SDMA (symmetric dimethylarginine) is the amino acid, arginine, that contains two methyl groups (dimethyl) in a symmetrical orientation. SDMA is considered a sensitive and early marker (more sensitive than serum creatinine) of declining GFR in dogs and cats (Hokamp and Nabity 2016 review).
SDMA is produced by all nucleated cells at a constant rate, with highest concentrations in the brain, and is excreted primarily by the kidneys, with some evidence of liver uptake in humans. It does not appear to be reabsorbed in renal tubules or influenced by many non-renal factors, other than diet (Hokamp and Nabity 2016 review).
SDMA testing is currently not offered by Cornell University. The gold standard method is high performance liquid chromatography-mass spectrophotometry, however an immunologic-based assay has been developed and is in current use (Hokamp and Nabity 2016 review).
Units of measurement
SDMA is measured in μg/dL (conventional units) or μmol/L (SI units).
Serum, heparinized plasma
Stable in canine and feline samples for one week at room temperature, 14 days at 4ºC and over a year frozen at -20 or -80ºC (Hokamp and Nabity 2016 review).
Studies in dogs and cats to date show a good correlation (around 70-80%) between SDMA and GFR (as measured by inulin or iohexol clearance in some studies) and it is currently thought to be a more sensitive marker of GFR than creatinine, although few studies have been performed to date (Hokamp and Nabity 2016 review). A study of 20 clinically healthy dogs in New Zealand, in which serial measurement of SDMA were performed on 9 different occasions, showed that the mean SDMA concentration was above the reference interval in 4 dogs, with another 11 dogs having individual values that fell above the reference interval. Three of the dogs with mean SDMA higher than upper limit of the reference interval of 14 ug/dL also had high creatinine concentrations, suggesting they did have subclinical renal disease. This was not confirmed by GFR testing. It is difficult to believe that the other 11 dogs with high individual values all have renal disease and the authors posited that the reference interval needed adjusting. In the same study, the authors demonstrated a weak correlation of 0.49 (per figure, in text 0.7) between SMDA and creatinine concentrations (measured using the enzymatic method) with a negative proportional bias between the two assays on a difference or Bland-Altman plot (creatinine increased in relation to values as both concentrations increased). From this study, the authors determined that the SDMA assay had moderate individuality (index of individuality of 0.87) and that population reference intervals may be appropriate for use, whereas creatinine had high individuality (index of individuality <0.6 at 0.28), indicating that critical differences should be used for this particular creatinine assay (the critical difference was 0.01 mg/dL, which was below assay variability!). The analytical variation of the two assays was 9.5 and 2% for SDMA and creatinine, respectively, although it was unclear how this variation was calculated (Kopke et al 2018).
Increased serum/plasma cystatin C concentrations
A recommended upper limit of a reference interval for dogs and cats is 14 μg/dL (Hokamp and Nabity 2016 review).
- Pathophysiologic: As indicated above, measurement of SDMA is currently being used as a sensitive and early marker of decreased GFR in dogs and cats (Hokamp and Nabity 2016 review).
- Azotemia post treatment for hyperthyroidism: In a study of 242 hyperthyroid non-azotemic cats, 42 cats became azotemic after radioactive iodine therapy, with azotemia being defined by high serum creatinine concentrations (>2.0 mg/d). The SDMA concentration was high in 19 of the 42 cats with creatinine within reference intervals before radioactive iodine treatment but in three of these cats, the SDMA normalized after treatment. The cause of the high SDMA in these cats is not known, but this suggests that high SDMA concentrations do not always mean renal dysfunction or that the renal dysfunction was transient. This study did show that SDMA was more sensitive than creatinine for picking up changes in GFR in cats with hyperthyroidism, although a USG <1.035, and both SDMA and creatinine concentrations independently predicted renal azotemia post radioactive iodine treatment in this cohort of cats. Many cats with hyperthyroidism had low SDMA (<10 ug/dL), which was attributed to the increased GFR in this syndrome (Peterson et al 2018).
- Hypothyroidism: In the above study o, cats that developed azotemia after radioactive iodine therapy were more likely to be hypothyroid, suggesting hypothyroidism may cause decreased GFR and increased SDMA concentrations. However hypothyroidism is quite rare in cats (except for those treated with radioactive iodine) so it would be difficult to test this theory (Peterson et al).