The effects of age and sex on reference intervals for cobalamin, homocysteine, and serum and urinary methylmalonic acid in healthy adult dogs

Abstract Background In dogs, data on reference intervals (RIs) for cobalamin, markers of metabolism (markersB12met), age and sex effects are limited. Hypothesis/Objectives Establish RI for serum cobalamin, homocysteine, and methylmalonic acid (sMMA) concentrations, urinary methylmalonic acid‐to‐crea...

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Main Authors: Anna‐Lena Proksch, Sophia Schaefer, Vanessa Dreller, Judith Langenstein, Ralph Fingerhut, Natali Bauer, Andreas Moritz
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of Veterinary Internal Medicine
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Online Access:https://doi.org/10.1111/jvim.17250
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author Anna‐Lena Proksch
Sophia Schaefer
Vanessa Dreller
Judith Langenstein
Ralph Fingerhut
Natali Bauer
Andreas Moritz
author_facet Anna‐Lena Proksch
Sophia Schaefer
Vanessa Dreller
Judith Langenstein
Ralph Fingerhut
Natali Bauer
Andreas Moritz
author_sort Anna‐Lena Proksch
collection DOAJ
description Abstract Background In dogs, data on reference intervals (RIs) for cobalamin, markers of metabolism (markersB12met), age and sex effects are limited. Hypothesis/Objectives Establish RI for serum cobalamin, homocysteine, and methylmalonic acid (sMMA) concentrations, urinary methylmalonic acid‐to‐creatinine ratio (uMMA:crea), and determine effects of sex and age. Methods Prospective study using healthy dogs (1‐10 years). Cobalamin and markersB12met were determined using chemiluminescence immunoassay (cobalamin) and liquid chromatography/tandem mass spectrometry (homocysteine, sMMA, uMMA:crea). In dogs with outlying data, changes in health, markersB12met, and onset of gastrointestinal signs were reevaluated after 9‐15 months. Results Twelve of 120 healthy dogs had abnormal uMMA:crea ratios. No other cobalamin analyte outliers were found. Outlying data re‐examination (odRE) was performed in 10/12 dogs. Chronic gastrointestinal signs occurred in 64% of odRE‐dogs, whereas 36% remained healthy. In total, 112 dogs (67 females, 45 males; median ages, 3.5 and 3.75 years, respectively) were included in RI analyses. Reference intervals were 178.5‐851 pmol/L (cobalamin), 5.8‐29.0 μmol/L (homocysteine), 45.3‐159.5 μg/L (sMMA), and ≤22.4 mg/g (uMMA:crea). Only age affected cobalamin concentrations (significant decrease). Compared by sex and neuter status, intact male dogs had significantly higher uMMA:crea ratios (median, 13.5; range, 1.9‐83.6 mg/g) than the other groups (median, 2.5; range, 0.7‐9.7 mg/g; P < .0001). Sex‐specific RI were ≤58.9 mg/g (intact male) vs ≤5.2 mg/g (females and neutered males). Conclusion and Clinical Importance Intact male dogs had significantly higher uMMA:crea ratios than the other groups. Thus, sex‐specific RI are recommended for uMMA:crea. Because of the wide distribution of uMMA:crea ratios, careful interpretation in intact male dogs is advised.
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spelling doaj-art-bade33c7e89b4b5aa08e9267cc4a25a82025-01-27T15:22:41ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762025-01-01391n/an/a10.1111/jvim.17250The effects of age and sex on reference intervals for cobalamin, homocysteine, and serum and urinary methylmalonic acid in healthy adult dogsAnna‐Lena Proksch0Sophia Schaefer1Vanessa Dreller2Judith Langenstein3Ralph Fingerhut4Natali Bauer5Andreas Moritz6Clinic for Small Animals, Internal Medicine, JLU Giessen, Frankfurter Strasse 114 Giessen 35392 GermanyClinic for Small Animals, Internal Medicine, JLU Giessen, Frankfurter Strasse 114 Giessen 35392 GermanyClinic for Small Animals, Internal Medicine, JLU Giessen, Frankfurter Strasse 114 Giessen 35392 GermanyAntech Lab Germany GmbH, Gubener Str. 39 Augsburg 86156 GermanySYNLAB MVZ Weiden GmbH, Zur Kesselschmiede 4 Weiden 92637 GermanyClinic for Small Animals, Internal Medicine, JLU Giessen, Frankfurter Strasse 114 Giessen 35392 GermanyClinic for Small Animals, Internal Medicine, JLU Giessen, Frankfurter Strasse 114 Giessen 35392 GermanyAbstract Background In dogs, data on reference intervals (RIs) for cobalamin, markers of metabolism (markersB12met), age and sex effects are limited. Hypothesis/Objectives Establish RI for serum cobalamin, homocysteine, and methylmalonic acid (sMMA) concentrations, urinary methylmalonic acid‐to‐creatinine ratio (uMMA:crea), and determine effects of sex and age. Methods Prospective study using healthy dogs (1‐10 years). Cobalamin and markersB12met were determined using chemiluminescence immunoassay (cobalamin) and liquid chromatography/tandem mass spectrometry (homocysteine, sMMA, uMMA:crea). In dogs with outlying data, changes in health, markersB12met, and onset of gastrointestinal signs were reevaluated after 9‐15 months. Results Twelve of 120 healthy dogs had abnormal uMMA:crea ratios. No other cobalamin analyte outliers were found. Outlying data re‐examination (odRE) was performed in 10/12 dogs. Chronic gastrointestinal signs occurred in 64% of odRE‐dogs, whereas 36% remained healthy. In total, 112 dogs (67 females, 45 males; median ages, 3.5 and 3.75 years, respectively) were included in RI analyses. Reference intervals were 178.5‐851 pmol/L (cobalamin), 5.8‐29.0 μmol/L (homocysteine), 45.3‐159.5 μg/L (sMMA), and ≤22.4 mg/g (uMMA:crea). Only age affected cobalamin concentrations (significant decrease). Compared by sex and neuter status, intact male dogs had significantly higher uMMA:crea ratios (median, 13.5; range, 1.9‐83.6 mg/g) than the other groups (median, 2.5; range, 0.7‐9.7 mg/g; P < .0001). Sex‐specific RI were ≤58.9 mg/g (intact male) vs ≤5.2 mg/g (females and neutered males). Conclusion and Clinical Importance Intact male dogs had significantly higher uMMA:crea ratios than the other groups. Thus, sex‐specific RI are recommended for uMMA:crea. Because of the wide distribution of uMMA:crea ratios, careful interpretation in intact male dogs is advised.https://doi.org/10.1111/jvim.17250B12 metabolismcanineserumsexurinevitamin B12
spellingShingle Anna‐Lena Proksch
Sophia Schaefer
Vanessa Dreller
Judith Langenstein
Ralph Fingerhut
Natali Bauer
Andreas Moritz
The effects of age and sex on reference intervals for cobalamin, homocysteine, and serum and urinary methylmalonic acid in healthy adult dogs
Journal of Veterinary Internal Medicine
B12 metabolism
canine
serum
sex
urine
vitamin B12
title The effects of age and sex on reference intervals for cobalamin, homocysteine, and serum and urinary methylmalonic acid in healthy adult dogs
title_full The effects of age and sex on reference intervals for cobalamin, homocysteine, and serum and urinary methylmalonic acid in healthy adult dogs
title_fullStr The effects of age and sex on reference intervals for cobalamin, homocysteine, and serum and urinary methylmalonic acid in healthy adult dogs
title_full_unstemmed The effects of age and sex on reference intervals for cobalamin, homocysteine, and serum and urinary methylmalonic acid in healthy adult dogs
title_short The effects of age and sex on reference intervals for cobalamin, homocysteine, and serum and urinary methylmalonic acid in healthy adult dogs
title_sort effects of age and sex on reference intervals for cobalamin homocysteine and serum and urinary methylmalonic acid in healthy adult dogs
topic B12 metabolism
canine
serum
sex
urine
vitamin B12
url https://doi.org/10.1111/jvim.17250
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