SDMA: Satisfy your need for speed (in diagnosing CKD)

Getty ImagesIn her IDEXX-sponsored presentation, “SDMA in practice: Impact on diagnosis, staging, and management of CKD,” at the 2016 American College of Veterinary Internal Medicine (ACVIM) Forum, IDEXX Director of Medical Affairs Jane Robertson, DVM, DACVIM, discussed how the symmetric dimethylarginine (SDMA) biomarker can be used to diagnose chronic kidney disease (CKD) in cats and dogs far sooner than with traditional methods.   

Robertson cited studies demonstrating that in dogs with renal disease, SDMA elevations can be seen approximately 9.8 months before creatinine becomes elevated.1 In cats, the average is about 17 months.2 This means increases in SDMA concentrations can be identified when only 25% of kidney function has been lost (40% average),2 as opposed to a loss of 65% to 75% by the time azotemia can be noted.

Robertson also explained that creatinine may lose sensitivity as an indicator of CKD in elderly patients with diminished muscle mass, but studies indicate that SDMA is not affected by muscle loss.3,4

Can creatinine be elevated before SDMA?

In short, yes. While uncommon, Robertson said that in 1.3 million canine samples submitted to IDEXX, 1.6% of cases showed elevated creatinine concentrations before elevations in SDMA concentrations. In cats, this condition has been noted in 1.1% of over 600,000 samples. While it is unclear why the creatinine concentration would be elevated before the SDMA concentration, Robertson offered three possible reasons:

It is normal for glomerular filtration rates and SDMA to fluctuate by about 15% on a daily basis.

Patients that are highly muscled may have abnormally high creatinine concentrations.

Drug interactions (e.g. cephalosporins) may lead to discordant results.

Using SDMA within the International Renal Interest Society (IRIS) guidelines

Once the patient's renal function measurements have stabilized and IRIS staging and substaging can be assessed, SDMA can be used to help evaluate trends in individual animals. Robertson emphasized that while the current IRIS guidelines do not currently specify SDMA cut-off values for each stage of CKD, there are some general values that can be used to assess progression.

For example, IRIS stage 2 CKD patients with an SDMA concentration greater than 25 µg/dl would benefit from being treated as though they are stage 3. Similarly, treatment for stage 4 should be considered in IRIS stage 3 CKD patients with an SDMA concentration greater than 45 µg/dl.

Investigate, manage, and monitor approach

Robertson discussed how to apply an investigate, manage and monitor approach to clinical scenarios in order to demonstrate how SDMA may be used to develop a plan for treatment and monitoring.

For example, in a patient with an elevated SDMA concentration, low urine specific gravity, no clinical signs, normal creatinine concentration and normal physical examination results, the following approach could be applied:

Investigate:

Check the urine protein-to-creatinine ratio.

Perform a urine culture.

Assess blood pressure.

Use diagnostic imaging.

Screen for infectious diseases (depending on geographic location).

Manage:

Avoid drugs that can negatively affect the kidneys (e.g. NSAIDs).

Use appropriate anesthetic protocols and intravenous fluids to maintain renal perfusion during procedures.

Consider implementing a renal-specific diet.

Offer multiple water sources to encourage increased water intake.

Treat proteinuria and hypertension as needed.

Monitor:

Recheck the patient in two weeks to determine progression.

Other monitoring will depend on diagnostic findings and changes in clinical signs-particularly anything that could affect hydration (e.g. vomiting, diarrhea).

Robertson noted that there is still much to learn about how SDMA is affected by various medical conditions, but studies are already underway to assess the interaction between feline hyperthyroidism and SDMA.

References

Yerramilli M, Yerramilli M, Obare E, et al. Symmetric dimethylarginine (SDMA) increases earlier than serum creatinine in dogs with chronic kidney disease (CKD) (abst). J Vet Intern Med 2014;28(3):1084-1085.

Hall JA, Yerramilli M, Obare E, et al. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease. J Vet Intern Med 2014;28(6):1676-1683.

Hall JA, Yerramilli M, Obare E, et al. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in healthy geriatric cats fed reduced protein foods enriched with fish oil, L-carnitine, and medium-chain triglycerides. Vet J 2014;202(3):588-596.

Hall JA, Yerramilli M, Obare E, et al. Relationship between lean body mass and serum renal biomarkers in healthy dogs. J Vet Intern Med 2015;29(3):808-814.