When Creatinine Can Mislead: The Role of SDMA in Canine CKD

Early identification of chronic kidney disease (CKD) can be challenging because renal dysfunction may develop before obvious clinical signs appear. Serum creatinine (sCr) has traditionally been used to evaluate glomerular filtration rate (GFR), but its interpretation is influenced by muscle mass. Creatinine values increase with substantial loss of functional nephrons, while reduced muscle mass can result in lower sCr concentrations and make renal function appear better than it actually is¹. 

This becomes particularly important when evaluating older dogs or patients with poor body condition, cachexia, or sarcopenia. In these patients, interpreting creatinine alongside other renal biomarkers can provide a more complete picture of renal function. 

Where SDMA Fits In 

Symmetric dimethylarginine (SDMA) is an endogenous biomarker of GFR that is predominantly eliminated through the kidneys. In dogs, SDMA increases when approximately 40% of functional nephrons have been lost and may therefore provide information during pre-azotemic stages^2,3. 

Its clinical relevance was evaluated in a prospective assessment of 388 dogs with different risk factors for developing CKD. Clinical history, physical examination, body condition score (BCS), complete blood count, biochemical profile including sCr and SDMA, urinalysis, urine protein/creatinine ratio (UPC), and systemic blood pressure were assessed during the initial evaluation. 

Among the 86 dogs classified in G1, representing non-azotemic dogs with SDMA values of 15–17 mg/dL, 25.6% had altered GFR identified by SDMA, while 59.3% had proteinuria. A further 15.1% had abnormalities in both biomarkers. 

These findings support considering SDMA and UPC alongside conventional renal parameters when CKD is suspected before azotemia develops. 

Why Body Condition Matters¹ 

Body condition can significantly influence the interpretation of creatinine. In the evaluated population, 23.0% of azotemic dogs had a BCS below 5/9. Because creatinine is closely associated with skeletal muscle, reduced muscle mass can result in lower sCr concentrations and potentially overestimate renal function. 

Low BCS was more frequently observed in dogs classified in G2, G3, and G4, corresponding to more advanced disease categories. Cachexia and sarcopenia were associated with these lower body condition scores. In such patients, SDMA may provide useful complementary information because it is not affected by muscle mass in the same manner as creatinine. 

SDMA and Creatinine: Related but Not Interchangeable¹ 

The four groups of dogs considered potentially affected by chronic kidney disease (pCKD) were G1, G2, G3, and G4. When these groups were evaluated together, SDMA and sCr showed a moderate correlation (r=0.69, p<0.001). Both biomarkers increased as disease severity increased. 

However, the two biomarkers did not always show corresponding values. In 19.2% of azotemic cases, SDMA remained within the reference range despite increased sCr. This reinforces the importance of interpreting SDMA alongside clinical history, physical examination, laboratory findings, and follow-up rather than using it as an isolated diagnostic measure. 

UPC also provided complementary information. Proteinuria was observed frequently in the pCKD groups and may occur before increases in SDMA or sCr, making UPC relevant to the identification of renal disease during earlier stages. 

Practical Clinical Approach 

For a dog with recognized risk factors for CKD, the initial renal assessment should bring multiple parameters together: 

• sCr and SDMA for assessment of renal function. 

• UPC to identify proteinuria. 

• Urine specific gravity (USG) as part of the urinalysis. 

• Phosphorus and systemic blood pressure to identify additional abnormalities associated with renal disease. 

• BCS to help interpret sCr, particularly in dogs with reduced muscle mass. 

The findings from this 388-dog population support using SDMA as a complementary biomarker rather than a replacement for creatinine or other renal assessments. Its value is particularly relevant when renal dysfunction is suspected before azotemia or when reduced muscle mass makes creatinine more difficult to interpret. However, SDMA should not be used as the sole biomarker for evaluating renal function in dogs. 

References 

1. Pérez-Sánchez A, Perini-Perera S, Del-Angel-Caraza J, Quijano-Hernández I. Correlation of renal function biomarkers in the first diagnostic approach to canine chronic kidney disease. Journal MVZ Córdoba. 2023 Jan;28(1):e2782. https://www.academia.edu/download/119150340/mvz_i_v28n1_2782.pdf 

2. Kielstein JT, Salpeter SR, Bode-Boeger SM, Cooke JP, Fliser D. Symmetric dimethylarginine (SDMA) as endogenous marker of renal function—a meta-analysis. Nephrology Dialysis Transplantation. 2006 Sep 1;21(9):2446-51. https://academic.oup.com/ndt/article-pdf/21/9/2446/7624927/gfl292.pdf 

3. McKenna M, Pelligand L, Elliott J, Cotter D, Jepson R. Relationship between serum iohexol clearance, serum SDMA concentration, and serum creatinine concentration in non-azotemic dogs. Journal of Veterinary Internal Medicine. 2020 Jan;34(1):186-94. https://academic.oup.com/jvim/article-pdf/34/1/186/66660426/jvim15659.pdf