PAQUITO RAMIREZ RAMIREZ

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1 PAQUITO RAMIREZ PET OWNER: RAMIREZ SPECIES: Cnine BREED: Chihuhu GENDER: Mle AGE: 12 Yers PATIENT ID: A Byshore Veterinry Clinic 2043 NE 140th. Street ACCOUNT #: ATTENDING VET: DAVILA,MARGARITA LAB ID: ORDER ID: COLLECTION DATE: 5/17/17 DATE OF RECEIPT: 5/18/17 DATE OF RESULT: 5/18/17 IDEXX Services: Senior Profile with Hertworm -Stndrd CBC Hemtology 5/18/17 (Order Received) 5/18/17 7:58 AM (Lst Updted) RBC M/µL Hemtocrit % Hemoglobin g/dl MCV fl MCH pg MCHC g/dl % Reticulocyte 0.7 % Reticulocyte K/µL WBC K/µL % Neutrophil 56.7 % % Lymphocyte 20.5 % % Monocyte 5.6 % % Eosinophil 17.1 % % Bsophil 0.1 % Neutrophil K/µL Lymphocyte K/µL Monocyte K/µL Eosinophil K/µL Bsophil K/µL Pltelet K/µL Chemistry 5/18/17 (Order Received) 5/18/17 7:58 AM (Lst Updted) Generted by VetConnect PLUS My 19, :26 AM Pge 1 of 5

2 PAQUITO RAMIREZ PET OWNER: RAMIREZ DATE OF RESULT: 5/18/17 LAB ID: Chemistry (continued) Glucose mg/dl H µg/dl Cretinine mg/dl BUN mg/dl BUN:Cretinine Rtio 25.7 Phosphorus mg/dl Clcium mg/dl Sodium mmol/l Potssium mmol/l N:K Rtio Chloride mmol/l TCO2 (Bicrbonte) mmol/l Anion Gp mmol/l Totl Protein g/dl Albumin g/dl Globulin g/dl Alb:Glob Rtio ALT U/L AST U/L ALP U/L GGT U/L Bilirubin - Totl mg/dl Bilirubin - Unconjugted Bilirubin - Conjugted mg/dl mg/dl Cholesterol mg/dl L Amylse ,469 U/L Lipse U/L Cretine Kinse U/L H Hemolysis Index b N Lipemi Index c N Generted by VetConnect PLUS My 19, :26 AM Pge 2 of 5

3 PAQUITO RAMIREZ PET OWNER: RAMIREZ DATE OF RESULT: 5/18/17 LAB ID: Chemistry (continued) BOTH SDMA AND CREATININE ARE WITHIN THE REFERENCE INTERVAL which indictes kidney function is likely good. Evlute complete urinlysis nd confirm there is no other evidence of kidney disese. b c Index of N, 1+, 2+ exhibits no significnt effect on chemistry vlues. Index of N, 1+, 2+ exhibits no significnt effect on chemistry vlues. Urinlysis 5/18/17 (Order Received) 5/18/17 7:58 AM (Lst Updted) Collection CYSTOCENTESIS Color Clrity YELLOW CLEAR Specific Grvity ph 6.0 Urine Protein 1+ ( mg/dl) Glucose NEGATIVE Ketones NEGATIVE Blood / Hemoglobin Bilirubin Urobilinogen b c NEGATIVE TRACE NORMAL White Blood Cells HPF Red Blood Cells Bcteri 2-5 NONE SEEN HPF Epithelil Cells 1+ (1-2)/HPF Mucus NONE SEEN Csts d OCC HYALINE (0-1)/LPF Generted by VetConnect PLUS My 19, :26 AM Pge 3 of 5

4 PAQUITO RAMIREZ PET OWNER: RAMIREZ DATE OF RESULT: 5/18/17 LAB ID: Urinlysis (continued) Crystls NONE SEEN Other SPERM PRESENT b c d Protein test is performed nd confirmed by the sulfoslicylic cid test. Confirmed by Ictotest Reporting of bcteri morphology hs been dded to your urinlysis results if indicted. For dditionl guidnce on the dignosis nd mngement of urinry trct infections, plese see OCC GRANULAR (0-1)/LPF Endocrinology 5/18/17 (Order Received) 5/18/17 7:58 AM (Lst Updted) Totl T µg/dl Interpretive rnges: <1.0 Low Norml >4.0 High Therpeutic Dogs with no clinicl signs of hypothyroidism nd results within the norml reference rnge re likely euthyroid. Dogs with low T4 concentrtions my be hypothyroid or "euthyroid sick". Occsionlly, hypothyroid dogs cn hve T4 concentrtions tht re low norml. Dogs with clinicl signs of hypothyroidism nd low or low norml T4 concentrtions my be evluted further by submission of free T4 nd cnine TSH. A high T4 concentrtion in cliniclly norml dog is likely vrition of norml; however elevtions my occur secondry to thyroid utontibodies or rrely thyroid neoplsi. For dogs on thyroid supplement, cceptble 4-6 hour post pill totl T4 concentrtions generlly fll within the higher end or slightly bove the reference rnge. Serology 5/18/17 (Order Received) 5/18/17 7:58 AM (Lst Updted) TEST Hertworm Antigen by ELISA RESULT NEGATIVE Generted by VetConnect PLUS My 19, :26 AM Pge 4 of 5

5 PAQUITO RAMIREZ PET OWNER: RAMIREZ DATE OF RESULT: 5/18/17 LAB ID: Serology (continued) TEST RESULT The Americn Hertworm Society recommends tht confirmtory test be run on ll positive ntigen test results prior to therpy, especilly when positive test result is unexpected. For positive result on Hertworm Antigen by ELISA, we recommend submission of new smple for second Hertworm Antigen by ELISA (test code 723) s confirmtory test. Generted by VetConnect PLUS My 19, :26 AM Pge 5 of 5

6 Interpretive Summry Test: Symmetric dimethylrginine A more relible kidney function test Introduction to New Kidney Test: SDMA (pdf) Test dignostic lgorithm (pdf) Description: Test is more relible indictor of kidney function thn cretinine becuse SDMA detects declining kidney function erlier nd is not impcted by muscle mss. Cretinine cn miss erly function loss nd be flsely decresed in ptients with reduced muscle mss. SDMA increses in cute nd ctive injury s well s chronic kidney disese. When SDMA is incresed, ction should be tken. For informtion on recommended ctions, refer to the Test dignostic lgorithm (pdf) which provides informtion on how to Investigte, Mnge nd Monitor kidney disese. For dditionl informtion bout SDMA, plese visit Norml ( 14 µg/dl) Common Cuses Norml SDMA with norml or low cretinine Norml kidney function is likely If SDMA nd/or cretinine is t the upper limit of the reference intervl, erly kidney disese cnnot be ruled out. Evlute complete urinlysis to confirm there is no other evidence of kidney disese. Norml SDMA with high cretinine This combintion of results is rre. If severe hemolysis is present, SDMA results my be decresed by 10-25% in dogs nd 10-20% in cts. SDMA nd cretinine cn both be ffected by biologic nd ssy vribility resulting in fluctutions round the upper end of the reference intervl. This cn be seen with well-mnged stble chronic kidney disese (CKD) nd results will likely lign s disese progresses. Musculr dogs with norml kidney function my hve norml SDMA nd cretinine just exceeding the reference intervl. Assess body condition nd complete urinlysis to help determine significnce of these results. Certin breeds, including greyhounds nd Gret Pyrenees, hve higher cretinine concentrtions thn other breeds nd cretinine results often fll bove the reference intervl while their SDMA concentrtions remin norml. If kidney disese is still suspected, the pet should be evluted for other evidence of kidney disese. A complete urinlysis should be performed to evlute for inpproprite specific grvity, proteinuri or other evidence of kidney disese. Determine if there is supportive history, physicl exmintion findings, bnorml renl imging or other lbortory evidence of kidney disese. Generted by VetConnect PLUS My 19, :26 AM Pge 1 of 5

7 Incresed (>14 µg/dl) Common Cuses High SDMA with norml or low cretinine Renl disese SDMA is more relible indictor of kidney function thn cretinine. SDMA detects declining kidney function erlier. Cretinine cn miss erly function loss. SDMA is not impcted by muscle mss. Cretinine cn be flsely decresed in ptients with poor muscle mss. SDMA increses in cute nd ctive kidney injury s well s CKD. Erly detection with SDMA provides the opportunity to investigte for ctive or cute cuses of kidney injury which might be reversible if identified nd treted promptly. Exmples would include pyelonephritis, cute kidney injury secondry to infectious cuses (e.g. leptospirosis) or drug therpy (e.g. nonsteroidl nti-inflmmtory drugs). Erly identifiction of CKD llows for stging ccording to the Interntionl Renl Interest Society (IRIS) CKD stging guidelines (once determined it is stble), nd erly tretment for the pproprite stge of disese ccording to the IRIS CKD tretment guidelines. For more informtion bout SDMA nd the IRIS CKD guidelines, visit For informtion on ctions to be tken when SDMA is incresed, refer to the Test dignostic lgorithm (pdf) which provides informtion on how to Investigte, Mnge nd Monitor the probble kidney disese. If SDMA is µ g/dl, follow the guidelines below: If there is other evidence of kidney disese, ction should be tken. For informtion on ctions to be tken, refer to the Test dignostic lgorithm (pdf). Other evidence of kidney disese includes supportive history (weight loss, decresed ppetite, polydipsi, polyuri), supportive physicl exmintion findings (plpble kidney bnormlities), nemi, incresed BUN or phosphorus, cretinine incresing within the reference intervl, inpproprite urine specific grvity (<1.030 in dog or <1.035 in ct), proteinuri, ctive urinry sediment, unexplined hypertension nd/or bnorml imging. If there is no other evidence of disese, recheck in 2-4 weeks. If SDMA is persistently µg/dl, regrdless of whether there is other evidence of kidney disese, ction should be tken. For informtion on ctions to be tken, refer to the IDEXX SDMA Test dignostic lgorithm (pdf). If SDMA 20 µg/dl, regrdless of whether there is other evidence of kidney disese, ction should be tken. For informtion on ctions to be tken, refer to the Test dignostic lgorithm (pdf). In puppies, the SDMA reference intervl is 0-16 µg/dl. SDMA reference intervl studies re underwy for kittens nd greyhounds, nd results my lso be slightly higher nd should be interpreted in light of other findings. High SDMA with high cretinine Renl disese Kidney disese is probble nd ction should be tken. For informtion on ctions to be tken, refer to the Test dignostic lgorithm (pdf). Confirm tht there is other evidence of kidney disese such s supportive history, bnorml kidney plption, inpproprite urine specific grvity, proteinuri, nd/or bnorml imging. Infectious, inflmmtory, toxic nd ischemic renl diseses re most common. Uncommon Cuses High SDMA with high cretinine Renl disese Congenitl kidney disese, myloidosis, nd renl neoplsi re less common. Dehydrtion If dehydrtion results in reduction in glomerulr filtrtion rte (GFR) nd prerenl zotemi, then SDMA should increse long with cretinine. Assess hydrtion sttus nd urine specific grvity for evidence of dehydrtion. Generted by VetConnect PLUS My 19, :26 AM Pge 2 of 5

8 Postrenl If ureterl or urethrl obstruction results in decrese in GFR, then SDMA will increse long with cretinine. Relted Findings Renl disese Incresed BUN, cretinine nd phosphorus SDMA cn be incresed prior to development of zotemi Electrolyte bnormlities, metbolic cidosis, hypo- or hyperclcemi Mild to moderte nonregenertive nemi Inpproprite urine specific grvity Urinry csts, pyuri, hemturi, proteinuri, microlbuminuri, glucosuri, bcteriuri Positive urine culture Incresed blood pressure Protein-losing nephropthy (glomerulonephritis or myloidosis) Decresed lbumin Incresed urine protein:cretinine rtio High cholesterol in nephrotic syndrome Positive PCR or serology for leptospirosis, Lyme disese, ehrlichiosis, or other infections Abnorml kidney imging findings such s bnorml renl size nd/or structure History of kidney toxin exposure Additionl Informtion Physiology SDMA is molecule formed by posttrnsltionl methyltion of the mino cid L-rginine in the nucleus of cells by the protein-rginine methyltrnsferse enzymes. During protein degrdtion these methylted rginine molecules re relesed. Biologiclly, SDMA is considered n inert molecule. SDMA is eliminted by renl excretion; therefore, blood concentrtions re ffected by chnges in GFR, mking SDMA good mrker for kidney disese. SDMA is biomrker for kidney function nd hs been shown to rise in proportion to cretinine nd is inversely relted to GFR (mesured by iohexol clernce) in dogs nd cts with kidney disese. SDMA increses erlier thn cretinine in dogs nd cts with kidney disese. SDMA increse in cute nd ctive kidney disese s well s chronic kidney disese. SDMA increses on verge with 40% loss of kidney function versus cretinine, which does not increse until up to 75% of kidney function is lost. In cts with CKD, SDMA increses on verge of 17 months before cretinine. In dogs with CKD, SDMA increses on verge of 9.8 months before cretinine. SDMA is not impcted by len body mss. Reductions in len body mss occur with ging, nd chronic disese cn lower cretinine concentrtions, but SDMA increses s kidney function declines with no correltion to len body mss. SDMA is more relible indictor of kidney function in cts with hyperthyroidism becuse SDMA is not impcted by len muscle mss nd ppers to be less impcted by hyperfiltrtion. SDMA is specific for kidney function. It is not impcted by vrious diseses including liver disese, Cushing's disese nd hert disese, unless there is concurrent kidney disese. It does not chnge postprndilly unlike cretinine which cn be rtificilly incresed postprndilly especilly fter ingestion of met. Week-to-week vribility of iohexol clernce, serum cretinine nd SDMA re similr in dogs with stble renl disese. In puppies, SDMA reference intervl is 0-16 µg/dl. SDMA reference intervl studies re underwy for kittens nd greyhounds, nd results my lso be slightly higher nd should lwys be interpreted in light of other findings. Generted by VetConnect PLUS My 19, :26 AM Pge 3 of 5

9 Dignostic Methodology The Test is vlidted for veterinry use for both cts nd dogs per Clinicl Lbortory Improvement Amendments (CLIA) guidelines. The test uses ptented nd proprietry ntibody tht requires no chemicl pretretment of specimens nd specificlly binds to SDMA for consistent nd ccurte mesurement. Over the lst five yers, IDEXX hs invested over $400 million in reserch nd development in order to bring you innovtions like the Test. is mesured t IDEXX Reference Lbortories using high throughput immunossy. No informtion is currently vilble on how to interpret SDMA in species other thn dogs nd cts. SDMA cn be performed on serum or lithium heprin or EDTA plsm. SDMA is stble for 4 dys t room temperture nd 14 dys refrigerted. It is lso stble for yers in specimens tht remin frozen nd do not undergo freeze-thw cycles. Lipemi nd icterus do not ffect SDMA results. Severe hemolysis my slightly decrese SDMA (10-25% in dogs; 10-20% in cts). Rrely in specimens with severe hemolysis nd lipemi, SDMA cnnot be mesured. References Brff J, Aguir J, Yerrmilli M, et l. Anlysis of Serum Symmetric Dimethylrginine Concentrtion in Ptient Smples Identified Through Retrospective Trending of Serum Cretinine. [ACVIM Abstrct U-43] J Vet Intern Med. 2014; 28(3): Brff J, Obre E, Yerrmilli M, et l. Reltionship Between Serum Symmetric Dimethylrginine Concentrtion nd Glomerulr Filtrtion Rte in Cts. J Vet Intern Med. 2014, Vol 28: Hll JA, Yerrmilli M, Obre E, et l. Comprison of Serum Concentrtions of Symmetric Dimethylrginine nd Cretinine s Kidney Function Biomrkers in Cts with Chronic Kidney Disese. J Vet Intern Med. 2014; 28: Hll JA, Yerrmilli M, Obre E, Yerrmilli M, Almes K, Jewell DE. "Serum Concentrtions of Symmetric Dimethylrginine nd Cretinine in Dogs with Nturlly-Occurring Chronic Kidney Disese." J Vet Intern Med. 2016; 30(3): Hll JA, Yerrmilli M, Obre E, et l. Comprison of Serum Concentrtions of Symmetric Dimethylrginine nd Cretinine s Kidney Biomrkers In Helthy Geritric Cts Fed Reduced Protein Foods Enriched with Fish Oil, L-crnitine, nd Medium Chin Triglycerides. Vet J. 2014; 202: Hll JA, Yerrmilli M, Obre E, et l. "Reltionship Between Len Body Mss nd Serum Renl Biomrkers in Helthy Dogs." J Vet Intern Med. 2015; 29(3): Jepson, RE, Syme HM, Vllnce C, et l. Plsm Asymmetric Dimethylrginine, Symmetric Dimethylrginine, L-Arginine, nd Nitrite/Nitrte Concentrtions in Cts with Chronic Kidney Disese nd Hypertension. J Vet Intern Med. 2008; 22: Jewell DE, Fritsch D, Yerrmilli M, et l. Feeding Reduced Protein nd Phosphorus Food to Dogs with Nturlly Occurring Renl Disese Reduces Serum Concentrtions of Cretinine nd Symmetric Dimethylrginine (SDMA). [ACVIM Abstrct NU-27]. J Vet Intern Med. 2014; 28(3): p Jewell DE, Yerrmilli M, Obre E, et l. Foods with Controlled Protein nd Phosphorus nd Enhnced with Antioxidents Vitmin E nd C Reduce Circulting Ure nd Symmetricl Di-Methyl Arginine, nd Increse Isosine in Dogs. [ACVIM Abstrct NM-10]. J Vet Intern Med. 2013; 27(3): p744. Jewell DE, Yerrmilli M, Obre E, et l. Incresing Dietry Protein Concentrtion from 15% to 30% in One Yer Study Increses Glomerulr Filtrtion Rte nd Reduces Cretinine nd Symmetricl Di-Methyl Arginine. [ACVIM Abstrct NM-9]. J Vet Intern Med. 2013; 27(3): p744. Nbity MB, Lees GE, Boggess M, et l. "Symmetric Dimethylrginine Assy Vlidtion, Stbility, nd Evlution s Mrker for Erly Detection of Chronic Kidney Disese in Dogs." J Vet Intern Med. 2015; 29(4): Nbity MB, Lees GE, Boggess M, et l. Week to Week Vribility of Iohexol Clernce, Serum Cretinine, nd Symmetric Dimethylrginine in Dogs with Stble Chronic Renl Disese. [ACVIM Abstrct NU-14]. J Vet Intern Med. 2013; 27(3): 734. Nbity MB, Lees GE, Boggess M, et l. "Symmetric Dimethylrginine Assy Vlidtion, Stbility, nd Evlution s Mrker for the Erly Detection of Chronic Kidney Disese." J Vet Intern Med. 2015; 29(4): Pdmnbhn M, Obre E, Yerrmilli M. LCMS Method Development nd Vlidtion for Potentil Chronic Kidney Disese Mrker Symmetricl Dimethyl Arginine. [ACVIM Abstrct NU-21]. J Vet Intern Med. 2013; 27(3): 736. Generted by VetConnect PLUS My 19, :26 AM Pge 4 of 5

10 Ptch D, Obre E, Xie H, et l. "High Throughput Immunossy Tht Correltes to Gold Stndrd Liquid Chromtogrphy-Mss Spectrometry (LC-MS) Assy for the Chronic Kidney Disese (CKD) Mrker Symmetric Dimethylrginine (SDMA)." [ACVIM Abstrct NU-19]. J Vet Intern Med. 2015; 29(4):1216. Prusevich P, Ptch D, Obre E, et l. "Vlidtion of Novel High Throughput Immunossy for the Quntittion of Symmetric dimethylrginine (SDMA)" [AACC Abstrct B-048]. Clin Chem. 2015; 61(S10):S135. Rentko V, Nbity M, Yerrmilli M, et l. Determintion of Serum Symmetric Dimethylrginine Reference Limit in Cliniclly Helthy Dogs. [ACVIM Abstrct P-7]. J Vet Intern Med. 2013; 27(3): 750. Lst Updted 2/1/2017 Generted by VetConnect PLUS My 19, :26 AM Pge 5 of 5