Diagnostic value of the rectal ammonia tolerance test, fasting plasma ammonia and fasting plasma bile acids for canine portosystemic shunting

BackgroundIn dogs with congenital portosystemic shunt (CPSS), recovery after surgical CPSS attenuation is difficult to predict.ObjectivesOur aim was to build a model with plasma albumin concentration and mRNA expression levels of hepatic gene products as predictors of recovery from portosystemic shunting after surgery.AnimalsSeventy‐three client‐owned dogs referred for surgical attenuation of CPSS.MethodsA prediction model was constructed using 2 case‐control studies of recovered and nonrecovered dogs after surgical CPSS attenuation. In the 1st study, a dog‐specific gene expression microarray analysis was used to compare mRNA expression in intraoperatively collected liver tissue between 23 recovered and 23 nonrecovered dogs. In the 2nd study, preoperative plasma albumin concentration and the expression of microarray‐selected genes were confirmed by RT‐qPCR in intraoperatively collected liver samples of 31 recovered and 31 nonrecovered dogs, including 35 dogs from the 1st study.ResultsIn the 1st study, 43 genes were differently expressed in recovered and nonrecovered dogs. The mean preoperative plasma albumin concentration in recovered dogs was higher compared to nonrecovered dogs (23 and 19 g/L, respectively; P = .004). The best fitting prediction model in the 2nd study included preoperative plasma albumin concentration and intraoperative DHDH, ERLEC1, and LYSMD2 gene expression levels.Conclusion and Clinical ImportanceA preclinical model was constructed using preoperative plasma albumin concentration and intraoperative hepatic mRNA expression of 3 genes that were unbiasedly selected from the genome to predict recovery from portosystemic shunting after shunt ligation. Further development is essential for clinical application.

Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Genome‐wide based model predicting recovery from portosystemic shunting after liver shunt attenuation in dogs

Bossche

Steenbeek

Weber

et al. 2018

“…The most commonly used indicators of hepatobiliary disease are plasma liver enzyme activity and preprandial bile acid concentrations (BA) . Alanine aminotransferase (ALT) is a liver specific cytosolic enzyme and a sensitive indicator for hepatocellular injury .…”

mentioning

confidence: 99%

Sensitivity and Specificity of PlasmaALT,ALP, and Bile Acids for Hepatitis in Labrador Retrievers

Dirksen

Burgener

Rothuizen

et al. 2017

Self Cite

BackgroundBiochemical indicators for diagnosing liver disease are plasma alanine aminotransferase activity (ALT), alkaline phosphatase activity (ALP), and bile acid concentration (BA).ObjectivesTo determine the sensitivity and specificity of ALT, ALP, and BA for detecting primary hepatitis (PH) in clinically healthy Labrador retrievers and investigate whether ALT and ALP can discriminate between dogs with PH and nonspecific reactive hepatitis (RH).Animals191 clinically healthy and 51 clinically ill Labrador retrievers with hepatic histopathology.MethodsRetrospective study. Medical records were reviewed for ALT, ALP, preprandial BA, liver histopathology, and hepatic copper concentrations.ResultsIn 64% (122/191) of the clinically healthy Labrador retrievers, hepatic histology revealed inflammatory infiltrates. This frequency might be biased because part of them was included as first‐line relatives of dogs with copper‐associated hepatitis. Sensitivity of ALT, ALP, and BA in this population for detecting acute hepatitis was 45, 15, and 15%, respectively. For chronic hepatitis, sensitivity was 71, 35, and 13%, respectively. Specificity of ALT, ALP, and BA was >90% for AH, CH, and RH. When increased liver enzymes were present, median ALT was significantly higher in PH cases (312 U/L, range 38–1,369) compared to RH cases (91 U/L, range 39–139) (P < .001). There was no difference in ALP between dogs with a PH and a RH (P = .361).Conclusions and Clinical ImportanceHistopathologic abnormalities in the liver were present in the majority of apparent clinically healthy Labrador retrievers. The sensitivity of ALT, ALP, and BA for detecting acute and chronic hepatitis in this population was low. More sensitive biomarkers are needed for early detection of liver disease in apparent clinically healthy dogs.

“…Hyperammonemia in dogs is mostly secondary to congenital portosystemic shunts (CPSS) . These CPSS are vascular anomalies that connect the portal vein to the systemic circulation, thereby bypassing the hepatic sinusoids .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of orally administered sodium benzoate and sodium phenylbutyrate in dogs with congenital portosystemic shunts

Straten

Dalen

Mesu

et al. 2019

Background Hyperammonemia can result in hepatic encephalopathy, which in severe cases eventually can lead to coma and death. In dogs, congenital portosystemic shunts (CPSS) are the most common cause for hyperammonemia. Conservative treatment consists of a protein modified diet, nonabsorbable disaccharides, antibiotics, or some combinations of these. Sodium benzoate (SB) and sodium phenylbutyrate (SPB) both are used in the acute and long‐term treatment of humans with hyperammonemia caused by urea cycle enzyme deficiencies. Both treatments are believed to lower blood ammonia concentrations by promoting excretion of excess nitrogen via alternative pathways. Objectives To evaluate the efficacy and safety of PO treatment with SB and SPB on hyperammonemia and clinical signs in CPSS dogs. Methods Randomized, double‐blind, placebo‐controlled crossover trial. Concentrations of blood ammonia and bile acids were measured in CPSS dogs before and after a 5‐day treatment with SB, SPB, and placebo. A wash‐out period of 3 days was used between treatments. A standard questionnaire was developed and distributed to owners to evaluate clinical signs before and after each treatment. Results Blood ammonia concentrations were not influenced by any of the treatments and were comparable to those observed during placebo treatment. In addition, SB and SPB treatment did not result in improvement of clinical signs. Adverse effects during treatment included anorexia, vomiting, and lethargy. Conclusions and Clinical Importance Based on our results, we conclude that SB or SPB are not useful in the conservative treatment of hyperammonemia in dogs with CPSS.