IRIS Staging of CKD (modified 2016)

1. Staging of CKD based on blood creatinine concentration

Staging is undertaken following diagnosis of chronic kidney disease (CKD) in order to facilitate
appropriate treatment and monitoring of the patient.
Staging is based initially on fasting blood creatinine concentration, assessed on at least two
occasions in the stable patient. The patient is then substaged based on proteinuria and blood
pressure.

Separate but related algorithms for staging and substaging CKD in cats and dogs are available
on pages 6 - 9 of this document.

Using these criteria, some empirical recommendations can be made about the type of
treatment it would be logical to use for these cases. In addition, predictions based on clinical
experience might be made about the likely response to treatment.

Stage Blood Creatinine Comments

μmol/l
mg/dl
Dogs Cats
At Risk <125 <140 History suggests the animal is at increased risk of
<1.4 <1.6 developing CKD in the future because of a number
of factors (such as, exposure to nephrotoxic drugs,
breed, high prevalence of infectious disease in the
area, or old age).
1 <125 <140 Nonazotemic. Some other renal abnormality
<1.4 <1.6 present (such as, inadequate urinary
concentrating ability without identifiable nonrenal
cause, abnormal renal palpation or renal imaging
findings, proteinuria of renal origin, abnormal renal
biopsy results, increasing blood creatinine
concentrations in samples collected serially).
2 125-180 140-250 Mild renal azotemia (lower end of the range lies
1.4-2.0 1.6-2.8 within reference ranges for many laboratories, but
the insensitivity of creatinine concentration as a
screening test means that animals with creatinine
values close to the upper reference limit often
have excretory failure). Clinical signs usually mild
or absent.
3 181-440 251-440 Moderate renal azotemia. Many extrarenal clinical
2.1-5.0 2.9-5.0 signs may be present.
4 >440 >440 Increasing risk of systemic clinical signs and
>5.0 >5.0 uraemic crises
Note these blood creatinine concentrations apply to average
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 IRIS Staging of CKD (modified 2016)

Symmetric dimethylarginine (SDMA) and IRIS CKD guidelines

IRIS CKD staging is based currently on fasting blood creatinine concentrations, but there
are indications that SDMA concentrations in blood plasma or serum may be a more
sensitive biomarker of renal function. Accordingly, if blood SDMA concentrations are
known, some modification to the guidelines might be considered, as follows:

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 1.
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.

SDMA assays are offered by a number of laboratories throughout the world. The
methodology used has not yet been standardized and the recommendations made above
are based on the proprietary methodology offered by Idexx Laboratories Ltd.

2a. Substaging by Proteinuria

The goal is to identify renal proteinuria having ruled out post-renal and pre-renal causes.

Standard urine dipsticks can give rise to false positives therefore practitioners should
consider using a more specific screening test such as the sulphosalicylic acid
turbidometric test.

The urine protein to creatinine ratio (UP/C) should be measured in all cases, provided
there is no evidence of urinary tract inflammation or hemorrhage and the routine
measurement of plasma proteins has ruled out dysproteinemias. Ideally staging should
be done on the basis of at least two urine samples collected over a period
of at least 2 weeks.

UP/C Value Substage

Dogs Cats
<0.2 <0.2 Non-proteinuric
0.2 to 0.5 0.2 to 0.4 Borderline proteinuric
>0.5 >0.4 Proteinuric

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 IRIS Staging of CKD (modified 2016)

Patients that are persistently borderline proteinuric should be re-evaluated within 2

months and re-classified as appropriate.

UP/Cs in the non-proteinuric or borderline proteinuric range may be categorized as

‘microalbuminuric’. The significance of microalbuminuria in predicting future renal health
is not understood at present. IRIS’ recommendation is to continue to monitor this level of
proteinuria.

Proteinuria may decline as renal dysfunction worsens and so may be less frequent in
animals in Stages 3 and 4.

Response to any treatment given to reduce glomerular hypertension, filtration pressure,

and proteinuria, should be monitored at intervals using UP/C.

2b. Substaging by Arterial Blood Pressure

Patients should be acclimatized to the measurement conditions and multiple
measurements taken. The final classification should rely upon multiple systolic blood
pressure determinations, preferably done during repeated patient visits to the clinic on
separate days, but acceptable if during the same visit with at least 2 hours separating
determinations. Patients are substaged by systolic blood pressure according to the
degree of risk of target organ damage, and whether there is evidence of target organ
damage or complications.

Systolic Blood Blood Pressure Risk of FutureTarget

Pressure mm Hg Substage Organ Damage
<150 Normotensive Minimal
150-159 Borderline hypertensive Low
160-179 Hypertensive Moderate
≥180 Severely Hypertensive High

However, some breeds, particularly sight hounds, tend to have higher blood pressure than
other breeds. It is preferable to use breed-specific reference ranges if available. The
classification of risk of future target organ damage in “high-pressure breeds” might be
adjusted as follows:

Minimal risk – systolic pressure <10 mm Hg above the breed-specific reference range

Low risk – systolic pressure 10-20 mm Hg above the breed-specific reference range

Moderate risk – systolic pressure 20-40 mm Hg above the breed-specific reference range

High risk – systolic pressure >40 mm Hg above the breed-specific reference range.

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 IRIS Staging of CKD (modified 2016)

As with proteinuria, in the absence of evidence of existing target organ damage,

demonstration of persistence of blood pressure readings within a particular category is
important. ‘Persistence’ of increase here should be judged on multiple measurements made
over the following timescales in these blood pressure substages:
Hypertensive – systolic blood pressure 160 to 179 mm Hg measured over 1 to 2 months

Severely hypertensive – systolic blood pressure

≥180 mm Hg measured over 1 to 2 weeks.

3. Revision of staging and substaging after treatment

The stage and substages assigned to the patient should be revised appropriately as changes
occur. For example, a substantial increase in blood creatinine concentration might warrant
reassignment to a higher stage to reflect the new situation.

Similarly, if antihypertensive (or antiproteinuric) treatment has been instituted, the patient’s
classification on re-evaluation should be adjusted if necessary to reflect the new blood
pressure (or UP/C) rather than the original status, with the addition of an indication that the
current classification is affected by treatment.
The following two examples illustrate the process of revision, where ‘treating’ is used as an
indicator of ongoing treatment.

Example 1
Cat before treatment
Creatinine 200 µmol/l (2.3 mg/dl)
UP/C 0.3
Systolic blood pressure 200 mm Hg
Classification – IRIS CKD Stage 2, borderline proteinuric, severely hypertensive.
Same cat after antihypertensive treatment
Creatinine 300 µmol/l (3.4 mg/dl)
UP/C 0.3
Systolic blood pressure 155 mm Hg
New classification – IRIS CKD Stage 3, borderline proteinuric, borderline hypertensive
(treating).

Example 2
Dog before treatment
Creatinine 160 µmol/l (1.8 mg/dl)
UP/C 0.8
Systolic blood pressure 155 mm Hg
Classification – IRIS CKD Stage 2, proteinuric, borderline hypertensive.
Same dog after antiproteinuric treatment
Creatinine 170 µmol/l (1.9 mg/dl)
UP/C 0.4
Systolic blood pressure 155 mm Hg
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New classification – IRIS CKD Stage 2, borderline proteinuric possible by
(treating), borderline hypertensive.

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 IRIS Staging of CKD (modified 2016)

Algorithm for Staging of Chronic Kidney Disease in Dogs

History and/or physical examination

suggest chronic kidney disease (CKD)

Measure blood creatinine

Creatinine Creatinine Creatinine

<125 µmol/l 125 – 180 µmol/l >180 µmol/l
<1.4 mg/dl 1.4 – 2.0 mg/dl >2.0 mg/dl

Measure urine Measure urine

specific gravity specific gravity
Firm Firm
evidence of evidence of
CKD present CKD absent

<1.030 ≥1.030 Pre- or Renal

post-renal azotaemia
Stage 1 azotaemia
Substage by
UP/C & BP Radiographs and Clinical
ultrasound, UP/C, BP evaluation
and urine culture Stage 3 or 4
Substage by
UP/C & BP
Radiographs
and
ultrasound, Normal: re-evaluate If underlying
UP/C, BP and within 2 months systemic
urine culture abnormalities, correct Institute
Abnormal: Stage 2 and re-evaluate treatment
Substage by UP/C within 6 months
& BP

Correct underlying
Institute
abnormalities and
management
Institute treatment re-evaluate immediately
plan for
Stage 1
patients

Re-evaluate in 2-3 months,

then every 3 months if
creatinine rising; every 3-6 IRIS website made
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 IRIS Staging of CKD (modified 2016)

Algorithm for Staging of Chronic Kidney Disease in Cats

History and/or physical examination

suggest chronic kidney disease (CKD)

Measure blood creatinine

Creatinine Creatinine Creatinine

<140 µmol/l 140– 250 µmol/l >250 µmol/l
<1.6 mg/dl 1.6 – 2.8 mg/dl >2.8 mg/dl

Measure urine Measure urine

specific gravity specific gravity
Firm Firm
evidence of evidence of
CKD present CKD absent

<1.035 ≥1.035 Pre- or Renal

post-renal azotaemia
Stage 1 azotaemia
Substage by
UP/C & BP Radiographs and Clinical
ultrasound, UP/C, BP evaluation
and urine culture Stage 3 or 4
Substage by
UP/C & BP
Radiographs
and
ultrasound, Normal: re-evaluate If underlying
UP/C, BP and within 2 months systemic
urine culture abnormalities, correct Institute
Abnormal: Stage 2 and re-evaluate treatment
Substage by UP/C within 6 months
& BP

Correct underlying
Institute
abnormalities and
management
Institute treatment re-evaluate immediately
plan for
Stage 1
patients

Re-evaluate in 2-3 months,

then every 3 months if
creatinine rising; every 3-6
months if creatinine stable IRIS website made
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 IRIS Staging of CKD (modified 2016)

Algorithm for Substaging by Proteinuria

CKD diagnosed & staged 1-4

Urine dipstick examination

Questionable proteinuria; Non-proteinuric

Urinalysis with sediment examination

Sediment Sediment
abnormal/’active’ ‘inactive’/
unremarkable/
hyaline casts

Conduct further
work-up (eg rule
out lower urinary
tract disease) Determine UP/C

Cat Dog

UP/C <0.2 UP/C >0.4* UP/C <0.2 UP/C >0.5*

Non- Proteinuric Non- Proteinuric
proteinuric proteinuric

UP/C 0.2 - 0.4* UP/C 0.2 - 0.5*

Borderline Proteinuric Borderline Proteinuric
Re-evaluate within 2 months Re-evaluate within 2 months

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 IRIS Staging of CKD (modified 2016)

Algorithm for Substaging by Blood Pressure

(risk of target organ damage from hypertension)

CKD diagnosed & staged 1-4

Measure blood pressure (BP)

Systolic BP Systolic BP Systolic BP

< 150 mm Hg 150-179 mm Hg ≥180 mm Hg
(or <10 mm Hg above (or 10-40 mm Hg above (or >40 mm Hg above
reference range for breed) reference range for breed) reference range for breed)

Minimal Risk
of target organ damage Clinical Evaluation Clinical Evaluation

No extra-renal Extra-renal No extra-renal Extra-renal

evidence of evidence of evidence of evidence of
hypertension hypertension hypertension hypertension
(retinopathy and/ (retinopathy and/
or left ventricular or left ventricular
hypertrophy) hypertrophy)

Low to Low to High Risk High Risk

Moderate Risk Moderate Risk of target organ of target organ
of target organ of target organ damage damage with
damage damage with complications
complications Re-evaluate
Re-evaluate within 1-2 weeks
within 2 months

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