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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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3/4/2017 EvaluationofproteinuriaOverviewEpocratesOnline
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.

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