SDMA test for renal function

RE: SDMA test for renal function

Graham Bilbrough — Mon, 31 Oct 2016 12:07:50 GMT

As there seems to be considerable interest in SDMA’s clinical utility as a biomarker for early kidney disease in cats and dogs I’d like to offer some additional published evidence supporting SDMA and often reiterating the shortcomings of creatinine. IDEXX has been studying SDMA for more than a decade, collaborating with leading veterinary nephrologists, to publish more than 41 peer-reviewed publications and abstracts, to date, with almost as many more SDMA studies underway or planned. I have attached a large list of publications for your convenience.

The early foundational studies of SDMA in healthy patients and cats and dogs with CKD established three key attributes of SDMA that make it a more reliable kidney biomarker than creatinine: 1)It correlates well with GFR,^1,2,3 2) it increases earlier than creatinine, when there is on average a 40% reduction in GFR, compared to creatinine that increases with up to 75% reduction,^1,2,3 and 3)it is more specific for kidney function, as it is less impacted than creatinine by many extrarenal factors, including lean body mass.^4,5 These promising findings led to development of the only validated immunoassay for canine and feline serum and plasma, the IDEXX SDMA™ Test.¹

Diagnosing kidney disease early provides opportunities to intervene and potentially to improve outcomes by addressing causes, such as stones and pyelonephritis, and complications, such as hypertension and proteinuria, that can accelerate kidney damage. Additionally, there is emerging evidence that feeding a renal supportive diet can be beneficial for nonproteinuric, IRIS (International Renal Interest Society) CKD Stage 1 dogs^6,7and cats.⁸Because SDMA helps veterinarians to more reliably diagnose, stage and treat kidney disease we believed it was important to add it to routine chemistry profiles. It was certainly not a decision made in haste or without research into the medicine and practice needs.

Throughout the long process of research and development IDEXX has continued to consult with renal thought leaders, many of whom are part of the IRIS board or have served as officers, and we have shared with them our aggregate patient data, over 5 million IDEXX SDMA results worldwide. IRIS members have placed their confidence in SDMA, incorporating it into the CKD guidelines in 2015 as an adjunct to creatinine for diagnosis of kidney disease and to aid in treating patients with all stages of CKD that may be ‘under staged’ by creatinine. A copy of the updated IRIS guidelines is available here: http://iris-kidney.com/pdf/staging-of-ckd.pdf

and a complete review article on SDMA recently published in the Vet Clinics of North America CKD issue with open access, https://urldefense.proofpoint.com/v2/url?u=http-3A__dx.doi.org_10.1016_j.cvsm.2016.06.010&d=DQIFaQ&c=2do6VJGs3LvEOe4OFFM1bA&r=_hmp2d5uHmEKEadtLv76YuO3ikKIeuFsKD28WYzv1Kw&m=VW1dc0GKFarTJwiYqaMP8j6RvBUy7tmygK1RMH9K99I&s=1_RHVBcZw6dCYLyBnXtNjuR__UMuXKbHiKgvWdqrDX4&e=

When a patient’s SDMA is increased there are some easy steps to action:

• Investigate for an underlying cause of kidney disease, especially more treatable conditions such as infection, obstruction, or exposure to toxins or potentially nephrotoxic drugs, and to look for confounding conditions by assessing hydration status, blood pressure and thyroid status.

• Manage or treat any underlying causes or confounding conditions and implementing practices to avoid future insults to the kidneys; e.g., taking precautions with prescribed drugs and when anaesthetizing the pet.

• Monitor the patient as indicated based on treatments initiated for any identified underlying diseases or confounding conditions.

The attached SDMA Diagnostic Algorithm offers more detail on what to next when SDMA is increased.

I hope this other view of SDMA has been helpful. I’d be happy to chat more as you have questions or comments.

Dr. Graham Bilbrough MA VetMB CertVA MRCVS | Medical Affairs Manager (Chemistry)

IDEXX | One IDEXX Drive | Westbrook, Maine 04092 USA

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.
Hall JA, MacLeay J, Yerramilli M, et al. Positive impact of nutritional interventions on serum symmetric dimethylarginine and creatinine concentrations in client-owned geriatric dogs. PLoS One. 2016;11(4):e0153653.
Hall J, Fritsch D, Yerramilli M, et al. Positive impact of nutritional interventions in client-owned dogs with IRIS stage-1 chronic kidney disease [ACVIM Abstract NU16]. J Vet Intern Med. 2016;30(4):1491.
Hall JA, MacLeay J, Yerramilli M, et al. Positive impact of nutritional interventions on serum symmetric dimethylarginine and creatinine concentrations in client-owned geriatric cats. PLoS One. 2016;11(4): e0153654.

www.vetsurgeon.org/.../09_2D00_81942_2D00_00_2B00_SDMA_2B00_IMM_2B00_Sheet_2B00_Algorithm_2B00_9_5F00_Final_5F00_L.pdf www.vetsurgeon.org/.../SDMA-Articles-and-Abstracts-October-14.pdf

RE: SDMA test for renal function

Andrew Kent — Wed, 12 Oct 2016 13:00:59 GMT

My feelings about SDMA are similar to David's, in that I think it has some interest but we don't know enough about it yet to know what it really means or what to do about it.

There is a tendency to launch tests (with cPLI being an example) based on fairly specific data and make very generalised claims about its use. This can, at best be misleading and, at worst, lead to dangerous misdiagnoses.

The studies are done on a very specifc group of animals so what the real sensitivity/specificity of this test will be when applied to a more general population remains to be seen. My impression so far is that the specificity is likely to be poor as I am seeing mild SDMA elevations in lots of patients who often don't have kidney disease.

Hopefully over the next few years we will build up better experience to know when this is a useful test to run.

Just my thoughts!

Andy

RE: SDMA test for renal function

Robin Grimmer — Tue, 11 Oct 2016 21:43:45 GMT

I wonder whether it will be like the cPLI snap test which often seems to be positive!

RE: SDMA test for renal function

David Mills — Mon, 10 Oct 2016 18:38:38 GMT

The evidence for its use as a early marker is somewhat weak for animals, although there is more in humans.

In cats, the two published studies have a population of 31 between them. The specificity of SDMA was 91% vs 100% for creatinine and the range of rise before creatinine was 0-48 months (mean 17 months - no median is detailed which is worrying with such a range).

SDMA can be increased in various disease states, including cardiac, neoplasia, spinal muscle atrophy and following viral infections. At least 90% is excreted by the kidneys, but there are other routes (c.f. creat which is >98% excreted by kidneys and produced at a constant rate, which may drop in muscularly poor cats).

There does appear to be a correlation between SDMA and dveloping renal disease but from the studies available it cannot be said it definitively picks up all cases that would only be picked up with increased creatinine. Further, there is no evidence in cats (or dogs) that treating non-azotaemic animals with high SDMA (despite what IDEXX say) is beneficial - even the authors of the two studies say this.

At the moment, the jury still appears to be out on this; I'm not convinced that it is quite the golden test it is being promoted as. With my skeptic hat on, this may be a case of treating risk rather than disease, which is a worrying development that has been seen with EBM in humans.

Studies are here and are open access:

http://onlinelibrary.wiley.com/doi/10.1111/jvim.12446/full

http://onlinelibrary.wiley.com/doi/10.1111/jvim.12445/full

RE: SDMA test for renal function

Stephanie Wellings — Mon, 10 Oct 2016 18:04:30 GMT

One possibility if only SDMA was raised (and everything else WNL including urinalysis/culture) would be just to screen the cat more often (urine tests q3-6 months or so and bloods 6-12mo) so you pick up the time when it becomes azotaemic/isosthenuric nice and swiftly and treat then. It would be nice for them to do some studies about whether early treatment improves the prognosis in these cases....

RE: SDMA test for renal function

MattB — Mon, 10 Oct 2016 14:19:39 GMT

What you could do is measure Glomerular Filtration Rate through Iohexol clearance, and see if that is altered; that can give a better indication of renal function in pets with unclear SDMA or SG results

RE: SDMA test for renal function

Robin Grimmer — Mon, 10 Oct 2016 12:44:24 GMT

Good question. I had a case passed over to me where a relatively young cat (5yo) had had bloods which showed a slightly increased urea and SDMA, normal creatinine and phosphate. Urine SG was 1.045. As the urine SG was fine I just said to monitor for now and repeat bloods and urinalysis in 6 months. But should I have done any different?