Heresy question- How valid is SDMA in a breed specific situation

RE: Heresy question- How valid is SDMA in a breed specific situation

Martin Atkinson — Tue, 28 Mar 2017 13:55:33 GMT

[quote user="Jennifer Ogeer"]My colleague, Graham, and I would like to thank you for asking us to stop by to comment about SDMA.[/quote]Maybe time to eat my hat, it certainly sounds convincing but for the average pet what is it's value? Do we reserve it for when there are clinical signs of CKD i.e. PD/PU or add it in to routine older pet profiles when there may already be a cost constraint. And if there is a 'positive' SDMA test, if the animal is asymptomatic, how does this reflect on its care given we're likely already recommending lowered protein/phosphate diets in these animals?

And if it's not inappropriate, any comments on my dismissal of the value of SNAP NT-proBNP?

RE: Heresy question- How valid is SDMA in a breed specific situation

Jennifer Ogeer — Tue, 28 Mar 2017 00:24:50 GMT

Hi Aine and Rob,

My colleague, Graham, and I would like to thank you for asking us to stop by to comment about SDMA in different dog breeds and the impact of lipaemic samples on analysis. Thank you for your patience.

Numerous studies have shown that the IDEXX SDMA test is a more reliable marker of GFR than creatinine in dogs and cats, since it increases earlier than creatinine and is not affected by lean body mass. (1-5) The effects of sample quality have also been extensively studied: lipaemia and icterus do not affect SDMA results, nor does mild to moderate hemolysis. IDEXX SDMA Test results may be depressed in markedly hemolyzed specimens, however. (1,6)

IDEXX has reported millions of paired SDMA and creatinine results to customers, based on reference intervals established by a true reference interval study of clinically healthy dogs and cats following CLSI guidelines (7). Since measurement of all analytes are affected by the methodology used, including the type of chemistry analyzer and the reagents and calibrators, a universal reference interval for any given analyte across all methodologies is not possible.

Our Medical Data Analytics team is actively studying the “big data” to investigate how creatinine and SDMA vary across dog and cat breeds. Creatinine concentrations do vary quite significantly according to dog breed size. With similar statistical analytical methods the IDEXX SDMA™ Test displays significantly less variation. A greyhound specific study is underway There is a more moderate impact of breeds in cats and SDMA is barely impacted by cat breed. Publications of this data are planned, and we will be happy to share as results are finalized (8).

We have also been asked if creatinine would be just as good as SDMA if the upper end of the creatinine reference interval was just lowered. Hall’s published study of cats with CKD proved not. The sensitivity of SDMA was 100% and the specificity was 91% when compared to the gold standard of GFR. The sensitivity of creatinine, however, was only 17% when using the reference interval for their laboratory. When the IRIS CKD Stage 1 cut off for creatinine of 1.6 mg/dL (140 µmol/l) (9) was used instead, the sensitivity still only increased to 50%. SDMA is more reliable, as it is better correlated with GFR and is more sensitive than creatinine. (2)

Aine, your clinical concerns about this young Boxer patient are understandable. I would hate to see you abruptly withdraw a medication that is giving him a better quality of life without weighing carefully the potential risks of continuing a drug that may be affecting his GFR . From your post I can’t really tell the duration of the increase in SDMA, nor do I did not see any urinalysis results. The increase in SDMA may still be significant for this patient even though it’s only mild. We do suggest that SDMA be interpreted first along with other kidney function tests and other clinical information.

Additional consultation with your local specialist about completing the kidney workup seems warranted, if not already performed. If no additional evidence of kidney disease is determined from imaging studies and testing for infectious causes, and no confounding factors of hypertension and proteinuria are identified, then it may be reasonable to just follow his kidney function tests including SDMA ,creatinine and complete urinalysis more closely over time (weeks to months) for any suggestions of further GFR changes, as you might with patients with Stage 1 or early stage 2 CKD.

With warm regards,

Jennifer Ogeer,

Medical Affairs Marketing Manager

IDEXX Laboratories Inc.

References:

Nabity MB, Lees GE, Boggess M, et al. Symmetric dimethylarginine assay validation, stability, and evaluation as a marker for early detection of chronic kidney disease in dogs. J Vet Intern Med. 2015;29(4):1036–1044.
Hall JA, Yerramilli M, 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. J Vet Intern Med. 2014;28(6):1676–1683.
Hall JA, Yerramilli M, Obare E, Yerramilli M, Almes K, Jewell DE. Serum concentrations of symmetric dimethylarginine and creatinine in dogs with naturally occurring chronic kidney disease. J Vet Intern Med. 2016;30(3):794–802.
Hall JA, Yerramilli M, Obare E, Yerramilli M, Yu S, Jewell DE. 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, Yerramilli M, Melendez LD, Jewell DE. Relationship between lean body mass and serum renal biomarkers in healthy dogs. J Vet Intern Med. 2015;29(3):808–814.
Patch D, Obare E, Xie H, et al. High throughput immunoassay that correlates to gold standard liquid chromatography mass spectrometry (LCMS)assay for the chronic kidney disease (CKD) marker symmetric dimethylarginine (SDMA) [ACVIM Abstract NU19].J Vet Intern Med. 2015;29(4):1216.
Rentko V, Nabity M, Yerramilli M, et al. Determination of serum symmetric dimethylarginine reference limit in clinically healthy dogs [ACVIM Abstract P7]. J Vet Intern Med. 2013;27 (3): 750.
IDEXX data on file.
International Renal Interest Society. 2015 IRIS CKD Staging Guidelines. www.iris-kidney.com/pdf/staging-of-ckd.pdf. Accessed September 30, 2016.

RE: Heresy question- How valid is SDMA in a breed specific situation

Graham Bilbrough — Fri, 24 Mar 2017 19:42:36 GMT

Hi, Martin and others

Sorry for the slow reply. I am living and working in the USA now. Let me get in contact with a colleague, with more SDMA knowledge, and one of us will get back to the forum. This will probably be after the weekend.

Thanks

Graham

RE: Heresy question- How valid is SDMA in a breed specific situation

Sarah Keir — Fri, 24 Mar 2017 16:11:18 GMT

Here is the IRIS group's current comment on SDMA:

"Interpreting Blood Concentrations of Symmetric Dimethylarginine (SDMA) in CKD

SDMA concentrations in blood (plasma or serum) may be a more sensitive biomarker of renal function than blood creatinine concentrations. A persistent increase in SDMA above 14 µg/dl suggests reduced renal function and may be a reason to consider a dog or cat with creatinine values <1.4 or="" 1="" 6="" mg="" dl="" respectively="" as="" iris="" ckd="" stage="" em="">

In IRIS CKD Stage 2 patients with low body condition scores, SDMA ≥25 µg/dl may indicate the degree of renal dysfunction has been underestimated. Consider treatment recommendations listed under IRIS CKD Stage 3 for this patient.

In IRIS CKD Stage 3 patients with low body condition scores, SDMA ≥45 µg/dl may indicate the degree of renal dysfunction has been underestimated. Consider treatment recommendations listed under IRIS CKD Stage 4 for this patient.

These comments are preliminary and based on early data from the use of SDMA in veterinary patients. We expect them to be updated as the veterinary profession gains further experience using SDMA alongside creatinine, the long-established marker in diagnosis and monitoring of canine and feline CKD."

RE: Heresy question- How valid is SDMA in a breed specific situation

Martin Atkinson — Fri, 24 Mar 2017 14:24:36 GMT

[quote user="Aine Seavers"]a bit like how Idexxx has ignored my question above[/quote]Idexx are good at producing tests with little or no diagnostic value and not having full answers. The SNAP feline NT-proBNP test is a case in point: the cut off for a +ve is 170pmol/l when below 100 is considered normal and >270 suggests cardiac failure but anything else in between is equivocal - it tells you nothing. And when questioned even customer service didn't know what the cut off of the test was without going away and researching it!! I do however have great faith in their reference laboratory Cardiopet test and Graham Bilborough has been very supportive in the past - where are you now Graham?

RE: Heresy question- How valid is SDMA in a breed specific situation

Aine Seavers — Fri, 24 Mar 2017 04:03:05 GMT

many tx, I will have a good look

RE: Heresy question- How valid is SDMA in a breed specific situation

David Mills — Fri, 24 Mar 2017 01:10:23 GMT

There was a thread on this a while ago. It's flawed and the evidence is weak and the specificity low. Available on search.

Another idexx marketing triumph, or not - a bit like u2 album straight into your iTunes library. File under angiostrongylus snap - go look at the field performance, no better than flotation.

RE: Heresy question- How valid is SDMA in a breed specific situation

Aine Seavers — Thu, 23 Mar 2017 22:14:23 GMT

yep-so on the same page on thinking on this one-a test in search of a disease -the aussies here call it a Clayton- a thing you are having when you are not-a Clayton's test-ie not the real deal.

RI is reference interval-we used to say reference range-another semantic to confuse us all.

The comments on other lists is again the same thing-ignore the test- a bit like how Idexxx has ignored my question above;-)-I cant be the first vet to ask these questions-which suggests there are no answers as no data-which to me means any interpretation of the test is very tenuous. However I will be overjoyed to be proven wrong and for Idexx to be able to provide the data on all our concerns.

RE: Heresy question- How valid is SDMA in a breed specific situation

Iain Richards — Thu, 23 Mar 2017 20:40:49 GMT

Well, this is new to me! So a bit of CPD and I can reflect that it is a new test that I haven't seen sent/spec values for, so may be of questionable value. What's RI though?

RE: Heresy question- How valid is SDMA in a breed specific situation

Martin Atkinson — Thu, 23 Mar 2017 12:20:55 GMT

[quote user="mariette asselbergs"]She said that there was no advantage of SDMA testing because it was the same as if you would use a lower cut off point for creatinine. [/quote]I didn't go to that session but I've heard similar from other 'experts'.

SDMA seems like a test created to solve a problem which doesn't exist, promoted to detect renal failure before increased levels in BUN and creatinine. I can see some value in testing patients before/during treatment with potentially nephrotoxic drugs so as to move with more caution but in a normal animal with suspected renal disease WTF does it matter and how are you going to deal with the case clinically if other renal/urine values are normal anyway?

RE: Heresy question- How valid is SDMA in a breed specific situation

mariette asselbergs — Wed, 22 Mar 2017 18:53:25 GMT

I went to last year's "breakfast with an expert" at the BSAVA congress.

She said that there was no advantage of SDMA testing because it was the same as if you would use a lower cut off point for creatinine. She only saw an advantage in aimals with very littkle muscle mass, basically cachectic animals, who produce little creatinine.

Mariette

RE: Heresy question- How valid is SDMA in a breed specific situation

Aine Seavers — Tue, 21 Mar 2017 11:09:36 GMT

Excellent suggestion Rob, Hopefully your Graham can put this test into real time clinical application. I am reluctant to take a stable dog off a drug used safely (in countless pets for many decades with no real jumps up re renal issues) just because this new test is outside normal. The specialist center got a reading of 17 and Cr of 11 and bun 5 and recommended considering stopping inderal- I got a 16,11 5 today. The sample was fasted but lipaemic so I am keener on tracking that down the cause of that rather then sdma-so would love to know if lipaemia will interfere. Or indeed if the test will be like TT4 and you need to withdraw certain meds for some time before the test to avoid interference.

There is so much promoted about how this SDMA is the go to test-but the evidence and back ground support knowledge on co-factors of interference and genomics etc just doesnt seem to be widely or easily known/found.

( Propranolol is our go-to drug for Canine cognitiveve disorder dogs since the 1990s -any bloods back have had normal renal bloods and no clinical renal issues despite senior age and many years on the medication). This dog is a young fit lean 3yr old male N Boxer.

RE: Heresy question- How valid is SDMA in a breed specific situation

Rob Davis — Tue, 21 Mar 2017 09:29:02 GMT

No idea, but perhaps Graham Bilbrough will know?