Home >
What is CKD?
> Early
Detection
Overview
-
As discussed on the
What
Happens in CKD? page, it is not normally possible to detect CKD until the cat has
already lost 66-75% of his or her kidney function, although the SDMA test
may offer earlier indications of a problem.
Benefits of Early Detection
It may appear
that there is no real benefit in early detection, because it is not
possible to cure CKD, and knowing at an early stage that your cat has it
may distress you. However, there are in fact some benefits to knowing
early:
CKD early diagnosis (2019) Syme H International Renal Interest Society
explains more about early detection and suggests obtaining baseline
bloodwork when your cat is healthy, so you can monitor trends for your
cat.
Types of Test Available
Glomerular
filtration rate (see
below) is the gold standard for
assessing kidney function in cats. Unfortunately GFR is not easy to
measure in cats, so although I do discuss it below, you are unlikely to be
offered this test unless you attend a vet school.
Historically, the usual way to diagnose CKD
in cats has been
via elevated
creatinine (and to a much lesser extent, BUN or urea) levels in the
blood, and via certain urine tests. However, creatinine does not tend to
rise in CKD cats until 60-70% of kidney function has already been lost,
which means that a cat can actually be in Stage 1 or 2 of CKD according to
the IRIS staging system (see
How Bad is
It?) but still have a creatinine that falls within supposedly normal
limits. In addition, since creatinine is a by-product of muscle and is
higher when a lot of muscle is present, a large
muscular cat may be suspected of having CKD when he does not, whereas a
CKD cat who has lost a lot of weight and muscle might not be diagnosed
promptly.
Because of this, there have been many attempts to find a way of diagnosing
CKD earlier in cats. The SDMA test was introduced in 2015 and
is now routinely offered.
Assessment
of renal function: what can be done in practice (2002) Elliott
J Presentation to
the World Small Animal Veterinary Association Congress
discusses the various methods of detecting CKD.
See
Other Diagnostic Tests to read about studies into the
possible use of ultrasound to diagnose CKD in cats.
Biomarkers of urinary tract disease: potential utilities
(2024) Segev G International Renal Interest Society
discusses the benefits of early detection and mentions some possible
tests, though none of these is widely available as yet apart from the SDMA
test.
The tests fall into the following categories:
Widely
Available Tests
Not Widely Available
Tests
Blood Tests
Most vets will check your cat's
creatinine and
BUN
(or urea) levels. You may also be offered the SDMA test.
SDMA
(Symmetric Dimethylarginine) Test
What is SDMA?
SDMA is a methylated form of
arginine, an
amino acid. It is released when protein is processed, and is
eliminated largely (over 90%) by the kidneys. Because of this, increased levels of SDMA may correlate with the development
of CKD.
One human study,
Symmetrical dimethylarginine: a new combined
parameter for renal function and extent of coronary artery disease
(2006) Bode-Böger SM, Scalera F, Kielstein JT, Martens-Lobenhoffer J,
Breithardt G, Fobker M & Reinecke H Journal of the American Society of
Nephrology 17 pp1228-1134 concluded that "SDMA might be a
useful parameter for detecting patients in very early stages of chronic
kidney disease and for determining their risk for developing
cardiovascular disease."
As mentioned above, creatinine may appear lower than it
truly is if the cat has lost muscle mass. One advantage of the SDMA test
is that, as
Early diagnosis of chronic kidney disease in dogs
and cats: use of serum creatinine and symmetric dimethylarginine
(2016) Grauer GF Today's Veterinary Practice Mar/Apr 2016
states, "In contrast to sCr, SDMA should not be affected by changes in
muscle mass."
The SDMA Test
The SDMA test for cats was developed by
Ohio State University College of Veterinary Medicine and IDEXX
Laboratories,
and became available commercially in 2015.
Comparison of serum concentrations of symmetric
dimethylarginine and creatinine as kidney function biomarkers in cats with
chronic kidney disease (2014) Hall JA, Yerramilli M, Obare E,
Yerramilli M & Jewell DE Journal of Veterinary Internal Medicine
28 pp1676–1683 found that SDMA levels in cats who developed CKD rose above normal by a mean of
17 months before there was an increase in creatinine levels.
IDEXX states that the SDMA test can
therefore potentially detect CKD when up to 40% of function has been lost, whereas
traditionally you could only detect CKD when 60-70% of function had been
lost.
SDMA: How to Run
the Test
The SDMA test can simply be run as part of a standard
blood chemistry blood test from IDEXX. If you are in the USA and your vet
uses IDEXX for blood chemistry panels, the SDMA test should be provided
routinely. If your vet uses in-house testing for most tests but has a
relationship with IDEXX, the test can be ordered separately from the IDEXX
laboratory.
SDMA:
Interpreting the Results
IDEXX have provided the following guidelines for the
test:
|
Measurement |
IDEXX Staging |
|
0-14 ug/dl
|
Normal kidney
function |
|
15-20 ug/dl
|
Early kidney disease |
|
Over 20 ug/dl |
More advanced kidney
disease |
Only 1% of cats will have a reading over 50 ug/dl.
IDEXX recommend that the test should not be run in
isolation but in conjunction with creatinine and urinalysis. This is
particularly true for cats with SDMA and/or creatinine
at the upper end of the normal range.
Determination of age-specific reference intervals for selected serum and
urinary biomarkers in elderly cats (2023) Mortier F, van Leeuwenberg R,
Daminet S & Paepe D Journal of Feline Medicine and Surgery 25(11) looked at
reference ranges (RI or reference intervals) for older cats for values used
in the diagnosis of CKD and hyperthyroidism. The study concludes "For
mature adult and senior cats, azotaemia may be diagnosed at lower sCr levels
than the current RI suggests (eg, ≥167 µmol/l). However, for SDMA, the
current RI may be too low, with some cats having SDMA up to 17.8 µg/dl
without CKD (if USG is normal and there are no other abnormalities). TT4
results in the upper RI range (>45 nmol/l) in this age group may be abnormal
and hyperthyroidism remains possible."
Some people believe the SDMA test may not be accurate
for kittens, but IDEXX have established
a kitten reference interval.
SDMA:
IRIS Staging
IRIS staging of CKD
(2023)
International Renal Interest Society refers to SDMA results in
its staging guidelines. For cats with persistently elevated SDMA readings,
it suggests changing the stage of CKD the cat is deemed to be in as
follows:
|
Creatinine Level |
IRIS Staging
Based
on Creatinine Levels Only |
SDMA Measurement |
Revised
IRIS
Staging |
|
Below 1.6 mg/dl
Below 140 µmol/L |
Stage 1 |
Persistently
over 18 |
Stage 2 |
|
1.6 - 2.8 mg/dl
140 - 249 µmol/L |
Stage 2 |
Persistently
over 25 |
Stage 3 |
|
2.9 - 5.0 mg/dl
250 - 440 µmol/L |
Stage 3 |
Persistently
over 38 |
Stage 4 |
Other Factors
Affecting SDMA
Your vet should rule out
pre-renal causes
(such as dehydration) and
acute kidney injury
(AKI) because SDMA may be elevated in cases of AKI or if any other
condition is present that
reduces blood flow through the kidneys.
Symmetric dimethylarginine in cats with hypertrophic
cardiomyopathy and diabetes (2018)
Langhorn R, Kieler IN, Koch J, Christiansen LB & Jessen LR Journal of
Veterinary Internal Medicine 32(1) pp57-63 looked at SDMA levels in cats
with HCM or diabetes. It concludes "Serum SDMA concentrations in cats with
HCM were not significantly different from those of healthy control cats.
Cats with DM, however, had significantly lower SDMA concentrations than
controls, a finding that needs further investigation and should be kept in
mind when evaluating renal function of cats with this endocrinopathy." I
take this to mean that a cat with both CKD and diabetes might have lower
SDMA levels than if the cat had CKD only.
Feline renal biomarkers: from reference intervals to clinical
application (2022) Mack R
IDEXX Laboratories explains more about SDMA and concurrent
diseases.
Creatinine levels are naturally higher in Birman cats,
which may lead some Birmans to receive an incorrect diagnosis of CKD.
Serum symmetric dimethylarginine and
creatinine in Birman cats compared with cats of other breeds
(2018) Paltrinieri S, Giraldi M, Prolo A, Scarpa
P, Piseddu E, Beccati M, Graziani B & Bo S Journal of Feline Medicine
and Surgery 20(10) pp905-912 found that levels of SDMA are also
higher in Birman cats, though not as much as creatinine. The study states
that Birman cats should be assessed based on SDMA as well as creatinine,
and using a specialised reference range for Birmans.
Symmetric dimethylarginine in
hyperthyroid cats before and after treatment with radioactive iodine
(2020) DeMonaco SM, Panciera DL, Morre WA,
Conway T & Werre S Journal of Feline Medicine and Surgery 22(6)
pp531-538 found that SDMA increases in cats treated with I131 for
hyperthyroidism, and states that SDMA should be considered alongside
creatinine and USG in hyperthyroid cats before treatment.
SDMA: What To Do Next
IDEXX SDMA algorithm
explains what to do next if your
cat has a positive SDMA test. You can also read more about how to manage
your cat's current condition on the
How Bad
is It? page.
SDMA may be useful for helping confirm the CKD
diagnosis, but once your cat has had a positive test, repeating the test
is unlikely to be of value in most cases, though
Early diagnosis of chronic kidney disease in dogs
and cats: use of serum creatinine and symmetric dimethylarginine
(2016) Grauer GF Today's Veterinary Practice Mar/Apr 2016
says that "cats with borderline sCr [creatinine] and/or SDMA concentrations
should be retested: Two weeks after initial testing to confirm the initial
value, Then approximately every 3 months to assess renal function
stability."
Fibroblast Growth Factor 23 (FGF-23)
Fibroblast growth factor 23 (FGF-23) is important for
the regulation of phosphorus levels in the body. Since
phosphorus and
parathyroid hormone (PTH) imbalances are common in CKD, it is possible
that FGF-23 levels may in fact rise before other signs of CKD appear. In
humans, such increases have been identified before any changes in PTH and
phosphorus levels, and it now appears that this also applies to cats..
Fibroblast growth factor 23 (FGF-23) concentrations
in cats with early non-azotemic chronic kidney disease
(2013)
Finch NC, Geddes RF, Syme HM & Elliott J Journal of Veterinary Internal Medicine
27 pp227-233 measured levels of FGF-23 in geriatric cats. The study
found that FGF-23 levels were significantly higher in cats who were
apparently healthy at the start of the study but who subsequently went on
to develop
azotaemia. It also indicated an association between FGF-23 and
secondary hyperparathyroidism.
Relationship
between plasma fibroblast
growth factor-23 concentration and survival times in cats with chronic
kidney disease (2015) Geddes
RF, Elliot J & Syme HM Journal of Veterinary Internal Medicine
29(6) pp1494-1501 states "Plasma FGF-23 is noted to increase early in
the development of CKD, before obvious evidence of hyperphosphatemia. It
is not known if FGF-23 is a uremic toxin or more a surrogate marker for
other causes of uremic toxicity."
This study also found a correlation between FGF-23
levels and survival time, with cats with an FGF-23 level below 700 pg/mL
having a median survival time of 577 days, compared to cats with an FGF-23
level of 3000-10000 pg/mL surviving a median of 277 days. Cats with a
level over 10000 pg/mL had a median survival time of only 38 days.
Fibroblast growth factor 23 -a review with particular reference to the
physiology and pathophysiology of phosphate homeostasis in the cat
(2025) Elliott J & Tang PK Veterinary Journal 309
discusses FGF-23. It describes it as "the hormone that has now become
known as the prime regulator of serum phosphate physiologically and the
key player in the pathophysiology of
MBD of CKD."
Association between serum fibroblast growth factor
and blood calcium levels in chronic kidney disease cats with upper
urolithiasis
(2022) Miyakawa H, Hsu HH, Ogawa M, Akabane
R, Miyagawa Y & Takemura N Journal of Feline Medicine and Surgery
24(12) pp1245-1252 found that increased FGF-23 levels were
associated with hypercalcaemia in cats with both CKD and
kidney
stones.
A
review of the role of fibroblast growth factor 23 in phosphate
homeostasis and the pathophysiology of mineral bone disorder associated
with chronic kidney disease
(2023) Elliott J, Geddes R & Jepson R International Renal
Interest Society states that FGF-23 levels may also be elevated in
cats with chronic inflammation or iron deficiency. Low magnesium levels
may also be a factor.
Recent advances in mineral and bone disorders in CKD
Van den Broek H & Elliott J International Renal Interest Society
has some information about FGF-23.
FGF-23: a new player in the regulation of phosphate
(2015) Elliott J International Renal Interest Society
explains more about FGF-23.
Fibroblast Growth Factor 23 (FGF-23)
and Phosphorus Levels
FGF-23 testing was previously not available to vets,
but IDEXX introduced a
new FGF-23 test in 2022.
IDEXX has an algorithm for when and how to use the FGF-23 test.
The new test is not intended to help with diagnosing
CKD per se; rather, Idexx refers to the new test as a "renal management
biomarker."
FGF-23
(2022) IDEXX Laboratories Diagnostic Update states "FGF-23
is not intended to be used as a core diagnostic tool to
diagnose cats with CKD, but rather it serves as a useful indicator
of the need for therapeutic intervention and potentially in
prognosis." In particular, it may help with the "Early
detection of phosphorus overload and metabolic bone disease in
cats with IRIS CKD Stage 1 and Stage 2."
IRIS treatment recommendations for CKD in
cats
(2023) International Renal Interest Society
recommends using FGF-23 levels to determine whether to start a therapeutic
kidney diet even for a cat whose phosphorus levels appear to be normal.
See
The Importance of Phosphorus Control for more information.
Urine
Tests
Urine
Specific Gravity
Measuring
urine specific gravity may indicate loss of concentrating ability
before anything shows in bloodwork.
However, a cat may have dilute
urine for other reasons, such as
diabetes,
so this is only a guide, not a definitive method of diagnosis. Also, once
a cat is receiving fluid therapy, USG can be rather unreliable.
Urine specific gravity
(2024) Watson ADJ, Lefebvre HP & Elliott J International Renal Interest Society has information on the significance of USG in cats.
Proteinuria
Proteinuria (2024) Grauer GF International
Renal Interest Society explains how
protein in the urine, which is known as proteinuria, is a risk factor for the development of CKD, and also a
factor in
determining the severity of the CKD.
Evaluation of predictors of the development of
azotaemia in cats (2009)
Jepson RE, Brodbelt D, Vallance C, Syme HM, Elliott J. Journal of Veterinary Internal Medicine
23(4)
pp806-13 reports on a group of older cats who were monitored to see if
they developed CKD. The study concludes that "Proteinuria at presentation
was significantly associated with development of
azotemia although causal association cannot be inferred."
Protein in the urine may have causes other than CKD.
There is more information about proteinuria on the
Proteinuria
page.
Urine:PC Ratio
Proteinuria is assessed via the
urine:PC ratio test.
IDEXX Laboratories offers a test in a number of different countries that can calculate the protein:creatinine ratio. It is part of their catalyst 1 test.
A similar test is also available from Antech.
RenalTech
RenalTech is
an artificial intelligence (AI) predictive tool developed by Antech, which
claims it can detect CKD up to two years earlier than other methods, and
with 95% accuracy in some cases. The system assessed the records of more
than 100,000 cats who visited a chain of veterinary clinics three or more
times between 1995 and 2017.
Predicting early risk of chronic kidney disease in
cats using routine clinical laboratory tests and machine learning
(2019) Bradley R, Tagkopoulos I, Kim M, Kokkinos Y, Panagiotakos T,
Kennedy J, De Meyer G, Watson P & Elliott J Journal of Veterinary
Internal Medicine 33(6) pp2644-2656 explains more about how the
tool was developed.
An artificial neural network-based model to predict chronic kidney disease
in aged cats (2020) Biourge V, Delmotte S, Feugier A, Bradley
R, McAllister M & Elliott J Journal of Veterinary Internal Medicine
34(5) pp1920-1931 is a later study along the same lines.
The test results needed to use the tool are ones you would usually be
monitoring anyway:
Cats are placed in one of three categories based on their results:
-
Negative: highly unlikely to develop CKD in the next two years. Run
the tests again in a year.
-
Inconclusive: insufficient certainty to predict the likelihood of
CKD. Run the tests again in 3-6 months.
-
Positive: highly likely to develop CKD in the next two years. Use
IRIS staging guidelines.
The tool is available to vets in the USA who use Antech's reference
laboratory services.
Using RenalTech to improve CKD outcomes and overall feline health
(2025) Ogeer J explains how to use RenalTech.
Glomerular Filtration Rate
Glomerular filtration rate in dogs and cats
(2023) Heiene R & Lefebvre HP International Renal Interest
Society states that the glomerular filtration rate (see
What
Happens in CKD) is "considered the single most useful and sensitive
test of renal function." It is also the best way to detect CKD early
because GFR reduces before a rise in creatinine is apparent. It goes on to
say "Assessment of GFR is therefore pivotal for evaluating severity and
progression of renal diseases, especially chronic kidney diseases (CKD)."
Unfortunately measuring GFR is quite cumbersome,
requiring the injection of contrast agents followed by precisely timed
blood tests. Therefore few vets are able or willing to do it.
Early diagnosis of chronic kidney disease in dogs
and cats: use of serum creatinine and symmetric dimethylarginine
(2016) Grauer GF Today's Veterinary Practice Mar/Apr 2016
states "due to expense, time, and labor, GFR is rarely measured in the
practice setting." GFR measurement is available at most vet schools and I
understand the Royal Veterinary College can do it for around Ł180 (2016
price).
Relationship between serum symmetric
dimethylarginine concentration and glomerular filtration rate in cats
(2014) Braff J, Obare E, Yerramilli M, Elliott J & Yerramilli M Journal of Veterinary
Internal Medicine 28 pp1699–1701, a study conducted by IDEXX,
found a correlation between increased levels of SDMA in cats and a low
GFR. If you are unable to have GFR tested, you might wish to consider the
SDMA test
instead, though this is not as accurate
as GFR testing.
Managing chronic kidney disease: 10
common questions
(2012) Brown SA Presentation to the 83rd FVMA Annual Conference
discusses GFR and how to measure it.
An overview of glomerular filtration testing in dogs
and cats (2011) Von Hendy-Willson
VE & Pressler BM Veterinary Journal 188(2) pp156–165 has a
detailed, albeit technical, overview.
The following tests can be used to directly assess GFR:
Iohexol
Clearance Test
(Plasma Iohexol Clearance
Test)
This test uses iohexol, an iodinated
radiographic contrast medium. Basically, the test measures how long it
takes to clear a measured amount of iohexol from the kidneys,
and this is then used to calculate the GFR. Some people use this test
before opting for one of the more permanent methods of treating
hyperthyroidism.
This test, sometimes referred
to as the Plasma Iohexol Clearance test (PIC) is highly
specialised and only available at a limited number of places in USA such
as the Animal Health Diagnostic Laboratory at Michigan State University; I
am not aware that the test is commercially available in Europe.
Michigan State University Veterinary Diagnostic
Laboratory can run the test for you for
US$120 using
this form. Search for test code 70029 if necessary.
Practical matters: practical ways to
measure GFR in your patients
(2011) Langston CE Veterinary Medicine explains more about
how the test is performed and says "Although
iodine allergic reaction or development of mild reversible acute kidney
failure has been reported in people undergoing this type of test, the risk
in animals appears to be low."
Estimation of glomerular filtration rate via 2- and
4-sample plasma clearance of iohexol and creatinine in clinically normal
catC (2009)
Heiene R, Reynolds BS, Bexfield NH, Larsen S & Gerritsen RJ American Journal
of Veterinary Research 70(2) pp176-85 is a study into
determining appropriate reference ranges. It found that the weight of the
cat is a factor.
Current concepts for the management of chronic renal
failure in the dog and cat - early diagnosis and supportive care (2005)
Sanderson S Presentation to the World Small Animal
Veterinary Association World Congress which mentions this test.
Clinical application of plasma clearance of iohexol
on feline patients (2001) Miyamoto K Journal of Feline
Medicine and Surgery 3(3) pp143-147 fouind that iohexol
clearance detected a reduction in GFR before increases in BUN and
creatinine were apparent. The study also found that the test could be
performed non-invasively in conscious cats.
Inulin
Clearance Test
Like the
iohexol clearance test, the inulin clearance test measures how long it
takes the kidneys to clear a measured amount of a particular substance, in
this case inulin.
This test requires a single IV injection of inulin,
followed by taking a blood sample three hours later. The test is commercially available in Germany.
Some people use this test before opting for one of the more permanent
methods of treating
hyperthyroidism.
Single-injection inulin clearance for routine
measurement of glomerular filtration rate in cats (2003)
Haller M,
Rohner K,
Muller W,
Reutter F,
Binder H,
Estelberger W,
Arnold P
Journal of Feline Medicine & Surgery
5 (3) pp175-81 compared the inulin test to the iohexol clearance
test and concluded that "the inulin clearance test is a valuable tool for
the assessment of renal function in daily practice".
Renal Biomarkers
Biomarkers of urinary tract disease: potential utilities (2024) Segev G
International Renal Interest Society discusses the use of various
biomarkers that might assist with the early detection of CKD, including
ngal.
Clinical application of renal biomarkers (2022) Harris AN & Brown E
Today's Veterinary Practice Sep/Oct discusses renal biomarkers such as
KIM-1 (kidney injury molecule 1).
Back to Page Index
