Urine appreciation 101
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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.

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Urine appreciation 101

Urine Appreciation 101

Jason M. Eberhardt, DVM, MS, DACVIM


Why urine

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

    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 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

    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


    Urine appreciation 101

    Do you want urine with that???


    Appearance

    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

    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

    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

    Site of origin…

    • Urinary tract origin

      • Kidneys, ureters, bladder, urethra

    • Genital tract contamination

      • Prostate, prepuce, vagina


    It s not blood

    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

    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

    Specific Gravity

    • Remember dipsticks are unreliable

    • Accurate readings between 60-100°

    • “Normal” USG

      • No such thing…

      • Dehydration

        • Dog >1.030

        • Feline >1.035


    Isothenuria

    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

    Hypothenuria

    • <1.007

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

    • Persistent hypotheuria

      • Atypical/early renal failure (typically 1.006-1.007)

      • Cushing’s dz*

      • DI

      • Psychogenic


    Pu pd

    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 pd1

    PU/PD

    • Primary polydipsia

    • Diabetes insipidus

    • Resistance to ADH

    • Osmotic diuresis

    • Medullary washout

    • Misc.


    Approaching pu pd

    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

    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

    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

    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


    Urine appreciation 101

    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

    Proteinuria

    • Diagnostic marker

      • CKD

      • Systemic disease

    • Potential for progression

    • Semi-quantitative screening methods

      • Dipstick

      • Sulfosalicylic acid turbidimetric test (SSA)


    Dipsticks and proteinuria

    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

    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

    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

    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

    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

    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

    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

    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

    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

      • Urine culture

      • Infectious dz testing as appropriate

      • Blood pressure

      • Abdominal imaging

      • Endocrine testing as appropriate

      • Chest radiographs


    Concurrent disease

    Concurrent disease

    • Common to find concurrent medical conditions

      • 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

    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

    Therapy Considerations

    • 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

    ACE Inhibitors

    • It is important to start low and gradually increase with monitoring

      • Blood pressure

      • Renal Values

      • Electrolytes

      • Degree of proteinuria


    Glucosuria

    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

    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

    If repeatable…

    • Presumptive proximal tubular dysfunction

    • Further evaluation

      • Repeat hx

      • Evaluate renal function

      • Urine culture

      • Abdominal ultrasound

      • Investigate for complex renal disorders


    Ketonuria

    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

    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

    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

    JUST IGNORE IT!!!


    Sediment cells

    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

    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

    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

    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

    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

    “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

    Crystalluria

    • Formation dependant on pH, temp. & USG

    • Commonly present, seldom significant

    • Crystalluria does NOT correlate well with urolithiasis**


    So now ph matters

    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

    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

    Even more…

    • Cystine

      • Associated with cystinuria

      • Always considered “abnormal”

      • English bulldogs, Newfoundlands, Dachshunds

    • Calcium oxalate (monohydrate)

      • Associated with ethylene glycol intoxication


    Other crystals

    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

    Summary

    • Put value back into the urinalysis

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


    Wise advice

    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

    Questions


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