Three key attributes make the IDEXX SDMA Test an ideal test for assessing kidney function:

Biomarker for kidney function: Symmetric dimethylarginine (SDMA) is excreted by the kidneys. SDMA is an earlier indicator of changes in glomerular filtration rate (GFR) in dogs and cats.^1–3,14

Earlier than creatinine: SDMA increases as early as 25% loss of kidney function,² making SDMA more reliable in both acute or active kidney injury and chronic kidney disease.^1–3 Creatinine cannot identify kidney issues until almost 75% of kidney function is lost.^1,3

Specific for kidney function: SDMA is less impacted by extrarenal factors than creatinine, including body condition, advanced age, and disease state.^7,8

SDMA is also not affected by lean body mass, making it more reliable for assessing kidney function in animals with chronic kidney disease or other conditions that result in weight and muscle loss, such as hyperthyroidism.^7,8,14

SDMA is highly sensitive with studies supporting sensitivity as high as 100%.^3,15–17

Creatinine: SDMA is a reliable and sensitive indicator of kidney function in animals. SDMA increases earlier than creatinine in dogs and cats with both AKI and CKD,^1–3
and unlike creatinine, SDMA is not impacted by lean muscle mass.^7,8 SDMA increases on average with 40% loss of kidney function vs. creatinine,^1,3 which does not increase until up to 75% of kidney function is lost.^1,3 Creatinine is a breakdown product of muscle, and therefore, it is impacted by lean body mass, whereas SDMA is not.⁸

Blood urea nitrogen (BUN): BUN also increases later than SDMA, and it can be influenced by decreased production in liver disease and increases with high-protein meals or gastrointestinal bleeding vs. SDMA, with little to no extrarenal impacts.⁸

Urine specific gravity (USG): Loss of urine concentrating ability progresses with kidney disease and dysfunction, and it is apparent before metabolic wastes, such as BUN and creatinine, increase. This change occurs with approximately 67% loss of nephron function but is variable.¹⁸ SDMA may increase in patients with early kidney disease that can still concentrate their urine. Natural fluctuations in USG are common in healthy animals and are influenced by how much the animal drinks before urine collection. Poor urine concentration is not specific to the kidney, and it can be influenced by other diseases (e.g., diabetes, liver disease, and Cushing’s disease), whereas SDMA is influenced by changes in GFR.¹⁵ Finding a persistently increased IDEXX SDMA concentration and inappropriately concentrated urine suggests kidney disease is probable, and immediate action should be taken.⁹

Urine protein:creatinine (UPC) ratio: The UPC ratio is a urine test. It is used to fully quantify protein detected in the urine once transient proteinuria, urinary tract infection, inflammation, or significant hematuria have been ruled out. The UPC ratio may detect kidney disease earlier than creatinine if the primary target of the disease is the glomerulus and in some cases of tubulointerstitial disease. However, it is common for the UPC ratio to remain normal in animals with CKD, especially in early stages when SDMA may be increased. Persistent proteinuria that results in UPC ratios greater than 0.4 in cats and 0.5 in dogs, where prerenal and postrenal proteinuria have been ruled out, is consistent with glomerular or tubulointerstitial CKD, whereas UPC ratios greater than 2.0 are strongly suggestive of glomerular disease. In animals with proteinuria, the UPC ratio should be used to monitor progression and response to treatment.¹⁹

SDMA is excreted from the kidneys; therefore, as kidney function or GFR decreases, SDMA increases. Studies have shown a very strong correlation between SDMA and GFR in dogs and cats.^1,3 A benefit of using SDMA along with creatinine, which typically increases above the reference interval when there is up to a 75% reduction in GFR,^1,3 is that SDMA increases when there is, on average, a 40% decrease in GFR.^1,3 In some cases, SDMA increases earlier when there is 25% reduction of GFR, representing 25% loss of kidney function.^2,3

Performing a GFR clearance test is the gold standard for measuring GFR and assessing kidney function. However, performing a GFR clearance test is expensive, cumbersome, and not routinely done in practice.

SDMA correlates well with GFR, increasing when there is, on average, a 40% loss of kidney function,^1,3 and as little as 25% loss.² Reduced urine concentrating ability typically appears when there is, on average, a 67% loss of GFR, but this is variable.²⁰ Cats with experimentally induced kidney disease retained concentrating ability despite loss of 75% of renal mass.²¹ Given the lack of correlation between GFR and USG, a linear relationship between SDMA and USG could not be expected.

SDMA will, however, typically increase before isosthenuria associated with renal dysfunction develops. In many cases of early CKD, where SDMA is increased but creatinine is normal, the dog or cat will have an inappropriate USG (i.e., less than 1.030 for dogs or less than 1.035 for cats). However, in more than 25% of dogs and cats with an increased SDMA, significant urine concentrating ability will still remain because their GFR is only mildly decreased, or because of the variable timing of loss of concentrating ability. In patients with persistently increased SDMA where dehydration has been excluded, kidney disease is probable and should be further investigated, even if appropriate urine concentrating ability is noted.⁴

Untreated hyperthyroid cats have increased glomerular filtration rate (GFR) and loss of muscle mass secondary to their hyperthyroidism, which can hide underlying CKD. The IDEXX SDMA Test is a more reliable indicator of kidney function than creatinine in hyperthyroidism because, unlike creatinine, the IDEXX SDMA Test is not affected by lean body mass and appears to be only slightly blunted by hyperfiltration.^22,23