Imagine this clinical scenario: you are performing bloodwork on a cat to screen for renal change as part of a routine senior health check. Your results have discordant symmetric dimethylarginine (SDMA) and serum creatinine (sCr) values that would place the cat in different stages according to the International Renal Interest Society (IRIS) guidelines and you would like to know which result better correlates to kidney function. You decide to consult the evidence to find whether SDMA is superior to sCr as an indicator of glomerular filtration rate (GFR) in cats.
The evidence
Four papers studied the correlation between SDMA and GFR, and sCr and GFR. Three of the studies were retrospective diagnostic test studies (Hall et al., 2014a; Braff et al., 2014; Brans et al., 2021), and one was a cross-sectional study from a randomised control trial (Hall et al., 2014b).
Brans et al. (2021) studied 49 adult cats: 17 with chronic kidney disease (CKD), 15 with diabetes mellitus and 17 healthy control cats. sCr data, which had been measured using a plasma exogenous iohexol clearance test, was retrieved from the patients’ medical records. SDMA was measured from residual clearance test plasma samples that had been stored from three to eight years prior.
Braff et al. (2014) studied 10 cats: four with sCr concentrations above 2mg/dl and six with sCr concentrations below this level. The sCr values for each patient were gathered as part of a previous study. SDMA was calculated using high-performance liquid chromatography (HPLC) using frozen samples from a previous study. GFR was measured using data from a previous study and was determined by plasma iohexol clearance.
Hall et al. (2014a) studied 42 cats with an age range of 1 to 19 years. Of these patients, 21 cats had CKD and 21 presented as healthy geriatric cats (over 10 years old). sCr data was measured using retrospective data and SDMA was measured using liquid chromatography-mass spectroscopy.
Hall et al. (2014b) studied 32 cats that were fed one of three diets: a control diet or one of two experimental diets. sCr was measured using enzymatic colorimetry and SDMA was measured using liquid chromatography-mass spectroscopy. GFR was measured by iohexol clearance.
Limitations of the evidence
The overall strength of the evidence is moderate due to various limitations. A key limitation that impacted the comparability of these studies is the variability of the reference intervals applied for the measurement of sCr and SDMA. Brans et al. (2021) acknowledged this limitation in their study, in which they looked at two different threshold values for sCR. By doing so, they recognised that a higher upper reference limit resulted in more false negative results.
Three of the papers (Brans et al., 2021; Braff et al., 2014; Hall et al., 2014a) also tested samples for SDMA that had been stored for varying periods of time. This presents potential issues with the reliability of outcomes, as the long-term stability of SDMA has not been determined. Hall et al. (2014a) studied samples that had been frozen with no information on the length of time they had been stored. No data on the stability of SDMA in frozen samples from cats is available.
Some of the cats categorised as ‘healthy’ in these studies may have been categorised as having CKD by following IRIS guidelines
Two studies (Hall et al., 2014a; Brans et al., 2021) were limited by a lack of randomisation in their case selection. Both studies by Hall et al. (2014a, 2014b) used an upper reference range for creatinine that was higher than that used for IRIS staging. Therefore, some of the cats categorised as “healthy” in these studies may have been categorised as having CKD by following IRIS guidelines.
Brans et al. (2021) had the additional limitation that only 17 of the 49 cats studied were displaying symptoms of CKD.
Braff et al. (2014) had the additional limitations of selection bias and small sample size. Hall et al. (2014a) had no further limitations, while Hall et al. (2014b) had one further limitation: this study did not specifically look at cats with CKD, lowering its relevance to this research question.
It must also be taken into account that creatinine is affected by more non-renal factors than SDMA, such as lean body mass, age and diet. However, SDMA and creatinine can also be affected by breed and biological variability and pre-renal causes of reduced GFR such as dehydration (Sargent et al., 2021).
Summary of findings
Three of the studies (Braff et al., 2014; Hall et al., 2014a; Brans et al., 2021) found an equal correlation between SDMA and GFR and creatinine and GFR, while one study (Hall et al., 2014b) showed a stronger correlation between SDMA and GFR.
Brans et al. (2021) found that there was an equally significant moderate correlation between plasma SDMA and GFR, between sCr and GFR, and between SDMA and sCr. Braff et al. (2014) found that there was a significant linear relationship between both SDMA and GFR and creatinine and GFR. Therefore, they determined that SDMA and creatinine performed equally in detecting changes in GFR. Hall et al. (2014a) found that there was a positive linear relationship between SDMA and sCr, and that both were significantly correlated to GFR.
Hall et al. (2014b), on the other hand, found a stronger correlation between SDMA and GFR than creatinine and GFR.
Conclusion
There is moderate evidence to suggest that SDMA is not superior to creatinine for assessment of GFR
While there is some conflicting evidence and all of the papers studied had limitations, there is moderate evidence to suggest that SDMA is not superior to creatinine for assessment of GFR. Therefore, clinicians should be aware of any potential non-renal factors that can affect this measurement when interpreting discordant results in practice. Further studies with more robust study design and fewer limitations are required to improve the strength of evidence.
The full Knowledge Summary can be read in RCVS Knowledge’s open access journal Veterinary Evidence. |
Disclaimer
The application of evidence into practice should take into account multiple factors, not limited to individual clinical expertise; patient’s circumstances and owner’s values; country, location or clinic where you work; the individual case in front of you; and the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.