Woodley Equipment Company Ltd. E.R.D.-HealthScreen® Urine Tests Paul Lymer, B.Sc. European Sales...

Woodley Equipment Company Ltd.

E.R.D.-HealthScreen® Urine Tests

Paul Lymer, B.Sc.

European Sales Manager

Woodley Equipment Company Ltd.

E.R.D.-HealthScreen® Urine Tests

What do you know about kidneys?

E.R.D.-HealthScreen® Test

What is its purpose?

Used to detect albumin in the urine

Urinary System

Kidney

What are the functions of the kidneys?

• Filtering the blood • Removing excess water and

waste from the blood (urine)• Sending urine to the bladder• Releasing hormones into the

blood

Regulate water and soluble substances by:

How does a normal kidney handle albumin?

4 mg/dL albumin goes in

2-3 mg/dL albumin normally

leaks through glomerulus and isreabsorbed by the

proximal tubule <<1 mg/dL albumin

comes outRusso et al 2002 AJKD 39:899

D’Amico and Bazzi 2003 Kidn Internt’l 63:809

The Glomerulus at work

The kidneys filter a dog’s or cat’s entire blood volume every 30 minutes.

Systemic Disease & Albuminuria

• Antigen-Antibody Complexes• Vasculitis• Hypertension

The most common protein associated with kidney damage is albumin.

1º Causes of 2º renal damage

• Inflammatory diseases

• Infectious diseases

• Metabolic diseases

• Neoplasia

• Hypertension

• Drugs

1º Causes of 2º renal damage

• Inflammatory diseases– Dental disease– Pyoderma– IBD– Immune mediated diseases

• Infectious diseases– Heartworm disease– Tick-borne diseases– Viral diseases

• Metabolic diseases– Diabetes mellitus– Hyperadrenocorticism– Hyperthyroidism

• Hypertension• Neoplasia• Drugs

Introduction to

E.R.D.-HealthScreen Urine

Test Technology

Microalbuminuria testing in Dogs and Cats

• Semiquantitative in-clinic test (E.R.D.-HealthScreenTM Urine Tests)

• Species-specific monoclonal antibodies to albumin• Detects as little as 1 mg/dl of albumin in the urine• No maximum limit of detection• Microalbuminuria: 1-30 mg/dl

3 Easy Steps

1.070

1.060

1.050

1.040

1.030

1.020

Sample (1 mL)

Dilute Sample Read ResultsInsert Device,Wait 3 minutes

Interpretation of Results

Bottom Band NegativeDarker

Bands Equal Low Positive

Top band Medium PositiveSlightly Darker

Top band High PositiveMuch Darker

Top Band Very Very High Dark, Bottom PositiveBand Absent

What Do You See? Results

(~ 1 mg/dL)

Clinical Signs

Subclinical Disease

“Veterinarians should give more attention to the detection, evaluation, monitoring, and treatment of dogs and cats with proteinuria.”

Dr. George Lees in his introduction toSmall Animal Consensus Statement Draft on “Assessment and Management of Proteinuria in Dogs and Cats” ACVIM 2004

The Kidney as a “Sentinel”

Proteinuria/Albuminuria Detection

• Marker of systemic disease– Inflammatory/Infectious– Metabolic– Neoplasia

CanineMicroalbuminuriaPrevalence Study

Prevalence of Microalbuminuria in Dogs Owned by Veterinary Staff (n = 3041)

Relationship between age and percentage of dogs testing positive on the E.R.D.-HealthScreen Urine Test, n = 3041.

Prevalence of Microalbuminuria in Selected Age Groups of Dogs Owned

by Veterinary Staff (n = 3041)

Feline Microalbuminuria Prevalence Study

• No appropriate cat models of renal disease• Feline MA Study modeled after Canine Staff Testing Study• Any cat, any age, any collection method, any health status

Cat’s Name Age Sex (circle one) M CM F SF Breed

Collection Method (circle one) Expression Cystocentesis Litter Box

Presentation (circle one) Well-pet exam Neuter Dental Medical Visit

Medical History/Medications

Prevalence of Microalbuminuria in Cats (n = 1243)

0

10

20

30

40

50

60

70

80

90

100

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 >19Age, Years

Perc

ent P

ositi

ve

Relationship between age and percentage of cats testing positive on the E.R.D.-HealthScreen Urine Test, n = 1243

Prevalence of Microalbuminuria in Selected Age Groups of Cats (n =

1243)Age Group # of Positives Total # of Cats Percent Positive Increase in Prevalence

< 3 40 361 11.1%3 - 5 46 228 20.2% 9.1%6 - 8 41 184 22.3% 2.1%9 - 11 45 180 25.0% 2.7%

12 - 15 83 213 39.0% 14.0%> 16 50 77 64.9% 25.9%

--

Prevalence of Microalbuminuria in Selected Age Groups of Cats

Proteinuria/Albuminuria Detection

• Marker of renal disease

Primary renal causes of albuminuria

• Antiglomerular basement membrane disease• Renal inflammation• Renal neoplasia• Genetic renal disease

Genetic Renal Disease

Detection of Kidney Damage

E.R.D.-HealthScreen™ Urine Test• Identifies early renal damage• Early treatment and preventive measures can be initiated

Conventional Testing• Azotemia, isosthenuria• Late-stage kidney disease identified

100%

0%

25-33%

Early DetectionCapability

Proteinuria/Albuminuria Detection

• Marker of disease progression/prognosis

Proteinuria is associated with reduced survival times in nonazotemic cats. (Walker, ACVIM Abstract 2004)

“Proteinuria is associated with bad outcomes.” (Lees, ACVIM 2004)

Proteinuria predicts reduced survival times in cats with chronic renal failure. (Syme, ACVIM Abstract 2003)

The relative risk for uremic crises and mortality was approximately 3 times higher in dogs with UP/C ≥ 1.0 compared to dogs with UP/C ratio < 1.0.

(Polzin, ACVIM Abstract 2004)

Proteinuria/Albuminuria Detection

• Treatment efficacy

Treatment Efficacy• Humans

– Hypertension– Diabetes mellitus

• Dogs and cats– Anecdotal

• Lyme disease• Heartworm disease• Dental disease• Hypertension

– Studies ongoing

When should you test for albuminuria?

• Breeds at risk for hereditary/familial renal disease (early age)• Part of a prophylactic health maintenance program

– Dogs ≥ 6 years– Cats ≥ 8 years

• Anytime you have reason to evaluate a CBC, serum biochemistry profile, and UA

• Follow-up as indicated by previous results

E.R.D.-HealthScreen® Test Positive

All Positives• Complete urinalysis• Physical examination

Discretionary Testing

• CBC; Chemistry Panel• Blood Pressure measurement

E.R.D.-HealthScreen® Test Positive

Low/Medium Positives• Determine trend• Repeat test twice at one-to-three month interval

Proteinuria/Albuminuria is significant only if it is persistent.

It is most significant when it is increasing.

E.R.D.-HealthScreen® Test Positive

High/Very High Positives

• Run UPC to quantify amount of albuminuria

Microalbuminuria Stable or Decreasing

• Recheck patient every 6-12 months– physical examination

– urinalysis + E.R.D.-HealthScreenTM Urine Test

– serum creatinine

Recommendations for Monitoring

Microalbuminuria Increasing

• Recheck patient every 3-6 months– Physical examination

– Urinalysis + E.R.D.-HealthScreenTM Urine Test

– Serum creatinine

– Blood pressure

Recommendations for Monitoring

Other methods of detecting albuminuria

Components of a Complete Urinalysis

• Physical Characteristics• color, appearance, specific gravity,

and odor• Biochemical Analysis

• pH, glucose, ketones, bilirubin, occult blood, and protein

• Microscopic Analysis• RBCs, WBCs, Casts, Crystals, and

Bacteria• ± Culture

Urine dipstick

Sensitivity SpecificityDog 54% 68%Cat 60% 31%

If you exclude hematuria, pyuria and bacteruria:Dog Specificity = 84%Cat Specificity = 55%

Grauer ACVIM 2004

Screening tests for proteinuria:Sulfosalicylic acid test

• Advantages– Inexpensive– Easy to use– ↑ Sensitivity

• Disadvantages– More labor/time compared with the

dipstick– Subjective grading– ↓ Specificity for albumin

Urine Protein/Creatinine Ratio

• Quantitative test for proteinuria• Not as sensitive as SSA or MA• Best for tracking progression of proteinuric patients• Available at reference labs & on IDEXX VetTest® Chemistry

Analyzer• Ratio > 1.0 Abnormal• Ratio 0.5-1.0 Borderline (Abnormal?)• Ratio < 0.5 Normal

• Individual patient variation

Urine protein-creatinine ratio

Specific Gravity vs. Urine Creatininen=593

1.000

1.010

1.020

1.030

1.040

1.050

1.060

1.070

0.0 200.0 400.0 600.0 800.0

Urine Creatinine (mg/dl)

Sp

ec

ific

Gra

vit

y

R2 = 0.6942

UPC calculations

• Urine specific gravity____1.030____• UPC = Urine protein/Urine creatinine• Urine protein ____65___________• Urine creatinine 1. 29.2 2. 228

• UPC 1. 2.2 2. 0.3

Urine Protein Detection Methods• Dipstick

– Many false positives

• SSA– More accurate than dipstick– Subjective interpretation

• Urine protein/creatinine ratio– Interpatient variation in urine creatinine at same specific gravity– Quantitative

• Microalbuminuria– E.R.D.-Healthscreen® Urine Test– Most sensitive and specific of all methods

Lev

el o

f R

esp

onse

Magnitude of Proteinuria

Monitor

Investigate

Intervene

Response to Persistent Renal Albuminuria

MonitorMonitor

Investigate

ACVIM 2004

Optimizing Proteinuria Testing• Dipstick positives

–Sediment exam• Dipstick negative or Dipstick positive with negative

sediment–E.R.D.-HealthScreen® Tests

• Once patient is confirmed to have persistent proteinuria–Monitor trend with UPC (quantitative)

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