Urine Protein Creatinine Ratio IDEXX Today s Agenda

Urine Protein Creatinine Ratio IDEXX

Today’s Agenda l Product Overview l Action Selling l What is it? l Sell yourself l How do I run it? l Sell IDEXX l Who should I run it on? l Sell UPC l When should I run it? l l 2 How do I interpret the results? Who is my competition? © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Urine P: C Ratio 3 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Product Overview l Sample Preparation Kit l 2 fixed volume disposable pipettes l l l 4 Packaged in pairs, 6 ratios per box 2 Vet. Test runs (1 UPRO, 1 UCRE) Total instrument run time 12 minutes © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18 l Sterile water l Urine P: C Ratio Pipette tips Instruction insert Quality Control l l UCRE – Vet. Trol® control fluid UPRO – UPRO control fluid

What are UPRO and UCRE? l UPRO and UCRE are two new Vet. Test® Chemistry Slides that will soon be available for use on all Vet. Test® Chemistry Analyzers. l l l 5 UPRO is the abbreviation for Urine Protein. UCRE is the abbreviation for Urine Creatinine. These new Vet. Test® Slides are specifically calibrated for urine samples © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

How is a Urine P: C Ratio calculated? l l 6 A Urine P: C Ratio is calculated by dividing Urine Protein by Urine Creatinine (UPRO/UCRE). The new Vet. Test® Chemistry Slides will be packaged in pairs (1 UPRO next to 1 UCRE) for convenience of running and calculating a Urine P: C Ratio. © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

How do I run a Urine P: C Ratio on the Vet. Test®? 1. 2. 3. 4. 7 Perform the urine protein (UPRO) test. While the urine protein test is running, prepare the sample mixture for the urine creatinine test. Perform the urine creatinine (UCRE) test. Calculate the urine protein: creatinine ratio. © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Perform the urine protein (UPRO) test Instructions taken from the: A. Perform the urine protein (UPRO) test. 1. Select “New Sample” from the Vet. Test main menu, select the patient species (e. g. , canine or feline) and enter the patient identification information. 2. Insert the urine protein slide into the Vet. Test slide loading tray with the bar code facing up and the notch on the left. Gently push the loading tray in as far as it will go, and then pull it back out. 3. When the analyzer is ready, remove the pipettor from the analyzer’s holder and place a new plastic tip on its end. 4. Push the tip on firmly and put the pipettor back in its holder. 5. When the Vet. Test display tells you to, lower the pipettor into the urine sample. 6. Press and release the button on top of the pipettor. Keep the pipette tip in the sample until the analyzer beeps twice. Remove the pipettor from the sample. 7. When the analyzer beeps three times, carefully wipe the end of the pipette tip with a twisting motion using a clean, disposable lint-free tissue. 8. Immediately place the pipettor back in its holder. A single beep indicates the start of the sample analysis. Analysis takes approximately six minutes. 8 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

While the urine protein test is running, prepare the sample mixture for the urine creatinine test. Instructions taken from the: B. Prepare the urine creatinine mixture. 1. Attach a clean tip to the yellow Mini. Pet, draw 10 µL of urine from the sample and place it into a sample cup. 2. Attach a clean tip to the white Mini. Pet, draw 200 µL of UCRE mix from the bottle and place it into a sample cup. 3. Use the white Mini. Pet to draw the mixture up and down in the sample cup 4– 5 times to mix it 9 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Perform the urine creatinine (UCRE) test Instructions taken from the: C. Perform the urine creatinine test. 1. Select “Current Sample” from the Vet. Test main menu, and select “No” when asked if you want to perform a dilution. 2. Insert the urine creatinine slide into the Vet. Test slide loading tray with the bar code facing up and the notch on the left. Gently push the loading tray in as far as it will go, and then pull it back out. 3. When the Vet. Test display tells you to, lower the pipettor into the sample mixture. 4. Press and release the button on top of the pipettor. Keep the pipette tip in the sample until the analyzer beeps twice. Remove the pipettor from the sample. 5. When the analyzer beeps three times, carefully wipe the end of the pipette tip with a twisting motion using a clean, disposable lint-free tissue. 6. Immediately place the pipettor back in its holder. A single beep indicates the start of the sample analysis. Analysis takes approximately six minutes. 10 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Calculate the urine protein: creatinine ratio. Instructions taken from the: D. Calculate the urine protein: creatinine ratio. Divide the UPRO result by the UCRE result and compare the value to the suggested reference range that appears on the Vet. Test printout and above in the IDEXX Vet. Test Ranges section. 11 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

When will UPC be available on Vet. Test® Chemistry Analyzers? l l l 12 UPC is on schedule to be introduced in December 2004. At that time, all Vet. Test® customers will receive a software upgrade that notifies them that UPC is now available on the Vet. Test. The software will automatically upgrade their Vet. Test with the calibration information necessary to run UPRO and UCRE for dogs and cats. © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

What are Urine P: C Ratios used for? l l 13 A Urine P: C Ratio allows the veterinarian to assess urinary protein loss. This gives the practitioner the ability to screen for early renal disease, better evaluate underlying disease, monitor disease progression, and measure response to treatment. © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

What does a Urine P: C Ratio measure? l l l 14 A Urine P: C Ratio is a quantitative measure of protein loss by the kidneys. Small amounts of protein can normally be found in urine, however significant amounts of protein in urine can be a sign of renal disease, or other underlying non-renal disease. A Urine P: C Ratio is used to determine if the amount of protein in the urine (proteinuria) is significant, and if further patient monitoring, investigation, or intervention is necessary. © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Why Perform a Urine P: C Ratio? l Proteinuria is a growing concern in veterinary medicine l l l UPC is the best available test for: l l l screening for proteinuria, and measuring persistence & magnitude guiding clinical decisions, and monitoring response to therapy 2004 ACVIM Consensus Statement highly supportive of UPC l 15 increasing evidence of its association with bad patient outcomes persistent proteinuria with an inactive sediment indicates chronic kidney disease vets should give more attention to detection, evaluation, monitoring, and treatment of proteinuria © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Why is screening for Proteinuria with a UP: C ratio important for the practitioner? l l 16 The ability to calculate Urine P: C Ratios quickly and conveniently in-house allows for detection of renal disease months, and even years, before traditional tests would indicate renal damage. This allows both the practitioner and pet owner significantly more time to provide patient care, thereby extending both the duration and quality of patient lives. © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Why is screening for Proteinuria with a UPC ratio important for the pet owner? l l 17 Renal disease is a progressive, morbid condition that requires significant time and effort on the part of the pet owner. The treatments and change in diet and lifestyle require a serious commitment. Early detection of renal disease decreases the morbidity and improves the prognosis. Sequential UP: C ratios allow the pet owner to quantify the effects of their labor and treatment, and better care for their pet. © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Which patients should be screened using the Urine P: C Ratio? l Urine P: C Ratios should be performed in the clinical evaluation of dogs and cats that: show any sign of renal disease l present sick (“ain’t doing right”) l are senior patients, where there is a heightened concern about potential renal disease l l l 18 Should be considered as a component of routine “wellness” evaluations of apparently healthy at-risk dogs and cats. For animals in which proteinuria is documented or suspected, determinations of UP: C ratios should be performed to guide clinical decision-making and to monitor ongoing trends. © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Breed Disposition to Various Renal Diseases l l l l l 19 Airedale Terriers (RD) Alaskan Malamutes (RD) Basenjis (Fanconi-like syndrome) Beagles (unilateral agenesis, dysplasia, & polycystic kidneys) Bedlington Terriers (RD) Boxers (RD) Bulldogs (RD) Bull Terriers (glomerulopathy) Cairn Terriers (polycystic kidneys) Chinese Shar-Pei (amyloidosis) Chows (RD) Cocker Spaniels (glomerulopathy) Collies (glomerulopathy) Doberman Pinschers (unilateral agenesis and glomerulopathy) Golden Retrievers (RD) Great Danes (RD) Great Pyrenees (RD) Irish Wolfhounds (RD) Keeshonds (RD) © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18 l l l l l King Charles Spaniels (RD) Lhasa Apso (RD) Miniature Poodles (polycystic kidneys) Miniature Schnauzers (RD and Fanconilike syndrome) Newfoundlands (glomerulopathy) Norwegian Elkhounds (tubulointerstitial nephropathy and Fanconi-like syndrome Old English Sheepdogs (RD) Pekingese (unilateral agenesis and RD) Samoyeds (glomerulopathy) Shetland Sheepdogs (unilateral agenesis, medullary cystic disease and Fanconi-like syndrome) Shih Tzus (RD) Soft-Coated Wheaten Terriers (RD) Standard Poodles (RD) Swedish Foxhounds (RD) Welsh Corgis (telangiectasia) Yorkshire Terriers (RD)

Interpreting Urine P: C Ratio l l 20 UP: C (urine protein/urine creatinine) ratios as an indicator of proteinuria are interpreted differently in canine and feline populations, as well as in azotemic and nonazotemic patients. Azotemia is an increase in blood urea nitrogen and creatinine levels. Remember, by the time a patient is azotemic, it has already lost over 75% of its renal function and is in renal failure. UP: C Ratio = urine protein divided by urine creatinine (UPRO / UCRE) © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

21 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Urine P: C Ratio Evaluation: l 1 st: localize the protein to the kidney l l Protein may come from sources l BEFORE the kidney l IN the kidney l AFTER the kidney 2 nd: determine persistence Chronic or Acute l Cause of an underlying disease or situation? l l 22 3 rd: evaluate severity © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Localization: 1 st priority in UPC analysis l Causes of proteinuria can be pre-renal, renal or postrenal l 23 Pre-renal: evaluate for Bence Jones proteins, myoglobin, hemoglobin Renal: determine level of azotemia l Inactive sediment Post-renal: evaluate urine sediment for signs of inflammation and infection, stones and tumors l Active sediment © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Persistence: 2 nd priority in UPC analysis l l l Determine persistence of proteinuria by repeating UP: C Ratios This should be performed on 3 or more occasions The tests should be repeated at least 2 weeks apart from one another Treatment can start immediately! 24 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Evaluation: 3 rd priority of Urine P: C Ratio Results l Depends on level of azotemia l Depends on species Canine l Feline l 25 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Evaluation: Non-azotemic animals with persistent proteinuria l NON-AZOTEMIC & PERSISTENT PROTEINURIA WITH INACTIVE URINE SEDIMENT (DOGS & CATS): UPC < 0. 5 – no significant proteinuria l UPC ≥ 0. 5 < 1. 0 – requires further monitoring l UPC ≥ 1. 0 < 2. 0 – proteinuria l UPC ≥ 2. 0 – excessive proteinuria l 26 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Evaluation: Azotemic dogs with persistent proteinuria l AZOTEMIC DOGS & PERSISTENT PROTEINURIA WITH INACTIVE URINE SEDIMENT (DOGS): UPC < 0. 5 – no significant proteinuria l UPC ≥ 0. 5 – excessive proteinuria l 27 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Evaluation: Azotemic cats with persistent proteinuria l AZOTEMIC CATS & PERSISTENT PROTEINURIA WITH INACTIVE URINE SEDIMENT (CATS): UPC < 0. 4 – no significant proteinuria l UPC ≥ 0. 4 – excessive proteinuria l 28 © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

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Implications of Urine P: C Results: l Proteinuric animals (of renal origin) might benefit from antiproteinuric therapy Dietary protein restriction l N 3 fatty acid supplementation l Phosphorus restriction / phosphorus binders l SQ fluid therapy l ACE (angiotensin-converting enzyme inhibitor treatment) inhibitor therapy l l 30 These animals should be monitored frequently to evaluate response to treatment and disease progression © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18

Take Home Message l The Vet. Test® Urine P: C Ratio is the only in-house, fully quantitative test that allows the veterinarian to: l l better evaluate underlying non-renal disease l monitor disease progression l 31 screen for early renal disease measure response to treatment © 2002 IDEXX LABORATORIES, INC. | Proprietary and Confidential | 16 -Mar-18