When Creatinine May Not Tell the Full Story in Feline Acute Kidney Injury

Serum creatinine is routinely used with changes in urine output to diagnose and grade Acute Kidney Injury (AKI). However, its limitations become important when renal injury is developing. Creatinine is an insensitive marker of decreased Glomerular Filtration Rate (GFR), particularly in AKI, because its relationship with GFR is nonlinear^[1]. It may also be influenced by diet, hydration status, and muscle mass^[1],[2]. 

Timing is another concern. Serum creatinine typically increases 48–72 hours after renal injury^[3], and hypercreatinemia may not become evident until approximately 75% of renal function has been lost^[1],[4]. This delay can make recognition of declining renal function difficult when AKI is developing. 

Why Consider Symmetric Dimethylarginine? 

Symmetric Dimethylarginine (SDMA) is a by-product of intranuclear protein methylation and is primarily excreted through renal filtration.Unlike creatinine, SDMA concentration is less influenced by muscle mass^[1],[5]. 

SDMA can increase with a smaller reduction in GFR. Increases above the reference interval have been reported with an average GFR reduction of 40% in cats and dogs and 24% in cats alone^[1]. This makes SDMA relevant when evaluating biomarkers that may reflect reduced filtration before creatinine becomes markedly abnormal. 

What Was Found in Cats With AKI?^[1] 

In a retrospective evaluation of cats with azotemic AKI, serum SDMA concentrations were compared among cats with novel AKI, Acute-on-Chronic Acute Kidney Injury (AoC-AKI), Chronic Kidney Disease (CKD), and control cats. 

Serum SDMA was significantly higher in cats with renal azotemia than in control cats. Among cats with novel AKI, the median SDMA concentration was 36 μg/dL (range 9–170), compared with 11 μg/dL (range 8–21) in control cats. The median concentration was 33 μg/dL (range 20–75) in cats with AoC-AKI and 19 μg/dL (range 12–69) in cats with CKD. 

The analysis also showed a relationship between SDMA concentration and AKI severity. Cats with more severe AKI, based on higher International Renal Interest Society (IRIS) AKI grades, had higher serum SDMA concentrations. A significant difference was identified between cats with IRIS grade IV/V AKI and those with grade II AKI. 

Within the evaluated population, therefore, higher SDMA concentrations were associated with established azotemic AKI and greater AKI severity. 

How Does SDMA Relate to Creatinine?^[1] 

Serum SDMA showed a strong positive correlation with serum creatinine in cats with novel AKI. A strong positive correlation was also identified when control, CKD, AoC-AKI and novel AKI cats were considered together. 

However, this correlation does not mean that either biomarker directly measures GFR during AKI. Serum creatinine and SDMA are not accurate reflections of GFR when steady-state equilibrium is absent. 

What About Early AKI? 

The findings raise an important question: could SDMA identify renal dysfunction before creatinine becomes elevated? 

The cats evaluated had established azotemic AKI, so this question was not answered directly. However, many cats with AKI had no previous history of renal dysfunction. This provides a basis for prospective evaluation of SDMA in nonazotemic AKI and IRIS grade I AKI, where creatinine may not yet show a marked increase. 

Further prospective evaluation is needed before SDMA can be considered an established early biomarker of feline AKI. 

Clinical Bottom Line 

SDMA can provide additional information when assessing renal dysfunction in cats with established azotemic AKI. In the evaluated population, SDMA concentrations were higher in cats with AKI and increased with greater AKI severity. 

Its potential role in detecting early, nonazotemic AKI remains to be established. At present, SDMA should complement, rather than replace, clinical assessment and conventional markers used in evaluating feline renal dysfunction.

References:

1. Loane SC, Thomson JM, Williams TL, McCallum KE. Evaluation of symmetric dimethylarginine in cats with acute kidney injury and chronic kidney disease. Journal of veterinary internal medicine. 2022 Sep;36(5):1669-76. https://academic.oup.com/jvim/article-pdf/36/5/1669/66665093/jvim16497.pdf
2. Hall JA, Yerramilli MV, Obare E, Yerramilli M, Jewell DE. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease. Journal of veterinary internal medicine. 2014 Nov;28(6):1676-83. https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.12445
3. Slocum JL, Heung M, Pennathur S. Marking renal injury: can we move beyond serum creatinine?. Translational Research. 2012 Apr 1;159(4):277-89. https://pmc.ncbi.nlm.nih.gov/articles/PMC3308350/pdf/nihms360231.pdf
4. Von Hendy-Willson VE, Pressler BM. An overview of glomerular filtration rate testing in dogs and cats. The Veterinary Journal. 2011 May 1;188(2):156-65. https://pmc.ncbi.nlm.nih.gov/articles/PMC2980797/pdf/nihms206318.pdf
5. Hall JA, Yerramilli M, Obare E, Yerramilli M, Melendez LD, Jewell DE. Relationship between lean body mass and serum renal biomarkers in healthy dogs. Journal of Veterinary Internal Medicine. 2015 May;29(3):808-14. https://academic.oup.com/jvim/article-pdf/29/3/808/66688010/jvim12607.pdf