New Test for The Early Diagnosis of Chronic Kidney Disease By: Hanne Friis Lund, DvM, Nordic Medical Affairs Manager, IDEXX

Chronic Kidney Disease (CKD) is one of the most
prevalent conditions in dogs and cats. Statistics from
the US have shown that 1 out of 10 dogs and 3 out of
10 cats will develop CKD within their life span, prevalence
obviously increasing with age.
The big challenge with these CKD patients is that the
cause is usually incurable and medical care is mainly
about prolonging life and making the animal as comfortable
as possible.

The earlier we can intervene with diet and medical
treatment, the longer the animal is expected to live.
Diagnosing CKD in very late stages gives veterinarians
little chance to make a difference and that is what we
often see in veterinary practice – the patient being presented
to us when it is actually too late to make a
difference.

Diagnosing CKD
The classical diagnostic tools in diagnosing renal failure
consist of a minimum database including:
Biochemistry and electrolytes:
Elevated BUN and creatinine
(azotaemia), electrolyte disturbances
such as high phosphate
and low potassium in the severe
cases. Low total protein and high
cholesterol are also common
findings.
Hematology: CKD patients are
often presented with a non-regenerative
anaemia and a stress
leukogram.
Urinalysis: Lack of urine concentrating
ability: low urine specific
gravity (USG) and proteinuria is
common but not always seen
and, depending on the renal pathology,
casts may be seen.

Diagnostic imaging and blood pressure: CKD is the
most common cause of elevated blood pressure in
the dog and cat. Imaging is vital to determine if there
are reversible causes such as renal or ureteral urolithisasis,
renal neoplasia (lymphoma) and also to evaluate
renal parenchyma and size.

Of the biochemistry parameters, creatinine is by far
the most specific parameter for renal function as it
is primarily excreted through the kidneys. The challenge
is that is only increases fairly late in the disease
process (>75% renal dysfunction) meaning that up to
75% of the function has been lost before creatinine is
actually elevated beyond reference intervals.
Creatinine can vary greatly between different animals
and is impacted by factors such as: lean body mass,
diet, time of day and breed. For instance oriental cat
breeds such as the Burmese cat have naturally quite
high creatinine levels without any renal pathology.
On the other hand small dog breeds with little lean
muscle mass will have a significantly lower creatinine
than highly muscled dogs. This parameter is thus better measured against “individual normal” than population
normal ranges. The sensitivity of creatinine for
diagnosing renal failure increases significantly if we
establish the patient’s own baseline intervals as that
enables us to trend creatinine and thereby detect persistent
increase in creatinine.

Gold standard in evaluating kidney function
The absolute gold standard in evaluating kidney function
in a patient is to perform a clearance test for the
calculation of Glomerular Filtration Rate (GFR).
Iohexol and inulin clearance are both looked upon as
gold standard tests and a reliable exogenous creatinine
clearance test has also been commercially available
for some years. The challenge of doing regular
clearance tests in veterinary practice is that is often requires
special equipment, it takes time, as blood and
urine has to be collected several times within a given
time interval and it is a costly diagnostic procedure.
For these reasons, although available, it is performed
very rarely in veterinary practice outside of referral
hospitals and university hospitals.
The big desire for many years has therefore been to
find a single test that could give a valid estimate of the
GFR, earlier in the course of renal deterioration than
creatinine, without doing an actual clearance test.

SDMA and early diagnosis
SDMA is an abbreviation for Symmetrical Dimethyl Arginine.
It is not a new test as such, as it has been used
to evaluate renal function in humans for many years.
It is new to veterinary diagnostics and has now been
validated for use in dogs and cats. A veterinary specific
analysis has been created and released this year, the
IDEXX SDMA™.

SDMA is created by methylation in arginine in any
nucleated cell during protein production. SDMA is
released into the blood stream and excreted only
through the kidneys. This means that the level if SDMA
in the blood equals the kidney’s filtration rate.
Veterinary research on this parameter started about
a decade ago and IDEXX laboratories has worked intensely
with different universities and the International
Renal Interest Society (IRIS) to look further into this.
Hills nutrition has played a very vital role as a great
deal of the validation studies has been done on their
pet colony.

The three key attributes of SDMA
• It correlates with GFR, hence it is a biomarker for
kidney function
• It is specific for kidney function
• It is an earlier indicator of renal dysfunction.
Being specific for renal function means that SDMA is
not impacted by lean body mass, breed, age or sex.
Nor is it impacted by arginine levels in the body, liver
function and diet.

The independence of lean body mass is in particular
interesting as when patients start going into renal
failure, often they lose weight which can falsely decrease
the creatinine concentration, SDMA will not be
impacted by this.

Being and earlier indicator of renal disease than creatinine
is also a very promising feature. Studies have
shown that in average SDMA is significantly increased
when 40% of the kidney function is lost as opposed
to creatinine being increased when 75% is lost. SDMA
has also been seen to be elevated when as little as
25% of the kidney function is lost.
This enables us to detect these sub-clinical
CKD patients much earlier. Studies
together with Hills showed that in average
SDMA is increased 9 months earlier
than creatinine in dogs and 17 months
earlier than creatinine in cats. Seventeen
months is a long time in a feline life.
Having this marker available now gives
us the unique chance to start studying
what will happen to survival if we start
intervening earlier in the disease process.
The diet studies by Hills showed significant
prolongation of life when animals
in IRIS stage 2/3 disease were fed a restricted
protein renal diet. We can now
evaluate how much it then changes
with earlier detection and intervention.

Availability and use in practice
IDEXX SDMA™ is currently available through the
IDEXX reference laboratories worldwide. It is incorporated
in any profile containing creatinine and also as
a stand-alone test if one has done the initial work up
in the clinic and wishes to add SDMA to the profiling.
When to measure SDMA?
As SDMA correlates with GFR the indications for
measuring SDMA would be any patient where one
wants to know what the GFR is. That could be be either
to diagnose early CKD or to rule –out early CKD
as a concurrent disease in other illnesses.
SDMA is a part of your diagnostic toolbox and should
always be interpreted together with creatinine, urinalysis
and the clinical picture. In significantly dehydrated
animals, the GFR will be decreased because of the viscosity
of the blood, hence SDMA will also be falsely
elevated. Therefore if you have dehydrated patients, it
makes better sense to wait until after re-hydration to
measure SDMA.
Suggested patient types for SDMA measurement
• Pu/Pd patients without azotaemia where there is
suspicion of CKD
• For sub-staging CKD according to the IRIS staging
guidelines (see: www.iriskidney.com)
• In particular feline patients with vague symptoms
that could be related to CKD
• Patients with acute renal disease where it is desired
to monitor progression
• Patients with lower urinary tract diseases where
there is suspicion of ascending infection
• Senior patients where preventative care and wellness
blood-testing is being done
• Patients in treatment with NSAID or other drugs
that can potentially damage renal function
• Patients with Pu/Pd of other causes where one
wishes to rule out concurrent kidney disease
• Hyperthyroid cats before and during medical
treatment
• Pre-anaesthetic screening in at-risk patients
• Monitoring of at-risk patients (certain breeds)
Experiences from other countries
IDEXX SDMA™ was released in the US in the summer
of 2015. Since then more than a million SDMA tests
have been performed. Looking at the data gained form
this, an even higher prevalence of renal disease than
previously known has been demonstrated, supporting
the theory that renal disease is underdiagnosed.
The majority of the cases detected with SDMA are IRIS
stage 1 and 2, thus they would not necessarily be diagnosed
based just on a creatinine level.
In particular in the older patients we see a higher prevalence
of tests results where SDMA is elevated and
creatinine normal. This is most likely due to the fact
that older patients lose muscle mass, and thereby
creatinine is lowered but renal disease is in fact present.
SDMA is a new test and we are still learning. A great
deal of research continues world-wide and currently
there are studies being performed on topics such as:
SDMA and the hyperthyroid cat, SDMA and cardiac
function, SDMA in acute renal failure together with
other acute renal biomarkers, SDMA as predictor of
bone marrow suppression in patients undergoing
chemotherapy etc.
The results so far are very promising and the coming
years will show how this early diagnosis affects the life
of renal patients.

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