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 (markersBmet), 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&#x2009;years). Cobalamin and markersBmet were determined using chemiluminescence immunoassay (cobalamin) and liquid chromatography/tandem mass spectrometry (homocysteine, sMMA, uMMA:crea). In dogs with outlying data, changes in health, markersBmet, and onset of gastrointestinal signs were reevaluated after 9-15&#x2009;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&#x2009;years, respectively) were included in RI analyses. Reference intervals were 178.5-851&#x2009;pmol/L (cobalamin), 5.8-29.0&#x2009;&#x3bc;mol/L (homocysteine), 45.3-159.5&#x2009;&#x3bc;g/L (sMMA), and &#x2264;22.4&#x2009;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&#x2009;mg/g) than the other groups (median, 2.5; range, 0.7-9.7&#x2009;mg/g; P&#x2009;<&#x2009;.0001). Sex-specific RI were &#x2264;58.9&#x2009;mg/g (intact male) vs &#x2264;5.2&#x2009;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.