Dr. Rosie DVM

IRIS Staging System for Chronic Kidney Disease

Adapted from the IRIS education article by J Elliott (London, UK) and J White (Sydney, Australia). The stage values, substaging, and guidance on disagreeing creatinine and SDMA results have been updated to the IRIS staging guidelines as modified in 2026.

About the IRIS Staging System

The International Renal Interest Society (IRIS) was formed in 1998. An early aim was to develop a staging system for chronic kidney disease (CKD) in dogs and cats, to make it easier for the veterinary community to communicate about the diagnosis and management of this complex syndrome. At the time of writing, the IRIS Board had 14 members from 10 countries. The staging system was first used by IRIS Board members, refined on the basis of that use, and further modified in light of feedback from the American and European Societies of Veterinary Nephrology and Urology.

The IRIS Board has since reviewed the system in light of publications on new biomarkers of kidney disease. With growing evidence and experience of the usefulness of symmetric dimethylarginine (SDMA) as a surrogate marker of glomerular filtration rate (GFR), the Board decided to incorporate SDMA into the staging system. The IRIS CKD staging process should always be viewed as a work in progress that will continue to be modified as experience accumulates and new information becomes available. When staging, it is therefore important to use the most recent version of the system, which is published on the IRIS website.

It is hoped that widespread use of this staging system, and the reporting of accurately staged case series including treatments and outcomes, will improve our understanding of the natural history of CKD in dogs and cats and help identify better ways to manage it. For the individual practitioner, consistent and accurate use of IRIS staging should provide useful prognostic information and identify the likely consequences of CKD that will need to be managed at each stage.

A challenge for all of us is to find ways to recognize kidney disease earlier, before clinical signs appear, so that any available measures (prevention, treatment, or monitoring) that might slow progression and prevent complications can be started. This is why new early biomarkers of CKD continue to be actively researched, as reflected in recent updates to the staging system. More detail is available in our articles on risk factors for CKD, early diagnosis of CKD, and creatinine, UPC, and SDMA in the early diagnosis of CKD.

Diagnosis of CKD

It is important to understand that the IRIS CKD staging system is not a way of diagnosing CKD. The logical steps to a diagnosis of CKD must happen before a patient is staged. This section is not comprehensive, but it highlights some important principles in reaching a diagnosis before applying the staging system.

Diagnosing CKD requires integrating the history, physical examination, laboratory data, imaging findings, and, where indicated, histopathology. A diagnosis of CKD also assumes that the abnormalities are persistent and that no pre-renal or post-renal cause can be identified.

CKD can show up as abnormalities in one or more of the kidney's functions, or in its structure:

Abnormal kidney function, with a reduced glomerular filtration rate: azotemia (a build-up in the blood of nitrogenous products normally excreted by the kidney), or progressive increases in serum creatinine or SDMA over time, even when these changes occur within the reference intervals.
Abnormal kidney function, with loss of normal glomerular function: persistent proteinuria of renal origin.
Abnormal kidney function, with loss of normal tubular function: loss of urine concentrating ability, shown by an inappropriate urine specific gravity once non-renal causes of increased urination and thirst have been excluded, or inappropriate tubular loss of potassium, bicarbonate, glucose, or amino acids. In the absence of azotemia, a urine specific gravity below 1.035 in a cat, particularly one fed a dry diet, is likely to indicate a kidney abnormality. In dogs, a urine specific gravity below 1.030 is not uncommon in dogs with normal kidney function, so it is less reliable as an early sign of kidney disease.
Abnormal kidney structure: kidney cysts, kidney stones (uroliths), or neoplasia.

In many dogs and cats, especially those with advanced disease, more than one of these abnormalities will be present to confirm the diagnosis. For example, many of these patients develop azotemia together with inappropriately dilute urine.

However, patients in the earlier stages of CKD may have only one abnormality. For example, dogs and cats with proteinuric kidney disease may not be azotemic and may keep their ability to concentrate urine. Conversely, many older dogs and cats with CKD lose their ability to concentrate urine before they develop overt azotemia. Evidence suggests that a persistently increased SDMA (above 14 µg/dL) precedes the rise in serum creatinine in dogs and cats, so a diagnosis of CKD can be based on this finding alone. However, other patient factors, such as age, urine concentrating ability, breed, and the urine protein-to-creatinine ratio (UPC), should be used to support the diagnosis or make it less likely, depending on what they show. The sensitivity of SDMA for detecting early CKD is undoubtedly high, based on the published literature, but there is usually a trade-off between sensitivity and specificity. The specificity of SDMA has not been well defined, and its positive predictive value, that is, the ability of a persistently increased SDMA to predict the presence of CKD and later clinically evident CKD, is likely to be lower in the general populations of dogs and cats screened for kidney disease by practitioners. IRIS expects research in the coming years to define the positive predictive value of an SDMA above 14 µg/dL on its own for predicting later clinically evident CKD in dogs and cats from the general population.

Selecting Dogs and Cats to Be Staged

The IRIS staging system applies only to dogs and cats with stable CKD. Staging is not appropriate in patients whose blood creatinine or SDMA is changing dramatically over a short period. The same applies when the diagnosis of kidney disease is based on proteinuria or loss of urine concentrating ability: these changes must be persistent, and non-renal (pre-renal or post-renal) causes must have been ruled out. If a patient's history, physical examination, and laboratory findings are all compatible with CKD, short-term stability of kidney function can be documented by rechecking serum creatinine, SDMA, or ideally both, in 2 to 4 weeks. Changes of less than 20% to 25% indicate a relatively stable GFR, rule out subclinical dehydration, and allow the patient to be staged. Patients whose history is compatible with an episode of acute kidney injury (see our article on differentiating acute kidney injury from chronic kidney disease) may need much longer for their kidney function to stabilize and should be monitored for 3 months before staging.

For example, when investigating an azotemic dog or cat (with increased blood creatinine or SDMA), first determine whether the cause is:

pre-renal,
primary intrinsic kidney disease, or
post-renal.

Then, if the cause is primary intrinsic kidney disease, determine whether the kidney disease is:

acute,
decompensated chronic (sometimes called "acute on chronic"), or
chronic.

Again, it is only appropriate to stage patients with stable CKD using this method. A dog or cat with acute kidney injury may stabilize into CKD after up to 12 weeks of management, at which point it can be staged. Before then, because the patient's condition is changing rapidly and the situation is acute, the IRIS AKI grading system should be applied, and pre-renal (volume-responsive) and post-renal azotemia should be identified, so that the patient can be monitored closely and treatment adjusted to protect the kidneys from further acute damage where possible (see the AKI grading section of our article on IRIS guidelines).

Staging on Blood Creatinine and SDMA

A blood marker that reflects the functioning kidney mass is extremely useful for staging CKD. The ideal marker is:

Produced at a stable rate that is unaffected by age and disease status
Freely filtered at the glomerulus and neither reabsorbed nor secreted by the tubules, so that its rate of excretion in urine depends on the glomerular filtration rate
Not metabolized or eliminated from the body by any route other than the kidneys

For any such marker, the blood concentration is inversely related to GFR: at a steady state, the concentration is determined by its production rate divided by its clearance. The relationship between concentration and GFR is therefore curved rather than straight, which means that changes in the blood concentration of any surrogate marker of GFR are small in the early stages of CKD.

Traditionally, the marker has been blood creatinine. As well as its curvilinear relationship with GFR, blood creatinine has several well-recognized limitations that make it relatively insensitive as an early indicator of CKD, and these were taken into account when the staging system was devised:

Many current creatinine reference intervals for healthy dogs and cats are wide enough to include patients with mild to moderate kidney disease.
Some of the variation in "normal" creatinine values between healthy dogs and cats is due to variation in GFR, which will be true for any surrogate marker.
Other variation relates to muscle mass, which accounts for significant differences between dog breeds, for example.
Diagnostic laboratories use different methods to measure creatinine, some of which also measure non-creatinine chromogens. There is currently no standardization of blood creatinine measurements across veterinary diagnostic laboratories.
Eating meat-based diets leads to absorption of creatinine after meals, so blood samples for creatinine should be collected after a fast, ideally of 12 hours.

Determining a patient's individual normal creatinine concentration may be more appropriate than using the population-based reference interval, and it allows earlier detection of declining kidney function than single creatinine measurements do.

Because of these limitations of creatinine, a new surrogate marker of GFR, blood SDMA, was launched by IDEXX Laboratories in 2015. SDMA, a breakdown product of methylated proteins released from all nucleated cells, is a small, positively charged molecule that meets all the criteria listed above for a surrogate marker of GFR. Its production does not depend on muscle mass. At present, the SDMA values in the IRIS CKD staging system are based on the assay offered by IDEXX Laboratories and are therefore standardized to one proprietary method.

The IRIS Board recognizes that there are enough published data on blood SDMA, measured by the IDEXX method, as a marker of functioning kidney mass for SDMA to be included in the IRIS CKD staging system alongside blood creatinine. It is not essential to measure both markers to stage a patient, although that is ideal. Staging can be based on either blood creatinine or SDMA. If both are measured and they indicate different IRIS stages, other patient factors, such as muscle mass, age, breed, and concurrent diseases (see below), may help the clinician decide which stage to assign. If in doubt, the IRIS Board advises assigning the higher stage, to make sure all appropriate actions and treatments are considered.

The blood creatinine and SDMA concentrations that define IRIS CKD Stages 1 to 4 were reached by debate and consensus, based on the clinical experience of the Board members and on data from longitudinal studies. As noted above, they and other elements of staging may be modified in future as more knowledge is gained.

IRIS CKD Stages in Dogs

Stage 1: blood creatinine below 1.4 mg/dL (below 125 µmol/L); SDMA below 18 µg/dL
Stage 2: blood creatinine 1.4 to 2.8 mg/dL (125 to 250 µmol/L); SDMA 18 to 35 µg/dL
Stage 3: blood creatinine 2.9 to 5.0 mg/dL (251 to 440 µmol/L); SDMA 36 to 54 µg/dL
Stage 4: blood creatinine above 5.0 mg/dL (above 440 µmol/L); SDMA above 54 µg/dL

IRIS CKD Stages in Cats

Stage 1: blood creatinine below 1.6 mg/dL (below 140 µmol/L); SDMA below 18 µg/dL
Stage 2: blood creatinine 1.6 to 2.8 mg/dL (140 to 250 µmol/L); SDMA 18 to 25 µg/dL
Stage 3: blood creatinine 2.9 to 5.0 mg/dL (251 to 440 µmol/L); SDMA 26 to 38 µg/dL
Stage 4: blood creatinine above 5.0 mg/dL (above 440 µmol/L); SDMA above 38 µg/dL

SDMA is less affected than creatinine by loss of muscle mass, so it can reveal that creatinine is underestimating the loss of kidney function. When the two markers persistently disagree, IRIS recommends staging and treating the patient at the higher stage:

Dogs: creatinine below 1.4 mg/dL with SDMA persistently above 18 µg/dL, stage and treat as Stage 2. Creatinine of 1.4 to 2.8 mg/dL with SDMA persistently above 35 µg/dL, stage and treat as Stage 3. Creatinine of 2.9 to 5.0 mg/dL with SDMA persistently above 54 µg/dL, stage and treat as Stage 4.
Cats: creatinine below 1.6 mg/dL with SDMA persistently above 18 µg/dL, stage and treat as Stage 2. Creatinine of 1.6 to 2.8 mg/dL with SDMA persistently above 25 µg/dL, stage and treat as Stage 3. Creatinine of 2.9 to 5.0 mg/dL with SDMA persistently above 38 µg/dL, stage and treat as Stage 4.

Understanding the Early Stages

The first two stages of the system reflect the fact that a large proportion of kidney tissue must be damaged before a rise in blood creatinine can be detected against many laboratory reference intervals, and that significant kidney disease can exist without a significant reduction in GFR. Research has shown that blood SDMA rises earlier than blood creatinine in dogs and cats with well-characterized kidney abnormalities that lead to progressive loss of kidney tissue.

These principles explain why Stage 1 includes dogs and cats whose blood creatinine is within the reference interval, and many of these patients also have a blood SDMA within the reference interval. For a patient to be classified in Stage 1, some other abnormality must therefore be found that raises the suspicion of disease in the kidney tissue. This could include:

Inadequate urine concentrating ability without an identifiable cause outside the kidney
Persistent renal proteinuria
Abnormal size or shape of the kidneys on palpation, confirmed by diagnostic imaging
Abnormal kidney biopsy findings
Increasing blood creatinine or SDMA on serial samples in an adequately hydrated patient, even if the values remain within the laboratory reference range

One additional diagnostic criterion for CKD is a persistent increase in blood SDMA above the laboratory reference interval. The upper limit of the reference interval for blood SDMA is 14 µg/dL for both dogs and cats. A blood SDMA persistently above this level is consistent with a diagnosis of CKD, even without any other findings. Dogs and cats with blood SDMA values of 15 to 17 µg/dL are placed in IRIS CKD Stage 1 and managed accordingly. This reflects evidence from published studies that SDMA is a more sensitive early indicator of relatively small reductions in GFR, detecting reductions of as little as 20%.

IRIS CKD Stage 2 also includes some dogs and cats whose blood creatinine is within the reference interval. These patients are diagnosed with CKD on the criteria listed above, including a persistent blood SDMA above 17 µg/dL, again reflecting the evidence that SDMA often rises earlier than creatinine in early CKD. In the revised staging system, the blood creatinine range that places a dog in IRIS CKD Stage 2 was widened so that its upper limit matches the one used for cats, 2.8 mg/dL (250 µmol/L). This was done because the dogs seen in IRIS CKD Stage 3 varied very widely: dogs with serum creatinine in the lower part of the old Stage 3 range often had few or no clinical signs and were better managed according to the Stage 2 recommendations.

Many dogs and cats with CKD pass through all four stages, but some, especially older cats, have kidney disease that progresses little or not at all. These patients may remain in one IRIS stage while another condition becomes the more clinically important and life-limiting problem. Affected patients may be presented at any stage, depending on how observant their owner is and whether regular health screening is being carried out.

The IRIS Board hoped that, over time and with research, it would become possible to adjust the staging system to reflect GFR more closely, either by using individual patient factors to adjust blood creatinine or by applying a more direct measurement of GFR suitable for clinical practice. Neither has yet proved possible, although research continues. The introduction of blood SDMA into the staging system is certainly an advance that should help detect CKD earlier. This is important, because the early stages are when intervention has the best chance of slowing progression and preserving the pet's quality of life by protecting the remaining functioning nephrons.

Discordant Results

No single test can be expected to be an ideal marker of kidney disease in every subgroup of patients. Testing in parallel, measuring both creatinine and SDMA at the same time, improves diagnostic sensitivity (detecting more dogs and cats with early CKD) but is likely to reduce specificity (suspecting CKD in normal patients). How far SDMA's greater sensitivity to reduced GFR lowers specificity has yet to be determined by large longitudinal population studies, although specificity is most likely to be questionable in dogs and cats diagnosed with CKD on the basis of a persistently increased SDMA alone. If the diagnosis is supported by other tests, such as the UPC, blood pressure, or abdominal imaging, the clinician can be more confident in it.

Having two markers for staging CKD means they may sometimes disagree. Based on experience with creatinine and SDMA, discrepancies (one value within the reference interval and the other outside it) are expected in about 9% of dogs and 17% of cats.

Possible causes of these discrepancies include:

Concurrent diseases: as experience with the assay grows, subgroups of dogs and cats may be found in which SDMA is affected by specific diseases. For example, SDMA is not affected by concurrent heart disease in dogs or cats, but it may be increased in hyperthyroid cats and in dogs with hypoadrenocorticism. SDMA can also be increased without any fall in GFR in some conditions, such as lymphoma in dogs and cats, which is one reason it helps to have two markers to interpret together.
Muscle mass: creatinine is affected by muscle mass, so it may be misleadingly low in patients with reduced muscle mass and misleadingly high in very muscular patients.
Biological variation: some normal dogs and cats will inevitably fall outside the 95% reference interval of any assay. In these patients, a normal result on a second test supports normal kidney function.
Breed: the proposed SDMA reference interval for greyhounds is 6.3 to 19.8 µg/dL, and for Birman cats 3.4 to 19.2 µg/dL. Further breed differences may become apparent.
Laboratory technical issues: dogs and cats that have not been fasted may have higher creatinine, and hemolysis interferes with the SDMA assay and produces falsely low results. In addition, using a trend of increasing creatinine or SDMA to diagnose CKD assumes that the same test method is used over time, for example the same laboratory.

When results disagree in diagnosing CKD, IRIS recommends repeating the blood tests in about 2 weeks to confirm the original results, and then about every 3 to 6 months depending on other patient factors, remembering that a diagnosis of CKD requires all the available laboratory data to be considered and the changes to persist over time in an adequately hydrated patient.

When results disagree in staging a patient with existing CKD, IRIS similarly recommends repeating the tests in 2 to 4 weeks. If the discrepancy persists, a conservative approach is to assign the patient to the more advanced stage.

Substaging of CKD

After staging, the IRIS Board recommends that dogs and cats be substaged whenever possible on two other important factors:

The amount of protein excreted in the urine
Systemic arterial blood pressure

Both are evaluated because proteinuria and systemic hypertension can occur separately or together at any stage of CKD. Both are also known independent risk factors for progressive kidney injury in human medicine that call for specific treatment, and the same is likely to be true in dogs and cats.

Substaging on Proteinuria

Proteinuria receives special attention because there is good evidence that it is a prognostic indicator in dogs and cats with CKD.

For substaging, the proteinuria must be of renal origin, meaning that pre-renal and post-renal causes have been ruled out first (see our article on proteinuria in dogs and cats). Because persistent proteinuria is more likely to be significant than transient proteinuria, substaging should ideally be based on at least two urine samples collected over a period of at least two weeks. Urine dipsticks can be insensitive, so a quantitative test such as the urine protein-to-creatinine ratio or a species-specific albuminuria test is preferred. Dogs and cats that are persistently borderline proteinuric should be re-evaluated within two months.

The substage is based on the urine protein-to-creatinine ratio (UPC, measured in mass units):

Non-proteinuric: UPC below 0.2 in dogs and cats
Borderline proteinuric: UPC 0.2 to 0.5 in dogs; 0.2 to 0.4 in cats
Proteinuric: UPC above 0.5 in dogs; above 0.4 in cats

For dogs and cats that are proteinuric or borderline proteinuric, the significance of the finding depends on the stage of CKD. The proteinuric substage is generally more significant in Stage 3 than in Stage 1, because the protein load filtered to the tubules falls as the functioning nephron mass declines. A given level of proteinuria therefore becomes more significant as GFR declines.

Substaging on Blood Pressure

Kidney disease can disrupt blood pressure regulation, leading to inappropriately high blood pressure. High blood pressure can damage the kidneys and other target organs, such as the heart (left ventricular hypertrophy), the eyes (bleeding within the eye and hypertensive retinopathy), and the brain (dullness, lethargy, seizures), causing signs and illness outside the kidney.

IRIS therefore recommends that blood pressure be measured in all dogs and cats with CKD. Indirect blood pressure measurement is now widely available in veterinary practice, although several different methods exist and there is no agreed standardized approach. It is important for practitioners to standardize the technique used in their own practice. Our article on hypertension in dogs and cats discusses blood pressure in more detail.

The substage is based on systolic blood pressure and the risk of future target-organ damage:

Normotensive: below 140 mmHg; minimal risk
Prehypertensive: 140 to 159 mmHg; low risk
Hypertensive: 160 to 179 mmHg; moderate risk
Severely hypertensive: 180 mmHg or higher; high risk

Blood pressure substaging depends on the measured pressure and on whether damage to organs outside the kidney is present or threatened. As with proteinuria, persistence should be documented with multiple measurements over time. However, if target-organ damage outside the kidney is already present, persistence does not need to be demonstrated, and treatment should begin immediately. If there is no evidence of such damage, the recommended follow-up depends on the blood pressure substage and the associated risk of damage developing.

Revising the Stage and Substages After Treatment

A patient's stage and substages should be revised as changes occur. For example, if antihypertensive or antiproteinuric treatment has been started, the patient's substage on re-evaluation should reflect its current blood pressure or UPC rather than its original status, with the word "treating" after the relevant substage to show that the current level reflects the effects of treatment. For example, a cat first classified as IRIS CKD Stage 2, borderline proteinuric, severely hypertensive, whose blood pressure and UPC fall on treatment, would be reclassified as Stage 2, non-proteinuric, prehypertensive (treating).

Final Words

The IRIS system allows stable CKD in dogs and cats to be staged on the basis of fasting blood creatinine, blood SDMA, or both, and further characterized by renal proteinuria and systemic blood pressure. The system reflects current knowledge and opinion about CKD in dogs and cats and will continue to evolve as new research and clinical studies are published. Consistent and widespread use of staging should help practitioners with diagnosis and prognosis in CKD, provide a framework for logical treatment plans, and make it easier for veterinarians to communicate about this complex disease.