Date Published: October 15, 2018
Publisher: Public Library of Science
Author(s): Rie Ernst, Jennifer Ogeer, Donald McCrann, Julie Cross, Marilyn Strong-Townsend, Hanne Friis, Michael Coyne, Celeste Clements, Corie Drake, Rachel Murphy, Douglas H. Thamm.
Kidney disease is common in companion animals, and traditionally diagnosed with serum creatinine concentration (sCr), blood urea nitrogen, and abnormal urinalysis findings. Symmetric dimethylarginine (SDMA) is a novel kidney biomarker that reflects glomerular filtration rate, increasing earlier than sCr with acute kidney injury and chronic kidney disease. This prospective study compared accuracy and precision of two commercial SDMA assays, the IDEXX SDMA Test and the DLD SDMA ELISA, relative to the established reference method, liquid chromatography/mass spectrometry (LC-MS). Thirty canine and 30 feline pooled serum samples were used to evaluate accuracy compared to LC-MS. Pooled canine samples with a low SDMA concentration and pooled feline samples with a high SDMA concentration were used to evaluate precision. Using a best fit linear model, the IDEXX SDMA Test resulted in a slope of 1.06 and an intercept of 0.34, with R2 = 0.99, and the DLD SDMA ELISA resulted in a slope of 0.37 and an intercept of 11.33, with R2 = 0.27, when compared to LC-MS. Estimated bias over a clinically relevant range for SDMA (10–45 μg/dL) was 1–2 μg/dL for the IDEXX SDMA Test, while DLD SDMA ELISA showed considerable bias, 5–8 μg/dL. Day-to-day precision analysis of the low SDMA concentration samples showed 7.7% total coefficient of variation (CV) for the IDEXX SDMA Test and 31.1% for the DLD SDMA ELISA. For the high SDMA concentration samples, total CV was 2.3% for the IDEXX SDMA Test and 28.2% for the DLD SDMA ELISA. In this study the IDEXX SDMA Test was more accurate and more precise in macroscopically normal serum than the DLD SDMA ELISA when compared to the reference method of LC-MS. The IDEXX SDMA Test is more suitable for clinical use in the diagnosis and monitoring of kidney disease in dogs and cats.
Kidney disease is common in small animals, with chronic kidney disease (CKD) recognized as an important cause of morbidity and mortality in cats [1, 2] and dogs . Early diagnosis and nutritional management of kidney disease are recommended to slow progression and improve survival time of cats [2, 4, 5] and dogs  diagnosed with CKD. Early decreases in glomerular filtration rate (GFR) are not readily recognized by the commonly used diagnostic tests, including sCr and blood urea nitrogen (BUN) [7–9]. Symmetric dimethylarginine (SDMA) is a methylated form of arginine found within all nucleated cells that is released into circulation after proteolysis, then excreted through the kidneys, and correlates well with GFR in people , dogs [3,11], and cats [12–13]. SDMA has been shown to increase earlier than sCr in cats  and dogs with CKD  and studies have demonstrated that SDMA increases when there is 25%- 40% decrease in GFR [3,11,13]. SDMA is also more specific than sCr, being less impacted by extrarenal factors including body condition and advanced age [14–17]. Since SDMA is not affected by lean body mass [14,15] it is potentially more reliable for assessing kidney function in animals with conditions that result in muscle loss, such as feline hyperthyroidism or advanced CKD. In 2015 IRIS amended the CKD guidelines to incorporate SDMA, along with sCr, for the diagnosis and treatment of CKD in dogs and cats, noting that SDMA may be a more sensitive indicator of kidney function than sCr , and that SDMA may be used as an adjunct to sCr to guide treatment for patients with low body-condition scores, in which sCr may underestimate the degree of renal dysfunction .
The diagnosis of kidney disease is multifaceted, including assessment of patient signalment, history, clinical signs, physical examination findings, and results of diagnostic testing, including hematology, biochemistry, urinalysis, medical imaging and ancillary evaluations such as blood pressure measurement. Veterinary clinicians utilize laboratory assessment of sCr and BUN to diagnose kidney disease, analytes which have been shown to be insensitive, late markers of kidney dysfunction [7–9, 22] and non-specific, namely, influenced by extrarenal factors . SDMA is a more sensitive and earlier indicator of kidney function that can indicate progressive kidney function loss before other parameters and is less influenced by extra-renal factors [3, 11, 13–15]. Accurate and precise SDMA measurements are needed to optimize patient diagnosis and management based on standardized IRIS CKD staging and individual patient concerns. When compared to SDMA measured by LC-MS on the same individual patient samples, IDEXX SDMA Test results showed strong agreement. In this study SDMA concentrations measured with the IDEXX SDMA Test were substantially more accurate and more precise in macroscopically normal serum than those measured with the DLD SDMA ELISA when compared to the reference method of LC-MS.
In this study SDMA concentrations measured with the IDEXX SDMA Test were more accurate and more precise in macroscopically normal serum than those measured with the DLD SDMA ELISA when compared to the reference method of LC-MS. The IDEXX SDMA Test is more suitable for clinical use in the diagnosis and monitoring of kidney disease in dogs and cats.