Urine Appreciation Urine Appreciation 101101

Jason M. Eberhardt, DVM, Jason M. Eberhardt, DVM, MS, DACVIMMS, DACVIM

Why Urine?Why Urine?

• ““Urine…the wine of the body”Urine…the wine of the body”– Dr. WilkeDr. Wilke

• ““God made urine gold for a reason”God made urine gold for a reason”– Dr. BargesDr. Barges

• ““Don’t ever give me another set of Don’t ever give me another set of blood work without a urinalysis”blood work without a urinalysis”

– Dr. DeClue to an internDr. DeClue to an intern

The Routine UrinalysisThe Routine Urinalysis

• Should be performed…“routinely” Should be performed…“routinely”

• It’s part of a sentenceIt’s part of a sentence– CBC, Chemistry, UA.CBC, Chemistry, UA.

• Provides invaluable data of overall Provides invaluable data of overall healthhealth– Regardless of clinical status of patientRegardless of clinical status of patient

Sample CollectionSample Collection

• Sample Method MattersSample Method Matters– Cystocentesis is typically preferableCystocentesis is typically preferable– Hematuria?Hematuria?

• Try to evaluate fresh samplesTry to evaluate fresh samples– Can affect interpretationCan affect interpretation– Warm refrigerated samples prior to Warm refrigerated samples prior to

evaluationevaluation

Aspects of a UA Aspects of a UA

• Physical PropertiesPhysical Properties– AppearanceAppearance– Specific gravitySpecific gravity

• Chemical PropertiesChemical Properties– pH, Protein, Glucose, Ketones, Blood, pH, Protein, Glucose, Ketones, Blood,

Bilirubin, Leukocyte Esterase RxnBilirubin, Leukocyte Esterase Rxn

• Urine Sediment ExaminationUrine Sediment Examination• Specific testsSpecific tests

Do you want urine

with that???

Appearance Appearance

• Why is urine yellow?Why is urine yellow?

• Depth of color is RELATED to volume Depth of color is RELATED to volume and concentrationand concentration– YELLOW URINE DOES NOT MEAN YELLOW URINE DOES NOT MEAN

CONCENTRATED URINE!CONCENTRATED URINE!

• What about abnormal pigmenturia???What about abnormal pigmenturia???

Red to reddish-brownRed to reddish-brown

• RBC’sRBC’s

• HemoglobinHemoglobin

• MyoglobinMyoglobin– To distinguish – centrifugationTo distinguish – centrifugation

•Hematuria will clearHematuria will clear

•Hemoglobinuria/myoglobinuria will notHemoglobinuria/myoglobinuria will not

• Key in determining further diagnostic Key in determining further diagnostic planplan

Causes of hematuriaCauses of hematuria• TraumaTrauma

– Traumatic collectionTraumatic collection -Iatrogenic increase without gross -Iatrogenic increase without gross change is common, Renal Bx, Blunt traumachange is common, Renal Bx, Blunt trauma

• UrolithiasisUrolithiasis• NeoplasiaNeoplasia• Inflammatory DzInflammatory Dz

– UTI, FLUTD/FUSUTI, FLUTD/FUS, Drug induced (ie cyclophosphamide induced , Drug induced (ie cyclophosphamide induced cystitis)cystitis)

• Parasites (Parasites (Dioctophyma renal, Capillaria plicaDioctophyma renal, Capillaria plica))• Coagulopathy - Warfarin toxicity, DIC, ThrombocytopeniaCoagulopathy - Warfarin toxicity, DIC, Thrombocytopenia• Renal infarctionRenal infarction• Renal pelvic hematomaRenal pelvic hematoma• Vascular malformation – Vascular malformation –

– Renal telangiectasia (Welsh Corgi’s), Idiopathic renal Renal telangiectasia (Welsh Corgi’s), Idiopathic renal hematuriahematuria

• EstrusEstrus• Inflammation, neoplasia, trauma to genital tractInflammation, neoplasia, trauma to genital tract

Site of origin…Site of origin…

• Urinary tract origin Urinary tract origin – Kidneys, ureters, bladder, urethraKidneys, ureters, bladder, urethra

• Genital tract contaminationGenital tract contamination– Prostate, prepuce, vaginaProstate, prepuce, vagina

It’s not blood…It’s not blood…

• HemoglobinuriaHemoglobinuria– Common Common AbAbnormal pigmentnormal pigment– Serum is typically pinkSerum is typically pink– Usually indicates hemolysisUsually indicates hemolysis

• MyoglobinuriaMyoglobinuria– Serum is typically ClearSerum is typically Clear– Usually indicates severe rhadomyolysisUsually indicates severe rhadomyolysis

Other changesOther changes

• Yellow brown/greenYellow brown/green– Bilirubin – Pre-hepatic, Hepatic, Post-hepaticBilirubin – Pre-hepatic, Hepatic, Post-hepatic

• Cloudy-whiteCloudy-white– Increased cellular elements, crystals, mucusIncreased cellular elements, crystals, mucus

• Brown-blackBrown-black– Post Oxyglobin administrationPost Oxyglobin administration

• Smell…Smell…– Ammonia produced by urease-producing Ammonia produced by urease-producing

bacteriabacteria

Specific GravitySpecific Gravity

• Remember dipsticks are unreliableRemember dipsticks are unreliable

• Accurate readings between 60-100Accurate readings between 60-100°°

• ““Normal” USGNormal” USG– No such thing…No such thing…– DehydrationDehydration

•Dog >1.030Dog >1.030

•Feline >1.035Feline >1.035

IsothenuriaIsothenuria

• 1.008-1.0121.008-1.012– Neither concentrated nor dilutedNeither concentrated nor diluted

• Owner may or may not report PU/PDOwner may or may not report PU/PD– Recheck morning sample if no clinical Recheck morning sample if no clinical

signssigns

• Accurate history!Accurate history!

HypothenuriaHypothenuria

• <1.007<1.007

• Indicates renal ability to dilute glomerular Indicates renal ability to dilute glomerular filtrate (renal failure is not present?)filtrate (renal failure is not present?)

• Persistent hypotheuriaPersistent hypotheuria– Atypical/early renal failure (typically 1.006-Atypical/early renal failure (typically 1.006-

1.007)1.007)– Cushing’s dz*Cushing’s dz*– DIDI– PsychogenicPsychogenic

PU/PDPU/PD

• Go back to basicsGo back to basics

• History, History, HistoryHistory, History, History

• Is the patient drinking too much Is the patient drinking too much causing them to urinate more or…causing them to urinate more or…

• Is the patient urinating more so they Is the patient urinating more so they have to drink more…have to drink more…

PU/PDPU/PD

• Primary polydipsiaPrimary polydipsia

• Diabetes insipidusDiabetes insipidus

• Resistance to ADH Resistance to ADH

• Osmotic diuresisOsmotic diuresis

• Medullary washoutMedullary washout

• Misc.Misc.

Approaching PU/PDApproaching PU/PD

• Common things are common…Common things are common…– Dogs: CKD, DM, Cushing’sDogs: CKD, DM, Cushing’s– Cats: CKD, DM, HyperthyroidismCats: CKD, DM, Hyperthyroidism

• CDI, Primary NDI, Psychogenic are rare!CDI, Primary NDI, Psychogenic are rare!• Initial plans should be simple and safeInitial plans should be simple and safe

– Water deprivation does not meet this criteriaWater deprivation does not meet this criteria

• Use Use specificspecific test results to r/o test results to r/o specificspecific dz dz– Urine culture for pyelonephritis Urine culture for pyelonephritis

• Look it up and mark them off!Look it up and mark them off!

Urine pHUrine pH

• Normal is between 5.0-7.5Normal is between 5.0-7.5– Some resources list up to 8.5Some resources list up to 8.5

• Varies with diet and acid-base Varies with diet and acid-base balancebalance

• Dipsticks have moderate to poor Dipsticks have moderate to poor correlation with pH meters correlation with pH meters

pH ContinuedpH Continued

• Refrigeration for up to 24 hours does Refrigeration for up to 24 hours does not clinically impact pHnot clinically impact pH– However, leaving at room temperature However, leaving at room temperature

leads to COleads to CO2 2 contamination contamination

• IS NOT RELIABLE INDEX OF BLOOD IS NOT RELIABLE INDEX OF BLOOD pHpH– Hypochloremic metabolic alkalosis can Hypochloremic metabolic alkalosis can

have aciduriahave aciduria

Causes of urine pH Causes of urine pH alterationsalterations

• Low pHLow pH– Meat ingestion, acidosis, hypochloremic Meat ingestion, acidosis, hypochloremic

metabolic alkalosis, diarrhea, starvation, pyrexia, metabolic alkalosis, diarrhea, starvation, pyrexia, urine acidifiers, proximal renal tubular acidosisurine acidifiers, proximal renal tubular acidosis

• High pHHigh pH– Postprandial alkaline tide, ingestion of alkali Postprandial alkaline tide, ingestion of alkali

(bicarb or citrate), alkalosis, UTI w/urease-(bicarb or citrate), alkalosis, UTI w/urease-producing bacteria (usually producing bacteria (usually StaphStaph or or ProteusProteus spp.), high vegetable/cereal diets, distal renal spp.), high vegetable/cereal diets, distal renal tubular acidosistubular acidosis

So…So…

• It can be a challenge to determine the It can be a challenge to determine the exact significance of urine pH (especially exact significance of urine pH (especially in a single sample and/or not comparing to in a single sample and/or not comparing to blood pH)blood pH)

• Persistent alkalosis Persistent alkalosis couldcould prompt further prompt further diagnostics (ie urine culture)diagnostics (ie urine culture)

• pH can affect other urinalysis findingspH can affect other urinalysis findings– Glucose (Low pH)Glucose (Low pH)– Protein (high pH)Protein (high pH)– Crystal formationCrystal formation

ProteinuriaProteinuria

• Diagnostic markerDiagnostic marker– CKDCKD– Systemic diseaseSystemic disease

• Potential for progressionPotential for progression

• Semi-quantitative screening methodsSemi-quantitative screening methods– DipstickDipstick– Sulfosalicylic acid turbidimetric test Sulfosalicylic acid turbidimetric test

(SSA)(SSA)

Dipsticks and ProteinuriaDipsticks and Proteinuria

• Primarily measures albumin Primarily measures albumin • False positivesFalse positives

– Alkaline urineAlkaline urine– Active sediment (“Post-renal”)Active sediment (“Post-renal”)– Left in contact with stick too longLeft in contact with stick too long

• False negativesFalse negatives– Bence-Jones proteins, low specific Bence-Jones proteins, low specific

gravity, proteinuria <30 mg/dlgravity, proteinuria <30 mg/dl

SSA TestSSA Test

• Urine + 5% SSAUrine + 5% SSA

• Grade turbidity on scale 0-4Grade turbidity on scale 0-4– SUBJECTIVESUBJECTIVE

• Detects albumin, Bence-Jones, Detects albumin, Bence-Jones, globulinsglobulins

• FP: Drugs (including Penicillins and FP: Drugs (including Penicillins and Cephalosporins)Cephalosporins)

• Can detect >5 mg/dlCan detect >5 mg/dl

Microalbuminuria testMicroalbuminuria test

• Detects >1 mg/mlDetects >1 mg/ml

• If dipstick and SSA are positiveIf dipstick and SSA are positive– What’s the point???What’s the point???

1) Equivocal/conflicting results?1) Equivocal/conflicting results?

2) More sensitive test is desired?2) More sensitive test is desired?

3) Familial risk3) Familial risk

USG and ProteinuriaUSG and Proteinuria

• Most resources cite that if USG Most resources cite that if USG >1.035 then 1+ protein is “normal”>1.035 then 1+ protein is “normal”

• At what USG is trace to 1+ protein At what USG is trace to 1+ protein NOT normalNOT normal– ??????

Urine protein:creatinine Urine protein:creatinine ratioratio

• What is normal???What is normal???– <0.5 Dogs; <0.3 Cats<0.5 Dogs; <0.3 Cats– 0.5-1.0 Mild0.5-1.0 Mild– >1.0 – 2.0 Moderate>1.0 – 2.0 Moderate– >2.0 Severe (typically glomerular dz)>2.0 Severe (typically glomerular dz)

LocalizationLocalization

• Physiologic/FunctionalPhysiologic/Functional– Technically a “renal” cause of proteinuriaTechnically a “renal” cause of proteinuria– Strenuous exercise, seizures, Strenuous exercise, seizures, feverfever, extreme , extreme

environmental exposuresenvironmental exposures– Transient, low grade & does not require specific Transient, low grade & does not require specific

txtx

• PathologicalPathological– Extra UrinaryExtra Urinary

• Pre-renal vs. Genital systemPre-renal vs. Genital system

– UrinaryUrinary• Renal vs. Post-renalRenal vs. Post-renal

Extra Urinary CausesExtra Urinary Causes

• Genital tract inflammationGenital tract inflammation– Comparison of cysto. vs. free-catch Comparison of cysto. vs. free-catch

samplessamples

• DysproteinemiasDysproteinemias– Bence-Jones proteinsBence-Jones proteins

•Dipstick negative, positive SSADipstick negative, positive SSA

– Hemoglobin/myoglobinHemoglobin/myoglobin

Urinary CausesUrinary Causes

• Rule out “post” renal causes firstRule out “post” renal causes first– Infection, neoplasia, urolithiasisInfection, neoplasia, urolithiasis

• Primary RenalPrimary Renal– GlomerularGlomerular

•Most common cause of persistent, high-Most common cause of persistent, high-magnitude magnitude

– Tubular-interstitialTubular-interstitial•May also have other findings of tubular May also have other findings of tubular

disorderdisorder

Practical evaluationPractical evaluation

• Evaluate History and PE findingsEvaluate History and PE findings• Go back and look at blood workGo back and look at blood work

– Proteins, renal values, cholesterol, electrolytesProteins, renal values, cholesterol, electrolytes

• Evaluate other UA findingsEvaluate other UA findings• Further diagnosticsFurther diagnostics

– Urine cultureUrine culture– Infectious dz testing as appropriateInfectious dz testing as appropriate– Blood pressureBlood pressure– Abdominal imagingAbdominal imaging– Endocrine testing as appropriateEndocrine testing as appropriate– Chest radiographsChest radiographs

Concurrent diseaseConcurrent disease

• Common to find concurrent medical Common to find concurrent medical conditionsconditions– NeoplasiaNeoplasia– Infection (dental dz, heartworm, etc.)Infection (dental dz, heartworm, etc.)– Immune mediated dzImmune mediated dz– Systemic hypertensionSystemic hypertension– Viral (cats)Viral (cats)

• 43% of patients with severe proteinuria do 43% of patients with severe proteinuria do not have an identifiable concurrent disease not have an identifiable concurrent disease

(Cook and Cowgill, 1996).(Cook and Cowgill, 1996).

When to treat?When to treat?

• Recommendations continue to Recommendations continue to change…change…

• Depends on concurrent disease(s)Depends on concurrent disease(s)

• Azotemia vs. Non-azotemic patientsAzotemia vs. Non-azotemic patients– Azotemia: Consider even if mild?Azotemia: Consider even if mild?

•ACVIM ConsensusACVIM Consensus– >0.5 dogs; >0.3 Cats>0.5 dogs; >0.3 Cats

– Non-azotemic: If persistently moderate-Non-azotemic: If persistently moderate-severesevere

Therapy ConsiderationsTherapy Considerations

• Discontinue renal toxic medicationsDiscontinue renal toxic medications• Tx underlying conditionsTx underlying conditions• Reduced (not necessarily low) protein dietReduced (not necessarily low) protein diet• ACE inhibitorsACE inhibitors• Low dose aspirin supplementationLow dose aspirin supplementation

– Only if hypoalbuminemic?Only if hypoalbuminemic?• Fatty acid supplementationFatty acid supplementation• Always investigate/address hypertensionAlways investigate/address hypertension• Immunosuppression???????Immunosuppression???????

ACE InhibitorsACE Inhibitors

• It is important to start low and It is important to start low and gradually increase with monitoringgradually increase with monitoring– Blood pressureBlood pressure– Renal ValuesRenal Values– ElectrolytesElectrolytes– Degree of proteinuriaDegree of proteinuria

GlucosuriaGlucosuria

• Glucose reabsorption occurs in the Glucose reabsorption occurs in the proximal tubuleproximal tubule

• Typically occurs when renal Typically occurs when renal threshold is exceededthreshold is exceeded– >180 mg/dl Dogs>180 mg/dl Dogs– >300 mg/dl Cats>300 mg/dl Cats

They’re not diabetic…They’re not diabetic…

• Recheck dipstick 1stRecheck dipstick 1st• Abnormal proximal Abnormal proximal

tubular functiontubular function• Simple vs. ComplexSimple vs. Complex

– ToxinToxin•Aminoglycoside toxicityAminoglycoside toxicity

– Fanconi’s diseaseFanconi’s disease– Primary renal glucosuriaPrimary renal glucosuria

If repeatable…If repeatable…

• Presumptive proximal tubular Presumptive proximal tubular dysfunctiondysfunction

• Further evaluationFurther evaluation– Repeat hxRepeat hx– Evaluate renal functionEvaluate renal function– Urine cultureUrine culture– Abdominal ultrasoundAbdominal ultrasound– Investigate for complex renal disordersInvestigate for complex renal disorders

KetonuriaKetonuria

• Ketones produced by lipolysisKetones produced by lipolysis– Occurs earlier in young animalsOccurs earlier in young animals

• Dipsticks react to acetoacetate and Dipsticks react to acetoacetate and acetoneacetone

• PositivePositive– DMDM, Drugs, prolonged starvation, low carb , Drugs, prolonged starvation, low carb

diets (Atkin’s diet), persistent fever, diets (Atkin’s diet), persistent fever, persistent hypoglycemia, glycogen storage persistent hypoglycemia, glycogen storage dzdz

BilirubinBilirubin

• Dogs have lower renal thresholdDogs have lower renal threshold– Male dogs can have 1+ in concentrated urineMale dogs can have 1+ in concentrated urine– Positive is nearly always important in catsPositive is nearly always important in cats

• All the same causes as hyperbilirubinemiaAll the same causes as hyperbilirubinemia– Will see prior to serum increasesWill see prior to serum increases

• Can help differentiate lab error on Can help differentiate lab error on chemistrychemistry

Misc. dipstick resultsMisc. dipstick results

• Leukocyte esterase reactionLeukocyte esterase reaction– Low sensitivity in dogs Low sensitivity in dogs

•High number of false negativesHigh number of false negatives

– Low specificity in cats Low specificity in cats •High number of false positivesHigh number of false positives

• Rely on high quality urine sediment Rely on high quality urine sediment examexam

• Urobilingen and Nitrites – WWHD???Urobilingen and Nitrites – WWHD???

JUST IGNORE IT!!!JUST IGNORE IT!!!

Sediment - CellsSediment - Cells

• RBCs, WBCs, BacteriaRBCs, WBCs, Bacteria

• Epithelial CellsEpithelial Cells– Both squamous and transitional cells can be Both squamous and transitional cells can be

found in sedimentfound in sediment– Typically of little diagnostic significanceTypically of little diagnostic significance

• Neoplastic cellsNeoplastic cells– Fresh samplesFresh samples– New methylene blue or Wright’s-Giemsa stainsNew methylene blue or Wright’s-Giemsa stains– Difficult to differentiate from “reactive” changesDifficult to differentiate from “reactive” changes

Bladder Tumor Antigen TestBladder Tumor Antigen Test

• Detects a glycoprotein antigen Detects a glycoprotein antigen complex associated with bladder complex associated with bladder cancer (humans)cancer (humans)– Sensitivity 90%; Specificity 78%Sensitivity 90%; Specificity 78%

• False positivesFalse positives– Proteinuria, glucosuria, pyuria, hematuriaProteinuria, glucosuria, pyuria, hematuria– Specificity only 41% in urinary tract dz Specificity only 41% in urinary tract dz

other then TCCother then TCC– PPV 3% (NPV 100%)PPV 3% (NPV 100%)

CylindruriaCylindruria

• Supports presence of renal diseaseSupports presence of renal disease– Type can give indication to disease Type can give indication to disease

processprocess

• Composed of aggregated proteins or Composed of aggregated proteins or cellscells– Form in ascending limb of Henle and Form in ascending limb of Henle and

distal tubulesdistal tubules– Best evaluated on fresh samplesBest evaluated on fresh samples

Hyaline CastsHyaline Casts

• Pure protein precipitates Pure protein precipitates – Mucoprotein + albuminMucoprotein + albumin

• Actually dissolve rapidly in dilute or Actually dissolve rapidly in dilute or alkaline urinealkaline urine

• Typically seen in diseases that cause Typically seen in diseases that cause proteinuriaproteinuria– Can also be seen with diuresis, correcting Can also be seen with diuresis, correcting

dehydrationdehydration– Consider further evaluation for proteinuria???Consider further evaluation for proteinuria???

Other “casts” of charactersOther “casts” of characters

• GranularGranular– Degenerating cells, proteins and other “stuff”Degenerating cells, proteins and other “stuff”– Supportive of acute tubular injurySupportive of acute tubular injury

• Toxic, IschemicToxic, Ischemic

• CellularCellular– WBCs, Epithelial, RBCsWBCs, Epithelial, RBCs– Pyelonephritis, acute tubular injuryPyelonephritis, acute tubular injury

• Waxy castsWaxy casts– ““Old” granular castsOld” granular casts

““Casting your lot”Casting your lot”

• Presence of casts are often the first Presence of casts are often the first sign of tubular injurysign of tubular injury– EVALUATE FRESH SAMPLESEVALUATE FRESH SAMPLES

• Useful in monitoring for toxicityUseful in monitoring for toxicity– AminoglycosidesAminoglycosides– AmphotericinAmphotericin– Ingestions Ingestions

CrystalluriaCrystalluria

• Formation dependant on pH, temp. & Formation dependant on pH, temp. & USGUSG

• Commonly present, seldom Commonly present, seldom significant significant

• Crystalluria does Crystalluria does NOTNOT correlate well correlate well with urolithiasis**with urolithiasis**

So now pH matters…So now pH matters…

• Acidic urineAcidic urine– Uric acid, calcium oxalate and cystineUric acid, calcium oxalate and cystine

• Alkaline Alkaline – Struvite, calcium phosphate, calcium Struvite, calcium phosphate, calcium

carbonate, amorphous phosphates, carbonate, amorphous phosphates, ammonium biurateammonium biurate

Struvite and Calcium Struvite and Calcium OxalateOxalate

• Both commonly seen in normal dogsBoth commonly seen in normal dogs

• MAY BEMAY BE associated with calculi and associated with calculi and infectioninfection

• Should Should notnot automatically prompt automatically prompt therapy or diet changetherapy or diet change

Even more…Even more…

• Cystine Cystine – Associated with cystinuriaAssociated with cystinuria– Always considered “abnormal”Always considered “abnormal”– English bulldogs, Newfoundlands, English bulldogs, Newfoundlands,

DachshundsDachshunds

• Calcium oxalate (monohydrate)Calcium oxalate (monohydrate)– Associated with ethylene glycol Associated with ethylene glycol

intoxicationintoxication

Other crystalsOther crystals

• BilirubinBilirubin– May be normal vs. high bilirubinMay be normal vs. high bilirubin

• Ammonium urate and Uric acidAmmonium urate and Uric acid– ““Normal” in Dalmations and English Normal” in Dalmations and English

BulldogsBulldogs– Portosystemic shunts (congenital or Portosystemic shunts (congenital or

acquired)acquired)– Hepatic insufficiencyHepatic insufficiency

SummarySummary

• Put value back into the urinalysisPut value back into the urinalysis

• Can gain useful insight of the overall Can gain useful insight of the overall picture of each patientpicture of each patient

Wise advice…Wise advice…

• "I do not recommend drinking urine…"I do not recommend drinking urine…but if you drink water straight from but if you drink water straight from the river, you have a greater chance the river, you have a greater chance of getting an infection than you do if of getting an infection than you do if you drink urine." you drink urine."

- Howard Dean to 8 year old- Howard Dean to 8 year old

QuestionsQuestions