Urine Appreciation 101
Jason M. Eberhardt, DVM, MS,
DACVIM
Why Urine?
• “Urine…the wine of the body”
– Dr. Wilke
• “God made urine gold for a reason”
– Dr. Barges
• “Don’t ever give me another set of blood
work without a urinalysis”
– Dr. DeClue to an intern
The Routine Urinalysis
• Should be performed…“routinely”
• It’s part of a sentence
– CBC, Chemistry, UA.
• Provides invaluable data of overall health
– Regardless of clinical status of patient
Sample Collection
• Sample Method Matters
– Cystocentesis is typically preferable
– Hematuria?
• Try to evaluate fresh samples
– Can affect interpretation
– Warm refrigerated samples prior to evaluation
Aspects of a UA
• Physical Properties
– Appearance
– Specific gravity
• Chemical Properties
– pH, Protein, Glucose, Ketones, Blood,
Bilirubin, Leukocyte Esterase Rxn
• Urine Sediment Examination
• Specific tests
Do you want
urine with
that???
Appearance
• Why is urine yellow?
• Depth of color is RELATED to volume and
concentration
– YELLOW URINE DOES NOT MEAN
CONCENTRATED URINE!
• What about abnormal pigmenturia???
Red to reddish-brown
• RBC’s
• Hemoglobin
• Myoglobin
– To distinguish – centrifugation
• Hematuria will clear
• Hemoglobinuria/myoglobinuria will not
• Key in determining further diagnostic plan
Causes of hematuria
• Trauma
– Traumatic collection -Iatrogenic increase without gross change is
common, Renal Bx, Blunt trauma
• Urolithiasis
• Neoplasia
• Inflammatory Dz
•
•
•
•
•
– UTI, FLUTD/FUS, Drug induced (ie cyclophosphamide induced
cystitis)
Parasites (Dioctophyma renal, Capillaria plica)
Coagulopathy - Warfarin toxicity, DIC, Thrombocytopenia
Renal infarction
Renal pelvic hematoma
Vascular malformation –
– Renal telangiectasia (Welsh Corgi’s), Idiopathic renal hematuria
• Estrus
• Inflammation, neoplasia, trauma to genital tract
Site of origin…
• Urinary tract origin
– Kidneys, ureters, bladder, urethra
• Genital tract contamination
– Prostate, prepuce, vagina
It’s not blood…
• Hemoglobinuria
– Common Abnormal pigment
– Serum is typically pink
– Usually indicates hemolysis
• Myoglobinuria
– Serum is typically Clear
– Usually indicates severe rhadomyolysis
Other changes
• Yellow brown/green
– Bilirubin – Pre-hepatic, Hepatic, Post-hepatic
• Cloudy-white
– Increased cellular elements, crystals, mucus
• Brown-black
– Post Oxyglobin administration
• Smell…
– Ammonia produced by urease-producing bacteria
Specific Gravity
• Remember dipsticks are unreliable
• Accurate readings between 60-100°
• “Normal” USG
– No such thing…
– Dehydration
• Dog >1.030
• Feline >1.035
Isothenuria
• 1.008-1.012
– Neither concentrated nor diluted
• Owner may or may not report PU/PD
– Recheck morning sample if no clinical signs
• Accurate history!
Hypothenuria
• <1.007
• Indicates renal ability to dilute glomerular filtrate
•
(renal failure is not present?)
Persistent hypotheuria
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–
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Atypical/early renal failure (typically 1.006-1.007)
Cushing’s dz*
DI
Psychogenic
PU/PD
• Go back to basics
• History, History, History
• Is the patient drinking too much causing
them to urinate more or…
• Is the patient urinating more so they have
to drink more…
PU/PD
• Primary polydipsia
• Diabetes insipidus
• Resistance to ADH
• Osmotic diuresis
• Medullary washout
• Misc.
Approaching PU/PD
• Common things are common…
– Dogs: CKD, DM, Cushing’s
– Cats: CKD, DM, Hyperthyroidism
• CDI, Primary NDI, Psychogenic are rare!
• Initial plans should be simple and safe
– Water deprivation does not meet this criteria
• Use specific test results to r/o specific dz
– Urine culture for pyelonephritis
• Look it up and mark them off!
Urine pH
• Normal is between 5.0-7.5
– Some resources list up to 8.5
• Varies with diet and acid-base balance
• Dipsticks have moderate to poor
correlation with pH meters
pH Continued
• Refrigeration for up to 24 hours does not
clinically impact pH
– However, leaving at room temperature leads
to CO2 contamination
• IS NOT RELIABLE INDEX OF BLOOD pH
– Hypochloremic metabolic alkalosis can have
aciduria
Causes of urine pH alterations
• Low pH
– Meat ingestion, acidosis, hypochloremic metabolic
alkalosis, diarrhea, starvation, pyrexia, urine
acidifiers, proximal renal tubular acidosis
• High pH
– Postprandial alkaline tide, ingestion of alkali (bicarb or
citrate), alkalosis, UTI w/urease-producing bacteria
(usually Staph or Proteus spp.), high vegetable/cereal
diets, distal renal tubular acidosis
So…
• It can be a challenge to determine the exact
•
•
significance of urine pH (especially in a single
sample and/or not comparing to blood pH)
Persistent alkalosis could prompt further
diagnostics (ie urine culture)
pH can affect other urinalysis findings
– Glucose (Low pH)
– Protein (high pH)
– Crystal formation
Proteinuria
• Diagnostic marker
– CKD
– Systemic disease
• Potential for progression
• Semi-quantitative screening methods
– Dipstick
– Sulfosalicylic acid turbidimetric test (SSA)
Dipsticks and Proteinuria
• Primarily measures albumin
• False positives
– Alkaline urine
– Active sediment (“Post-renal”)
– Left in contact with stick too long
• False negatives
– Bence-Jones proteins, low specific gravity,
proteinuria <30 mg/dl
SSA Test
• Urine + 5% SSA
• Grade turbidity on scale 0-4
– SUBJECTIVE
• Detects albumin, Bence-Jones, globulins
• FP: Drugs (including Penicillins and
Cephalosporins)
• Can detect >5 mg/dl
Microalbuminuria test
• Detects >1 mg/ml
• If dipstick and SSA are positive
– What’s the point???
1) Equivocal/conflicting results?
2) More sensitive test is desired?
3) Familial risk
USG and Proteinuria
• Most resources cite that if USG >1.035
then 1+ protein is “normal”
• At what USG is trace to 1+ protein NOT
normal
– ???
Urine protein:creatinine ratio
• What is normal???
– <0.5 Dogs; <0.3 Cats
– 0.5-1.0 Mild
– >1.0 – 2.0 Moderate
– >2.0 Severe (typically glomerular dz)
Localization
• Physiologic/Functional
– Technically a “renal” cause of proteinuria
– Strenuous exercise, seizures, fever, extreme
environmental exposures
– Transient, low grade & does not require specific tx
• Pathological
– Extra Urinary
• Pre-renal vs. Genital system
– Urinary
• Renal vs. Post-renal
Extra Urinary Causes
• Genital tract inflammation
– Comparison of cysto. vs. free-catch samples
• Dysproteinemias
– Bence-Jones proteins
• Dipstick negative, positive SSA
– Hemoglobin/myoglobin
Urinary Causes
• Rule out “post” renal causes first
– Infection, neoplasia, urolithiasis
• Primary Renal
– Glomerular
• Most common cause of persistent, high-magnitude
– Tubular-interstitial
• May also have other findings of tubular disorder
Practical evaluation
• Evaluate History and PE findings
• Go back and look at blood work
– Proteins, renal values, cholesterol, electrolytes
• Evaluate other UA findings
• Further diagnostics
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Urine culture
Infectious dz testing as appropriate
Blood pressure
Abdominal imaging
Endocrine testing as appropriate
Chest radiographs
Concurrent disease
• Common to find concurrent medical conditions
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–
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Neoplasia
Infection (dental dz, heartworm, etc.)
Immune mediated dz
Systemic hypertension
Viral (cats)
• 43% of patients with severe proteinuria do not
have an identifiable concurrent disease
(Cook and Cowgill, 1996).
When to treat?
• Recommendations continue to change…
• Depends on concurrent disease(s)
• Azotemia vs. Non-azotemic patients
– Azotemia: Consider even if mild?
• ACVIM Consensus
– >0.5 dogs; >0.3 Cats
– Non-azotemic: If persistently moderate-severe
Therapy Considerations
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•
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Discontinue renal toxic medications
Tx underlying conditions
Reduced (not necessarily low) protein diet
ACE inhibitors
Low dose aspirin supplementation
– Only if hypoalbuminemic?
• Fatty acid supplementation
• Always investigate/address hypertension
• Immunosuppression???????
ACE Inhibitors
• It is important to start low and gradually
increase with monitoring
– Blood pressure
– Renal Values
– Electrolytes
– Degree of proteinuria
Glucosuria
• Glucose reabsorption occurs in the
proximal tubule
• Typically occurs when renal threshold is
exceeded
– >180 mg/dl Dogs
– >300 mg/dl Cats
They’re not diabetic…
• Recheck dipstick 1st
• Abnormal proximal
tubular function
• Simple vs. Complex
– Toxin
• Aminoglycoside toxicity
– Fanconi’s disease
– Primary renal glucosuria
If repeatable…
• Presumptive proximal tubular dysfunction
• Further evaluation
– Repeat hx
– Evaluate renal function
– Urine culture
– Abdominal ultrasound
– Investigate for complex renal disorders
Ketonuria
• Ketones produced by lipolysis
– Occurs earlier in young animals
• Dipsticks react to acetoacetate and
acetone
• Positive
– DM, Drugs, prolonged starvation, low carb
diets (Atkin’s diet), persistent fever, persistent
hypoglycemia, glycogen storage dz
Bilirubin
• Dogs have lower renal threshold
– Male dogs can have 1+ in concentrated urine
– Positive is nearly always important in cats
• All the same causes as hyperbilirubinemia
– Will see prior to serum increases
• Can help differentiate lab error on
chemistry
Misc. dipstick results
• Leukocyte esterase reaction
– Low sensitivity in dogs
• High number of false negatives
– Low specificity in cats
• High number of false positives
• Rely on high quality urine sediment exam
• Urobilingen and Nitrites – WWHD???
JUST IGNORE IT!!!
Sediment - Cells
• RBCs, WBCs, Bacteria
• Epithelial Cells
– Both squamous and transitional cells can be found in
sediment
– Typically of little diagnostic significance
• Neoplastic cells
– Fresh samples
– New methylene blue or Wright’s-Giemsa stains
– Difficult to differentiate from “reactive” changes
Bladder Tumor Antigen Test
• Detects a glycoprotein antigen complex
associated with bladder cancer (humans)
– Sensitivity 90%; Specificity 78%
• False positives
– Proteinuria, glucosuria, pyuria, hematuria
– Specificity only 41% in urinary tract dz other
then TCC
– PPV 3% (NPV 100%)
Cylindruria
• Supports presence of renal disease
– Type can give indication to disease process
• Composed of aggregated proteins or cells
– Form in ascending limb of Henle and distal
tubules
– Best evaluated on fresh samples
Hyaline Casts
• Pure protein precipitates
– Mucoprotein + albumin
• Actually dissolve rapidly in dilute or alkaline
•
urine
Typically seen in diseases that cause proteinuria
– Can also be seen with diuresis, correcting dehydration
– Consider further evaluation for proteinuria???
Other “casts” of characters
• Granular
– Degenerating cells, proteins and other “stuff”
– Supportive of acute tubular injury
• Toxic, Ischemic
• Cellular
– WBCs, Epithelial, RBCs
– Pyelonephritis, acute tubular injury
• Waxy casts
– “Old” granular casts
“Casting your lot”
• Presence of casts are often the first sign
of tubular injury
– EVALUATE FRESH SAMPLES
• Useful in monitoring for toxicity
– Aminoglycosides
– Amphotericin
– Ingestions
Crystalluria
• Formation dependant on pH, temp. & USG
• Commonly present, seldom significant
• Crystalluria does NOT correlate well with
urolithiasis**
So now pH matters…
• Acidic urine
– Uric acid, calcium oxalate and cystine
• Alkaline
– Struvite, calcium phosphate, calcium
carbonate, amorphous phosphates,
ammonium biurate
Struvite and Calcium Oxalate
• Both commonly seen in normal dogs
• MAY BE associated with calculi and
infection
• Should not automatically prompt therapy
or diet change
Even more…
• Cystine
– Associated with cystinuria
– Always considered “abnormal”
– English bulldogs, Newfoundlands, Dachshunds
• Calcium oxalate (monohydrate)
– Associated with ethylene glycol intoxication
Other crystals
• Bilirubin
– May be normal vs. high bilirubin
• Ammonium urate and Uric acid
– “Normal” in Dalmations and English Bulldogs
– Portosystemic shunts (congenital or acquired)
– Hepatic insufficiency
Summary
• Put value back into the urinalysis
• Can gain useful insight of the overall
picture of each patient
Wise advice…
• "I do not recommend drinking urine…but
if you drink water straight from the river,
you have a greater chance of getting an
infection than you do if you drink urine."
- Howard Dean to 8 year old
Questions