CHARLIE HASSID. Hematocrit SDMA WBC ALT. Creatinine BUN ALP. Hematology. Species: Canine Gender: Male Year of Birth: 2005 Client: HASSID

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1 CARIE ASSID Species: Cnine Gender: Mle Yer of Birth: 2005 Client: ASSID Requisition #: 295 Accession #: Account Code: 6550 Veterinrin: AKAMIAN, ASKAN Pnel/Profile: Senior Screen- Stndrd CBC SAMPE/TEST INFO NEEDED RETICUOCYTE PANE emtocrit WBC SDMA 0 BUN Cretinine AT AP emtology 5/13/2016 (Order Received) 4/28/2016 4/27/2016 7:34 AM (st Updted) 10:24 AM RBC M/µ emtocrit % emoglobin g/d MCV f MC pg Generted by VetConnect PUS My 13, :58 AM Pge 1 of 5

2 CARIE ASSID emtology (continued) MCC g/d % Reticulocyte 1.7 % Reticulocyte K/µ Reticulocyte Comment A reticulocyte count of greter thn 110 K/u of blood is considered evidence of bone mrrow response to n incresed peripherl demnd. Depending on the degree of nemi, reticulocyte count <110 K/u my indicte n indequte bone mrrow response. Seril monitoring of the erythrogrm nd reticulocyte count my be useful to evlute bone mrrow responsiveness over time. The following chrt my be used s guideline to determine ppropriteness of regenertive response. Degree of bone mrrow response (K/u): Mild Moderte Mrked >300 A reticu... WBC K/µ % Neutrophil 68.3 % % ymphocyte 17.5 % % Monocyte 9.3 % % Eosinophil 4.8 % % Bsophil 0.1 % Neutrophil K/µ ymphocyte K/µ Monocyte K/µ Eosinophil K/µ Bsophil K/µ Pltelet K/µ Polychromsi Anisocytosis SIGT SIGT SIGT Remrks SIDE REVIEWED MICROSCOPICAY. SIDE RE... Chemistry 5/13/2016 (Order Received) 4/28/2016 4/27/2016 7:34 AM (st Updted) 12:19 PM Glucose mg/d BUN mg/d Cretinine mg/d SDMA BUN:Cretinine Rtio µg/d Phosphorus mg/d Generted by VetConnect PUS My 13, :58 AM Pge 2 of 5

3 CARIE ASSID Chemistry (continued) Clcium mg/d Sodium mmol/ Potssium mmol/ N:K Rtio Chloride mmol/ TCO2 (Bicrbonte) mmol/ 20 Anion Gp mmol/ 25 Totl Protein g/d Albumin g/d Globulin g/d Alb:Glob Rtio AT U/ AST U/ 50 AP U/ GGT U/ Bilirubin - Totl mg/d Bilirubin - Unconjugted Bilirubin - Conjugted mg/d mg/d 0.0 Cholesterol mg/d Cretine Kinse U/ 450 emolysis Index b N + ipemi Index c N N BOT SDMA AND CREATININE ARE WITIN TE REFERENCE INTERVA which indictes kidney function is likely good. If SDMA nd/or cretinine is t the upper end of the reference intervl, erly kidney disese cnnot be ruled out. Evlute complete urinlysis to confirm there is no other evidence of kidney disese. b Index of N,+,++ exhibits no significnt effect on chemistry vlues. c Index of N,+,++ exhibits no significnt effect on chemistry vlues. Endocrinology 5/13/2016 (Order Received) 4/28/2016 7:34 AM (st Updted) Totl T µg/d 1.4 Generted by VetConnect PUS My 13, :58 AM Pge 3 of 5

4 CARIE ASSID Interpretive rnges: <1.0 ow Norml >4.0 igh 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 TS. 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. Other 5/13/2016 (Order Received) 7:34 AM (st Updted) SAMPE / TEST INFO NEEDED A urine specimen ws not received. The reminder of requested testing hs been performed. Thnk You. Cncelled 5/13/2016 (Order Received) 7:34 AM (st Updted) Collection Color Clrity Specific Grvity p Protein Glucose Ketones Blood / emoglobin Bilirubin Urobilinogen White Blood Cells 0-5 PF Generted by VetConnect PUS My 13, :58 AM Pge 4 of 5

5 CARIE ASSID Cncelled (continued) Red Blood Cells Bcteri 0-5 PF Epithelil Cells Mucus Csts Crystls Other Protein test is performed nd confirmed by the sulfoslicylic cid test. Generted by VetConnect PUS My 13, :58 AM Pge 5 of 5

6 SDMA (Symmetric Dimethylrginine) Interpretive Summry Description: Symmetric dimethylrginine (SDMA) is new kidney function test. It increses erlier thn cretinine in some nimls with chronic kidney disese (CKD). Unlike cretinine, SDMA is not impcted by len body mss giving it the potentil to be more sensitive indictor of kidney function s CKD progresses nd the pet loses weight. SDMA nd cretinine should be interpreted together, long with urinlysis. For dditionl informtion bout SDMA, plese visit Norml SDMA ( 14 µg/d) Common Cuses Norml SDMA with norml or low Cretinine o 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 o Kidney disese is possible If SDMA is t or very ner the upper limit of the reference intervl, biologic nd ssy vribility my be contributing to the rre incidence of norml SDMA in fce of high cretinine. SDMA nd cretinine results will likely lign with repet testing over time. Determine if there is other evidence of kidney disese such s supportive history, bnorml kidney plption, inpproprite urine specific grvity, proteinuri nd/or bnorml imging. o 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. o Certin breeds, including Greyhounds nd Gret Pyrenees, hve higher cretinine concentrtion thn other breeds nd cretinine results often fll bove the reference intervl while their SDMA concentrtions remin norml. o SDMA results my be depressed by 10-25% in dogs nd 10-20% in cts if severe hemolysis is present. Incresed SDMA (>14 µg/d) Common Cuses igh SDMA with norml or low Cretinine o Renl Disese Erly kidney disese is likely SDMA increses erlier thn cretinine in erly renl disese. Most nimls with erly kidney disese hve n SDMA between μg/d. Since SDMA increses s kidney function decreses, SDMA > 20 μg/d re typiclly seen in more dvnced disese long with n incresed cretinine. An incresed SDMA with norml cretinine my be seen in nimls with reversible kidney dmge if the underlying cuse is identified or resolves on its own. Exmples would include pyelonephritis, cute kidney injury secondry to infectious (e.g. leptospirosis) or drug therpy (e.g. nonsteroidl ntiinflmmtory drugs). In poorly muscled nimls, cretinine my be poor indictor of renl function. SDMA is more sensitive indictor of kidney function in poorly muscled nimls. Infectious, inflmmtory, toxic nd ischemic renl diseses re most common. Generted by VetConnect PUS: My 13, :58 AM Symmetric Dimethylrginine (SDMA) Pge 1 of 4

7 o SDMA results my be slightly higher (~1 μg/d) in puppies, kittens nd Greyhounds nd results should be interpreted in light of other findings. o Evlute for other evidence of kidney disese such s supportive history, bnorml kidney plption, inpproprite urine specific grvity, proteinuri nd/or bnorml imging. igh SDMA with high Cretinine o Renl Disese Kidney function is likely impired Infectious, inflmmtory, toxic nd ischemic renl diseses re most common. 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. Uncommon Cuses igh SDMA with high Cretinine o Renl Disese Congenitl kidney disese, myloidosis, nd renl neoplsi re less common cuses of renl disese. o Dehydrtion If dehydrtion results in prerenl zotemi reflecting reduction in glomerulr filtrtion rte (GFR), then SDMA should lso increse long with cretinine. Assess hydrtion sttus nd urine specific grvity for evidence of dehydrtion. o Post-renl If ureterl or urethrl obstruction results in decrese in GFR, then SDMA will increse long with cretinine. Relted Findings Renl disese o Incresed BUN, cretinine nd phosphorus SDMA cn be incresed prior to development of zotemi o Electrolyte bnormlities, metbolic cidosis, hypo- or hyperclcemi o Mild to moderte nonregenertive nemi o Inpproprite urine specific grvity. o Urinry csts, pyuri, hemturi, proteinuri, microlbuminuri, glucosuri, bcteriuri o Positive urine culture o Incresed blood pressure o Protein losing nephropthy (glomerulonephritis or myloidosis) Decresed lbumin Incresed urine protein:cretinine rtio igh cholesterol in nephrotic syndrome o Positive PCR or serology for leptospirosis, yme disese, ehrlichiosis or other infections o Abnorml kidney imging findings such s bnorml renl size nd/or structure o istory of kidney toxin exposure Additionl Informtion Physiology SDMA is molecule formed by post-trnsltionl methyltion of the mino cid -rginine in the nucleus of cells by protein-rginine methyltrnsferse enzymes. o During protein degrdtion these methylted rginine molecules re relesed. o 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 renl disese. Generted by VetConnect PUS: My 13, :58 AM Symmetric Dimethylrginine (SDMA) Pge 2 of 4

8 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 chronic kidney disese. o SDMA increses on verge with 40% loss of kidney function versus cretinine, which does not increse until 75% of kidney function is lost. o In cts, SDMA increses on verge of 17 months before cretinine. o In dogs, SDMA increses on verge of 9.5 months before cretinine. 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 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. Week to week vribility of iohexol clernce, serum cretinine nd SDMA re similr in dogs with stble renl disese SDMA results my be slightly higher (~1 μg/d) in puppies, kittens nd Greyhounds with norml kidney function. Dignostic Methodology No informtion is currently vilble on how to interpret SDMA in species other thn dogs nd cts. SDMA is mesured t IDEXX Reference bortories using high throughput immunossy. SDMA cn be performed on serum or lithium heprin 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. ipemi, hemolysis 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. Reference 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: ll 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, Vol 28: ll JA, Yerrmilli M, Obre E, et l. Comprison of Serum Concentrtions of Symmetric Dimethylrginine nd Cretinine s Kidney Biomrkers In elthy Geritric Cts Fed Reduced Protein Foods Enriched with Fish Oil, - crnitine, nd Medium Chin Triglycerides. Vet J. 2014, Vol 202: ll 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 M, Vllnce C, et l. Plsm Asymmetric Dimethylrginine, Symmetric Dimethylrginine, - Arginine, nd Nitrite/Nitrte Concentrtions in Cts with Chronic Kidney Disese nd ypertension. J Vet Intern Med Vol 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, ees GE, Boggess M, et l. Correltion of Symmetric Dimethylrginine with Glomerulr Filtrtion Rte in Dogs with Chronic Progressive Renl Disese. [ACVIM Abstrct NU-11]. J Vet Intern Med. 2013; 27(3): 733. Nbity MB, ees 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. Generted by VetConnect PUS: My 13, :58 AM Symmetric Dimethylrginine (SDMA) Pge 3 of 4

9 Nbity MB, ees 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. CMS 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. Ptch D, Obre E, Xie, et l. igh Throughput Immunossy Tht Correltes to Gold Stndrd iquid Chromtogrphy-Mss Spectometry (C-MS) Assy for the Chronic Kidney Disese (CKD) Mrker Symmetric Dimethylrginine (SDMA). J Vet Intern Med. 2015; pg. 95. Erly View, Article first published online: 27 MAY DOI: /jvim Rentko V, Nbity M, Yerrmilli M, et l. Determintion of Serum Symmetric Dimethylrginine Reference imit in Cliniclly elthy Dogs. [ACVIM Abstrct P-7]. J Vet Intern Med. 2013; 27(3): 750. Yerrmilli M, Yerrmilli M, Obre E, et l. Symmetric Dimethylrginine (SDMA) Increses Erlier thn Serum Cretinine in Dogs with Chronic Kidney Disese (CKD). [ACVIM Abstrct NU-42]. J Vet Intern Med. 2014; 28(3): st Updted 11/18/2015 Generted by VetConnect PUS: My 13, :58 AM Symmetric Dimethylrginine (SDMA) Pge 4 of 4