PET CARE VETERINARY CARE CENTER 2009 W SLAUSON AVE ACCOUNT #: ATTENDING VET: ANDERSON, DVM, JOY

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1 Text KISMET EVENTOFF PET OWNER: EVENTOFF SPECIES: Feline BREED: GENDER: Female AGE: 2 Months PATIENT ID: PET CARE VETERINARY CARE CENTER 2009 W SLAUSON AVE ACCOUNT #: ATTENDING VET: ANDERSON, DVM, JOY LAB ID: L ORDER ID: DATE OF RECEIPT: 6/21/16 DATE OF RESULT: 6/21/16 IDEXX Services: Total Health Plus with T3 and Free T4 Hematology 6/21/16 (Order Received) 6/21/16 5:37 AM (Last Updated) RBC M/µL L Hematocrit % L Hemoglobin g/dl L MCV fl MCH pg MCHC g/dl % Reticulocyte 0.2 % Reticulocyte K/µL Reticulocyte Comment A reticulocyte count of greater than 50 K/uL of blood is considered evidence of bone marrow response to an increased peripheral demand. Depending on the degree of anemia, a reticulocyte count <50 K/uL may indicate an inadequate bone marrow response. Serial monitoring of the erythrogram and absolute reticulocyte count may be useful to evaluate bone marrow responsiveness over time. The following chart can be used as a guideline to determine appropriateness of regenerative response. Degree of bone marrow response (K/uL): Mild Moderate Marked >175 WBC K/µL % Neutrophil 73.3 % % Lymphocyte 18.5 % % Monocyte 7.1 % % Eosinophil 1.1 % % Basophil 0.0 % Neutrophil K/µL Lymphocyte K/µL Monocyte K/µL H Eosinophil K/µL L Basophil K/µL Generated by VetConnect PLUS June 21, :07 PM Page 1 of 4

2 KISMET EVENTOFF PET OWNER: EVENTOFF DATE OF RESULT: 6/21/16 LAB ID: L Hematology (continued) Platelet K/µL Platelet Comments PLATELETS ARE CLUMPED ON THE BLOOD FILM. PLATELET COUNT REFLECTS MINIMUM VALUE. Poikilocytosis Anisocytosis Remarks SLIGHT SLIGHT SLIDE REVIEWED MICROSCOPICALLY. NO FELINE HEMOTROPIC MYCOPLASMAS (FHM, formerly Hemobartonella) seen. IF FHM IS SUSPECTED, THE IDEXX RealPCR FOR FHM IS MORE SENSITIVE THAN BLOOD FILM REVIEW. UNIT CODE Chemistry 6/21/16 (Order Received) 6/21/16 5:37 AM (Last Updated) Glucose mg/dl BUN mg/dl Creatinine mg/dl IDEXX SDMA BUN:Creatinine Ratio a µg/dl 27.8 Phosphorus mg/dl H Calcium mg/dl Sodium mmol/l Potassium mmol/l Na:K Ratio Chloride mmol/l TCO2 (Bicarbonate) mmol/l Anion Gap mmol/l Total Protein g/dl L Albumin g/dl Globulin g/dl L Alb:Glob Ratio ALT U/L H AST U/L H Generated by VetConnect PLUS June 21, :07 PM Page 2 of 4

3 KISMET EVENTOFF PET OWNER: EVENTOFF DATE OF RESULT: 6/21/16 LAB ID: L Chemistry (continued) ALP U/L H GGT b U/L H Bilirubin - Total mg/dl H Bilirubin - Unconjugated Bilirubin - Conjugated mg/dl H mg/dl H Cholesterol mg/dl Amylase ,239 U/L Lipase c U/L L Creatine Kinase U/L H Hemolysis Index Lipemia Index d e N N a BOTH SDMA AND CREATININE ARE WITHIN THE REFERENCE INTERVAL which indicates kidney function is likely good. If SDMA and/or creatinine is at the upper end of the reference interval, early kidney disease cannot be ruled out. Evaluate a complete urinalysis to confirm there is no other evidence of kidney disease. b RESULT VERIFIED BY REPEAT ANALYSIS c RESULT VERIFIED BY REPEAT ANALYSIS d Index of N,+,++ exhibits no significant effect on chemistry values. e Index of N,+,++ exhibits no significant effect on chemistry values. Endocrinology 6/21/16 (Order Received) 6/21/16 5:37 AM (Last Updated) Total T4 a µg/dl Total T3 < ng/dl Free T4 (ng/dl) ng/dl Free T4 (pmol/l) b pmol/l a Interpretive ranges: <0.8 Subnormal Normal Generated by VetConnect PLUS June 21, :07 PM Page 3 of 4

4 KISMET EVENTOFF PET OWNER: EVENTOFF DATE OF RESULT: 6/21/16 LAB ID: L Endocrinology (continued) Grey zone in old or symptomatic cats >4.7 Consistent with hyperthyroidism Cats with subnormal T4 values are almost exclusively euthyroid sick or overtreated for their hyperthyroidism. Older cats with consistent clinical signs and T4 values in the grey zone may have early hyperthyroidism or a concurrent non-thyroidal illness. Hyperthyroidism may be confirmed in these cats by adding on a free T4 or by performing a T3 suppression test. Following treatment with methimazole, T4 values will generally fall within the lower end of the reference range ( ). b In middle-aged to older cats with clinical signs of hyperthyroidism and a total T4 in the "grey zone" or upper end of the reference interval, an increased free T4 supports the diagnosis of hyperthyroidism. A normal free T4 makes the diagnosis of hyperthyroidism unlikely, but if a strong clinical suspicion remains, repeat thyroid testing in 6 to 8 weeks or a technesium scan is indicated. Generated by VetConnect PLUS June 21, :07 PM Page 4 of 4

5 SDMA (Symmetric Dimethylarginine) Interpretive Summary Description: Symmetric dimethylarginine (SDMA) is a new kidney function test. It increases earlier than creatinine in some animals with chronic kidney disease (CKD). Unlike creatinine, SDMA is not impacted by lean body mass giving it the potential to be a more sensitive indicator of kidney function as CKD progresses and the pet loses weight. SDMA and creatinine should be interpreted together, along with a urinalysis. For additional information about SDMA, please visit µg/dl) Common Causes Normal SDMA with normal or low Creatinine o Normal kidney function is likely If SDMA and/or creatinine is at the upper limit of the reference interval, early kidney disease cannot be ruled out. Evaluate a complete urinalysis to confirm there is no other evidence of kidney disease. Normal SDMA with high Creatinine o Kidney disease is possible If SDMA is at or very near the upper limit of the reference interval, biologic and assay variability may be contributing to the rare incidence of a normal SDMA in face of high creatinine. SDMA and creatinine results will likely align with repeat testing over time. Determine if there is other evidence of kidney disease such as supportive history, abnormal kidney palpation, inappropriate urine specific gravity, proteinuria and/or abnormal imaging. o Muscular dogs with normal kidney function may have a normal SDMA and creatinine just exceeding the reference interval. Assess body condition and complete urinalysis to help determine significance of these results. o Certain breeds, including Greyhounds and Great Pyrenees, have higher creatinine concentration than other breeds and creatinine results often fall above the reference interval while their SDMA concentrations remain normal. o SDMA results may be depressed by 10-25% in dogs and 10-20% in cats if severe hemolysis is present. Increased SDMA (>14 µg/dl) Common Causes High SDMA with normal or low Creatinine o Renal Disease Early kidney disease is likely SDMA increases earlier than creatinine in early renal disease. Most animals with early kidney disease have an SDMA between 15- disease along with an increased creatinine. An increased SDMA with normal creatinine may be seen in animals with reversible kidney damage if the underlying cause is identified or resolves on its own. Examples would include pyelonephritis, acute kidney injury secondary to infectious (e.g. leptospirosis) or drug therapy (e.g. nonsteroidal antiinflammatory drugs). In poorly muscled animals, creatinine may be a poor indicator of renal function. SDMA is a more sensitive indicator of kidney function in poorly muscled animals. Infectious, inflammatory, toxic and ischemic renal diseases are most common. Generated by VetConnect PLUS: June 21, :07 PM Symmetric Dimethylarginine (SDMA) Page 1 of 4

6 o interpreted in light of other findings. o Evaluate for other evidence of kidney disease such as supportive history, abnormal kidney palpation, inappropriate urine specific gravity, proteinuria and/or abnormal imaging. High SDMA with high Creatinine o Renal Disease Kidney function is likely impaired Infectious, inflammatory, toxic and ischemic renal diseases are most common. Confirm that there is other evidence of kidney disease such as supportive history, abnormal kidney palpation, inappropriate urine specific gravity, proteinuria and/or abnormal imaging. Uncommon Causes High SDMA with high Creatinine o Renal Disease Congenital kidney disease, amyloidosis, and renal neoplasia are less common causes of renal disease. o Dehydration If dehydration results in a prerenal azotemia reflecting a reduction in glomerular filtration rate (GFR), then SDMA should also increase along with creatinine. Assess hydration status and urine specific gravity for evidence of dehydration. o Post-renal If ureteral or urethral obstruction results in a decrease in GFR, then SDMA will increase along with creatinine. Related Findings Renal disease o Increased BUN, creatinine and phosphorus SDMA can be increased prior to development of azotemia o Electrolyte abnormalities, metabolic acidosis, hypo- or hypercalcemia o Mild to moderate nonregenerative anemia o Inappropriate urine specific gravity. o Urinary casts, pyuria, hematuria, proteinuria, microalbuminuria, glucosuria, bacteriuria o Positive urine culture o Increased blood pressure o Protein losing nephropathy (glomerulonephritis or amyloidosis) Decreased albumin Increased urine protein:creatinine ratio High cholesterol in nephrotic syndrome o Positive PCR or serology for leptospirosis, Lyme disease, ehrlichiosis or other infections o Abnormal kidney imaging findings such as abnormal renal size and/or structure o History of kidney toxin exposure Additional Information Physiology SDMA is a molecule formed by post-translational methylation of the amino acid L-arginine in the nucleus of cells by protein-arginine methyltransferase enzymes. o During protein degradation these methylated arginine molecules are released. o Biologically, SDMA is considered an inert molecule. SDMA is eliminated by renal excretion, therefore blood concentrations are affected by changes in GFR making SDMA a good marker for renal disease. Generated by VetConnect PLUS: June 21, :07 PM Symmetric Dimethylarginine (SDMA) Page 2 of 4

7 SDMA is a biomarker for kidney function and has been shown to rise in proportion to creatinine and is inversely related to GFR (measured by iohexol clearance) in dogs and cats with kidney disease. SDMA increases earlier than creatinine in chronic kidney disease. o SDMA increases on average with 40% loss of kidney function versus creatinine, which does not increase until 75% of kidney function is lost. o In cats, SDMA increases on average of 17 months before creatinine. o In dogs, SDMA increases on average of 9.5 months before creatinine. SDMA is specific for kidney function. It is not impacted by various diseases including liver disease, Cushing s disease and heart disease, unless there is concurrent kidney disease SDMA is not impacted by lean body mass. Reductions in lean body mass occur with aging and chronic disease can lower creatinine concentrations, but SDMA increases as kidney function declines with no correlation to lean body mass. Week to week variability of iohexol clearance, serum creatinine and SDMA are similar in dogs with stable renal disease in puppies, kittens and Greyhounds with normal kidney function. Diagnostic Methodology No information is currently available on how to interpret SDMA in species other than dogs and cats. SDMA is measured at IDEXX Reference Laboratories using a high throughput immunoassay. SDMA can be performed on serum or lithium heparin plasma. SDMA is stable for 4 days at room temperature and 14 days refrigerated. It is also stable for years in specimens that remain frozen and do not undergo freeze thaw cycles. Lipemia, hemolysis and icterus do not affect SDMA results. Severe hemolysis may slightly decrease SDMA (10-25% in dogs; 10-20% in cats). Rarely in specimens with severe hemolysis and lipemia, SDMA cannot be measured. Reference Braff J, Aguiar J, Yerramilli M, et al. Analysis of Serum Symmetric Dimethylarginine Concentration in Patient Samples Identified Through Retrospective Trending of Serum Creatinine. [ACVIM Abstract U-43] J Vet Intern Med. 2014; 28(3): Braff J, Obare E, Yerramilli M, et al. Relationship Between Serum Symmetric Dimethylarginine Concentration and Glomerular Filtration Rate in Cats. J Vet Intern Med. 2014, Vol 28: Hall JA, Yerramilli M, Obare E, et al. Comparison of Serum Concentrations of Symmetric Dimethylarginine and Creatinine as Kidney function Biomarkers in Cats with Chronic Kidney Disease. J Vet Intern Med. 2014, Vol 28: Hall JA, Yerramilli M, Obare E, et al. Comparison of Serum Concentrations of Symmetric Dimethylarginine and Creatinine as Kidney Biomarkers In Healthy Geriatric Cats Fed Reduced Protein Foods Enriched with Fish Oil, L- carnitine, and Medium Chain Triglycerides. Vet J. 2014, Vol 202: Hall JA, Yerramilli M, Obare E, et al. Relationship between lean body mass and serum renal biomarkers in healthy dogs. J Vet Intern Med. 2015;29(3): Jepson, RE, Syme HM, Vallance C, et al. Plasma Asymmetric Dimethylarginine, Symmetric Dimethylarginine, L- Arginine, and Nitrite/Nitrate Concentrations in Cats with Chronic Kidney Disease and Hypertension. J Vet Intern Med Vol 22: Jewell DE, Fritsch D, Yerramilli M, et al. Feeding Reduced Protein and Phosphorus Food to Dogs with Naturally Occurring Renal Disease Reduces Serum Concentrations of Creatinine and Symmetric Dimethylarginine (SDMA). [ACVIM Abstract NU-27]. J Vet Intern Med. 2014; 28(3): p Jewell DE, Yerramilli M, Obare E, et al. Foods with Controlled Protein and Phosphorus and Enhanced with Antioxidents Vitamin E and C Reduce Circulating Urea and Symmetrical Di-Methyl Arginine, and Increase Isosine in Dogs. [ACVIM Abstract NM-10]. J Vet Intern Med. 2013; 27(3): p744. Jewell DE, Yerramilli M, Obare E, et al. Increasing Dietary Protein Concentration from 15% to 30% in a One Year Study Increases Glomerular Filtration Rate and Reduces Creatinine and Symmetrical Di-Methyl Arginine. [ACVIM Abstract NM-9]. J Vet Intern Med. 2013; 27(3): p744. Nabity MB, Lees GE, Boggess M, et al. Correlation of Symmetric Dimethylarginine with Glomerular Filtration Rate in Dogs with Chronic Progressive Renal Disease. [ACVIM Abstract NU-11]. J Vet Intern Med. 2013; 27(3): 733. Nabity MB, Lees GE, Boggess M, et al. Week to Week Variability of Iohexol Clearance, Serum Creatinine, and Symmetric Dimethylarginine in Dogs with Stable Chronic Renal Disease. [ACVIM Abstract NU-14]. J Vet Intern Med. 2013; 27(3): 734. Generated by VetConnect PLUS: June 21, :07 PM Symmetric Dimethylarginine (SDMA) Page 3 of 4

8 Nabity MB, Lees GE, Boggess M, et al. Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease. J Vet Intern Med. 2015; 29(4): Padmanabahan M, Obare E, Yerramilli M. LCMS Method Development and Validation for a Potential Chronic Kidney Disease Marker Symmetrical Dimethyl Arginine. [ACVIM Abstract NU-21]. J Vet Intern Med. 2013; 27(3): 736. Patch D, Obare E, Xie H, et al. High Throughput Immunoassay That Correlates to Gold Standard Liquid Chromatography-Mass Spectometry (LC-MS) Assay for the Chronic Kidney Disease (CKD) Marker Symmetric Dimethylarginine (SDMA). J Vet Intern Med. 2015; pg. 95. Early View, Article first published online: 27 MAY DOI: /jvim Rentko V, Nabity M, Yerramilli M, et al. Determination of Serum Symmetric Dimethylarginine Reference Limit in Clinically Healthy Dogs. [ACVIM Abstract P-7]. J Vet Intern Med. 2013; 27(3): 750. Yerramilli M, Yerramilli M, Obare E, et al. Symmetric Dimethylarginine (SDMA) Increases Earlier than Serum Creatinine in Dogs with Chronic Kidney Disease (CKD). [ACVIM Abstract NU-42]. J Vet Intern Med. 2014; 28(3): Last Updated 11/18/2015 Generated by VetConnect PLUS: June 21, :07 PM Symmetric Dimethylarginine (SDMA) Page 4 of 4