056/NEJM199311113292004#t=article

14 TheGISENGroup.Randomisedplacebocontrolledtrialofeffectoframiprilondeclineinglomerularfiltrationrateandriskofterminal
renalfailureinproteinuric,nondiabeticnephropathy.Lancet.1997349:18571863.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/9217756

15 BrennerBM,CooperME,deZeeuwD,etal.Effectsoflosartanonrenalandcardiovascularoutcomesinpatientswithtype2diabetes
andnephropathy.NEnglJMed.2001345:861869.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/11565518
[FullText]
http://www.nejm.org/doi/full/10.1056/NEJMoa011161#t=article

16
LewisEJ,HunsickerLG,ClarkeWR,etal.Renoprotectiveeffectoftheangiotensinreceptorantagonistirbesartaninpatientswith
nephropathyduetotype2diabetes.NEnglJMed.2001345:851860.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/11565517
[FullText]
http://www.nejm.org/doi/full/10.1056/NEJMoa011303#t=article

17 ParvingHH,LehnertH,BrchnerMortensenJ,etalIrbesartaninPatientswithType2DiabetesandMicroalbuminuriaStudyGroup.
https://online.epocrates.com/dx/indexprint?entire=false&iid=875&sid=11&activeTab=9 3/4
3/4/2017 EvaluationofproteinuriaOverviewEpocratesOnline
17 ParvingHH,LehnertH,BrchnerMortensenJ,etalIrbesartaninPatientswithType2DiabetesandMicroalbuminuriaStudyGroup.
Theeffectofirbesartanonthedevelopmentofdiabeticnephropathyinpatientswithtype2diabetes.NEnglJMed.2001345:870878.
[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/11565519
[FullText]
http://www.nejm.org/doi/full/10.1056/NEJMoa011489#t=article

18 WrightJTJr,BakrisG,GreeneT,etal.Effectofbloodpressureloweringandantihypertensivedrugclassonprogressionof
hypertensivekidneydisease:resultsfromtheAASKtrial.JAMA.2002288:24212431.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/12435255
[FullText]
http://jama.amaassn.org/cgi/content/full/288/19/2421

19 InkerLA,LeveyAS,PandyaK,etal.Earlychangeinproteinuriaasasurrogateendpointforkidneydiseaseprogression:anindividual
patientmetaanalysis.AmJKidneyDis.201464:7485.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/24787763

20 KidneyDisease:ImprovingGlobalOutcomes.KDIGO2012clinicalpracticeguidelinefortheevaluationandmanagementofchronic
kidneydisease.January2013.http://www.kdigo.org(lastaccessed28June2016).[FullText]
http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf

21 GramsME,LiL,GreeneTH,etal.EstimatingtimetoESRDusingkidneyfailureriskequations:resultsfromtheAfricanAmerican
StudyofKidneyDiseaseandHypertension(AASK).AmJKidneyDis.201565:394402.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/25441435

22 AstorBC,HallanSI,MillerER3rd,etal.Glomerularfiltrationrate,albuminuria,andriskofcardiovascularandallcausemortalityinthe
USpopulation.AmJEpidemiol.2008167:12261234.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/18385206
[FullText]
http://aje.oxfordjournals.org/cgi/content/full/167/10/1226

23 SiednerMJ,GelberAC,RovinBH,etal.Diagnosticaccuracystudyofurinedipstickinrelationto24hourmeasurementasascreening
toolforproteinuriainlupusnephritis.JRheumatol.200835:8490.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/18085740

24 WhiteSL,YuR,CraigJC,etal.Diagnosticaccuracyofurinedipsticksfordetectionofalbuminuriainthegeneralcommunity.AmJ
KidneyDis.201158:1928.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/21411199

25 ComperWD,OsickaTM.Detectionofurinaryalbumin.AdvChronicKidneyDis.200512:170176.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/15822052

26 McTaggartMP,NewallRG,HirstJA,etal.Diagnosticaccuracyofpointofcaretestsfordetectingalbuminuria:asystematicreviewand
metaanalysis.AnnInternMed.2014160:550557.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/24733196

27 WuHY,PengYS,ChiangCK,etal.Diagnosticperformanceofrandomurinesamplesusingalbuminconcentrationvsratioofalbumin
tocreatinineformicroalbuminuriascreeninginpatientswithdiabetesmellitus:asystematicreviewandmetaanalysis.JAMAIntern
Med.2014174:11081115.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/24798807

28 GinsbergJM,ChangBS,MatareseRA,etal.Useofsinglevoidedurinesamplestoestimatequantitativeproteinuria.NEnglJMed.
1983309:15431546.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/6656849

29 NationalInstituteforHealthandCareExcellence.Chronickidneydiseaseinadults:assessmentandmanagement.January2015.
https://www.nice.org.uk/(lastaccessed28June2016).[FullText]
https://www.nice.org.uk/guidance/cg182/

30 JohnsonDW,JonesGR,MathewTH,etal.Chronickidneydiseaseandmeasurementofalbuminuriaorproteinuria:aposition
statement.MedJAust.2012197:224225.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/22900872
[FullText]
https://www.mja.com.au/journal/2012/197/4/chronickidneydiseaseandmeasurementalbuminuriaorproteinuriaposition

31 PapannaR,MannLK,KouidesRW,etal.Protein/creatinineratioinpreeclampsia:asystematicreview.ObstetGynecol.2008112:135
144.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/18591319

32 CtAM,BrownMA,LamE,etal.Diagnosticaccuracyofurinaryspotprotein:creatinineratioforproteinuriainhypertensivepregnant
women:systematicreview.BMJ.2008336:10031006.[Abstract]
http://www.ncbi.nlm.nih.gov/pubmed/18403498
[FullText]
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364863

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