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The Utility of Uric Acid Assay in Dogs As an Indicator of Functional Hepatic Mass

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The Utility of Uric Acid Assay in Dogs As an Indicator of Functional Hepatic Mass Article — Artikel The utility of uric acid assay in dogs as an indicator of functional hepatic mass J M Hilla*, A L Leisewitza and A Goddarda We believe that UA deserved a re- ABSTRACT assessment as a test of liver function. Uric acid was used as a test for liver disease before the advent of enzymology. Three old Plasma ammonia concentration is a very studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine reliable test of liver function but has very metabolism in the liver,deserved re-evaluation as a liver function test. Serum total bile acids stringent sample-handling requirements are widely accepted as the most reliable liver function test. This study compared the ability that often make its application in the of serum uric acid concentration to assess liver function with that of serum pre-prandial bile 2,8,9,33,35 acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also com- average clinic setting impractical . pared in a renal disease group. Using a control group of healthy dogs, a group of dogs with The provocative ammonia-tolerance test, 15 congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver which is used to increase sensitivity , has diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was inherent risks of inducing hepatic ence- compared to detect reduced functional hepatic mass overall and in the vascular or paren- phalopathy in dogs with subclinical liver chymal liver disease groups separately. Sensitivities, specificities and predictive value disease when administered at the chal- parameters were calculated for each test. The medians of uric acid concentration did not lenge dose16,31. Basal serum bile acid con- differ significantly between any of the groups, whereas pre-prandial bile acids medians centrations, while not as sensitive or were significantly higher in the liver disease groups compared with the normal and renal specific for portosystemic shunts as am- disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65 % monia, are easier to perform and also while the specificity of uric acid in detecting liver disease overall was 59 %. The sensitivity more useful in non vascular-associated and specificity of uric acid in detecting congenital vascular liver disease was 68 % and 59 %, liver disease1,3,5,11,13,20,32. However, bile acid respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver assays are not widely available in South disease was 63 % and 60 %, respectively. The overall positive and negative predictive values Africa resulting in delays in turn-around for uric acid in detecting liver disease were poor and the data in this study indicated uric times. Post-prandial bile acid tests in- acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route crease the sensitivity of the bile acid assay, of excretion. particularly in diagnosing portosystemic shunts, but the 2-hour delay (post-pran- Keywords: bile acids, dog, hepatic function, uric acid. dially) is often not practical in a busy prac- Hill J M, Leisewitz A L, Goddard A The utility of uric acid assay in dogs as an indicator of tice setting. functional hepatic mass. Journal of the South African Veterinary Association (2011) 82(2): 86–93 In today’s climate of ever-increasing (En.). Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, costs, and demand for rapid turn-around University of Pretoria, Private Bag X04, Onderstepoort, 0110 South Africa. times, it would be very useful to veteri- narians if a simple, rapid, cheap and robust assay could be found for evaluat- INTRODUCTION the publication of 2 studies and 1 case ing functional hepatic mass. UA would Physiologically, uric acid is an attractive report in the late 1950s12,19,22. One of the appear to have this potential and is per- candidate for a liver function test. In most studies compared UA with bromosulpho- formed by most medical laboratories. The mammalian species uric acid (UA) is the thalein in experimental carbon-tetra- purpose of this study was to compare the end-point of purine metabolism in the chloride hepatotoxicosis22. The case utility of serum UA concentrations com- liver4,14,24,30. In most mammals, and in dogs report and other study compared UA with pared with the concentration of serum in particular, the UA is then decarboxy- liver enzymes, particularly alkaline pre-prandial or baseline bile acids (b-BA) lated producing allantoin, which is water- phosphatase (ALP)12,19. Subsequent anal- as a screening test to assess liver function soluble and can be excreted by the ysis of these studies identified some in dogs with liver disease, and to assess kidneys10,14,24,30. In these species serum UA shortcomings, including inconsistencies UA in dogs with renal disease and a con- levels only increase to the levels encoun- in definition of liver disease, the lack of trol group of healthy dogs. tered in humans when there is hepatic histopathological confirmation of liver The hypotheses were as follows: (1) uric dysfunction4,7,10,14,24,30. However,UA is pre- pathology and the fact that UA and ALP acid is an effective test of liver function in dominantly excreted in the urine were compared despite not having been dogs with both vascular and non-vascular and could be affected by renal insuffi- run on the same sample. In addition, when liver disease; (2) renal compromise does ciency17,18,21,23,25,36. these studies were published the differ- not result in elevated serum UA concen- UA was used as a liver test in the late ences between liver function tests and tration. 1950s and early 1960s. UA fell out of liver enzymes were not always emphasised favour as a liver function test following and UA, a liver function test, was com- MATERIALS AND METHODS 12,19,22 aDepartment of Companion Animal Clinical Studies, pared with liver enzymes . Despite Faculty of Veterinary Science, University of Pretoria, the limitations of these studies, several Data collection Private Bag X04, Onderstepoort, 0110 South Africa. prominent reference texts have since per- A group of dogs, determined to be clini- *Author for correspondence. E-mail: [email protected] petuated their findings and UA fell out of cally healthy based on a clinical examina- 4,6,7 Received: June 2010. Accepted: May 2011. favour as a test of liver function . tion, haematology and biochemistry 86 0038-2809 Tydskr.S.Afr.vet.Ver. (2011) 82(2): 86–93 Table 1: Descriptive statistics of mean and medians for the variables that were used for case selection and comparison in the 4 groups. Group 1, control group; Group 2, portosystemic shunt group; Group 3, liver disease group; Group 4, renal disease group. Group Statistic Age Mass Alt 14–66 Alp 56–113 Urea 36–8.9 Creat 70–130 Pre-BA <15 Post-BA <25 UA <0.06 Urine SG (Ref.Ran) (U/ ) (U/ ) (mmol/ ) (µmol/ ) (µmol/ ) (µmol/ ) (µmol/ ) (SI Units) 1 Median 18 15.2 27 81 6 83 9.24 23.82 0.06 Mean 29.2 15.83 31.24 89.24 6.26 84.96 9.57 26.76 0.06 2 Median 7 7.8 76.5 161.5 2.8 50.5 48.2 202.5 0.07 Mean 7.21 10.24 85.1 239.31 3.68 51.25 93.46 247.03 0.074 3 Median 94 8.6 64 341 6 80 45.01 66.04 0.07 Mean 86.89 12.23 378.17 893.35 7.58 84.86 67.72 88.16 0.092 4 Median 60 28.10 78 152.5 62.6 532 17.02 0.06 1.015 Mean 69.42 26.45 82.5 219.75 64.44 797.08 16.96 0.08 1.015 panels was included as a healthy control failure based on serum urea and creati- cluded STATISTICA® (Release 7), BMDP group (Group 1). The biochemistry panel nine concentrations. Group 3 consisted of Statistical Software® (Release 7.1) and included urea, creatinine, electrolytes dogs that had biochemical indications of SAS® (version 9.1). The Kruskal-Wallis (Na, K, Cl), total protein, albumin, ALT, liver disease, raised baseline bile acids method was used to compare the medians ALP, GGT calcium, inorganic phosphate, and ultrasound and/or histopathological of UA, b-BA and pp-BA from all 4 groups. pre- and post-prandial bile acids, and uric evidence of liver disease that was not Chi-square analysis was used to test for acid. Dogs were included in this group if vascular associated. Dogs were included any relationship between UA and b-BA. they had serum baseline bile acid concen- if they had elevated liver enzymes, ele- The P value indicative of significance was trations within normal limits (<15 µmol/ ). vated bile acid concentrations and no P < 0.05 Dalmatians and Bulldogs were excluded evidence of renal compromise based on from any of the disease groups because of serum urea and creatinine concentra- Group selection possible hyperuricaemia due to defective tions. Members of Group 4 were included Group 1 consisted of 25 dogs, of which hepatic uric acid metabolism28,29. if they had elevated serum urea and 11 were females and 14 were males Retrospective case data from the data creatinine concentrations, ultrasound or (Table 2). The age range was from 5 to base of the Clinical Pathology Laboratory histopathology results indicating renal 84 months with a median age of 18 of the Onderstepoort Veterinary Academic failure and no evidence of raised liver en- months.
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