Education

IRIS CKD Guidelines Updates 2014 - 2015
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The IRIS Board made three significant changes to CKD Guidelines during 2014 and 2015. A summary of these new recommendations is presented here. The full version of 2015 Guidelines will be uploaded during our website relaunch by the end of 2015.

Substaging by Arterial Blood Pressure

We recommend replacement of the existing abbreviations for blood pressure substages (AP0-AP1) with descriptive terms as follows:

Systolic blood pressure
(mm Hg)
Diastolic blood pressure
(mm Hg)
Risk of future target organ
damage
BP substage
OriginalNew
<150 <95 Minimal AP0 Normotension
150 - 159 95 - 99 Mild AP1 Borderline hypertension
160 - 179 100 - 119 Moderate AP2 Hypertension
>180 >120 Severe AP3 Severe hypertension

Treatment of Proteinuria

We recommend that IRIS CKD Stage 1 patients with persistent proteinuria (UPC ≥ 0.5 for dogs or 0.4 for cats) are not only monitored and thoroughly investigated but also receive standard treatment for proteinuria as currently recommended for IRIS CKD Stages 2 to 4. This parallels the IRIS consensus statement on standard treatment for glomerulonephritis (J Vet Intern Med 2013;27:S27–S43).

Interpreting Blood Concentrations of Symmetric Dimethylarginine (SDMA) in CKD

SDMA concentrations in blood (plasma or serum) may be a more sensitive biomarker of renal function than blood creatinine concentrations. 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.

IRIS Staging System

Overview of the IRIS staging system for CKD (revised 2016)

J Elliott, London, UK and ADJ Watson, Sydney, Australia

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, intended to facilitate communication about the diagnosis and management of this complex syndrome amongst veterinary practitioners and students. The IRIS group currently has 15 Board members from 11 countries around the world. The staging system first devised was used subsequently by IRIS Board members, refined on the basis of such use, and then further modified in the light of feedback from the American and European Societies of Veterinary Nephrology and Urology.

A staging system for defining heart failure in veterinary medicine, based on one used in human medicine, has been in use for some years. The IRIS system for staging CKD also follows a scheme used in human medicine. The IRIS Board has recently reviewed the system in light of recent publications relating to new biomarkers of kidney disease. The present IRIS CKD staging process should always be viewed as a work in progress that will continue to be modified progressively as experience using the current staging system accumulates and additional information becomes available. It is therefore important when staging to ensure that you use the most recently updated version of the system, which will normally be found on the IRIS website (www.iris-kidney.com).

It is hoped that widespread application of this staging system, and reporting of accurately staged case series, including treatments and outcomes, will enhance our overall understanding of the natural history of canine and feline CKD patients, and help identify better approaches to its management.

From the point of view of the individual practitioner, consistent and accurate use of IRIS staging should help provide useful prognostic information and identify the likely consequences of the CKD that will require management at the different stages of dysfunction.

The challenge for all of us is to find ways to recognize kidney diseases earlier in their course, before clinical signs are evident, to permit institution of any available measures (prevention, treatment or monitoring) that might slow progression of the disease and prevent development of complications. This is why novel early biomarkers of CKD are actively being researched and this is reflected in recent updates to the staging system.

Selecting dogs and cats to be staged

It must be emphasized that the IRIS staging system is only applicable to dogs and cats with stable CKD. Staging is not appropriate in animals with abnormal renal function in which the blood creatinine concentration changes dramatically over a short period of time.

So therefore, when investigating azotaemia, one must determine initially whether the cause is:

  1. pre-renal,
  2. primary intrinsic renal, or
  3. post-renal.

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

  1. acute,
  2. decompensated chronic (sometimes termed 'acute on chronic'), or
  3. chronic.

Again, remember only stable CKD is appropriate for staging using the proposed method. However, if the patient has acute kidney injury (or decompensated CKD) it is possible that it could stabilize into chronic CKD after 4 to 12 weeks of management, at which point staging could be undertaken. Prior to that, the rapidly changing state of the patient and acuteness of the situation means the IRIS AKI grading system should be applied here and those categorised as pre-renal (or volume responsive AKI) and post-renal azotaemia identified so that appropriate frequent monitoring and adjustments to treatment are applied to protect their kidneys from acutely progressive damage if possible (see AKI grading system article).

Staging on blood creatinine concentration

The primary factor for staging CKD is the concentration of creatinine in plasma or serum, because this is presently the most useful and widely available test of kidney function in veterinary practice. For proper interpretation, the patient must be fasting and well hydrated at the time blood is sampled.

The blood creatinine concentrations used to define IRIS CKD Stages 1 to 4 (details shown within theIRIS Guidelines) were reached by debate and consensus, based on clinical experience of the Board members and data derived from longitudinal studies. As noted previously, they and other elements of staging may be modified in future as more knowledge is gained.

The first two stages of the system reflect the fact that a large proportion of kidney tissue has to be damaged before a rise in blood creatinine concentration is detectable. Hence Stage 1 and early Stage 2 encompass creatinine concentrations that are within or overlap the reference ranges for most laboratories. So, for an animal to be classified in Stage 1, for example, some other abnormality must be detected to create the suspicion that a disease is present in kidney tissue. This could include:

  1. inadequate urinary concentrating ability in the absence of an identifiable extra-renal cause,
  2. detection of renal proteinuria,
  3. abnormal size or shape of the kidneys on palpation, confirmed by diagnostic imaging,
  4. abnormal kidney biopsy findings, or
  5. increasing creatinine concentrations (even if they remaining within the laboratory reference range) on serial sampling.
  6. blood symmetric dimethylarginine concentration above 14 g/dl

Some animals with CKD pass through all four stages if their kidney disease progresses, but some animals will remain stable within one stage and die of another disease before kidney disease has progressed. Affected animals may be presented to the veterinarian at any stage, depending on how observant their owner is and whether routine, regular health screening is being practised.

In future iterations of the IRIS CKD staging system it is possible that staging will be based on an adjusted blood creatinine concentration that takes into account the body condition score or muscle mass. This is because muscle mass governs the rate of endogenous production of creatinine. Several formulae that include various other factors are used presently in human medicine but to date none have proved sufficiently useful to be recommended for veterinary use. A new surrogate marker of glomerular filtration rate (symmetric dimethylarginine, SDMA)) shows promise primarily because its production rate is not dependent on muscle mass, it being a breakdown product of methylated proteins throughout the body (see educational article on SDMA). SDMA measurement is specialised and standardisation between laboratories is required before recommendations can be generalised to all laboratories measuring this analyte. The published literature which has informed the inclusion of SDMA within the IRIS CKD staging guidelines is based on the assay offered by Idexx Laboratories Ltd. These recommendations are preliminary and may be modified as the veterinary profession gains more experience of the use of this marker.

Another possibility is that measurement of glomerular filtration rate (GFR) by a plasma clearance method will come to replace blood creatinine concentration as the major criterion for IRIS CKD staging; this development awaits identification and acceptance of suitable practical methods for measuring GFR in general veterinary practice. The most promising test currently available through a few specialist laboratories is the iohexol plasma clearance test. Plasma clearance methods will always be more involved and less convenient to use than surrogate markers of GFR, such as blood creatinine concentrations, despite the limitations of the latter.

Substaging of CKD

Following staging based on blood creatinine concentration, the IRIS Board recommends that patients be substaged whenever possible based on two other important factors:

  1. the quantity of protein excreted in urine, and
  2. systemic arterial blood pressure.

Evaluation of these two variables is recommended because proteinuria and systemic arterial hypertension can occur separately or together at any stage of CKD. In addition, both are known independent risk factors for progressive renal injury in human medicine that warrant specific treatment protocols; the same is likely to be true for veterinary patients.

Substaging on proteinuria

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

For substaging on proteinuria, the proteinuria must be of renal origin: that is, pre-renal and post-renal causes have to be ruled out first (see the education article on proteinuria on this website). As persistent proteinuria is considered more likely to be significant than transient proteinuria, the substaging ideally should require persistence of proteinuria to be demonstrated in three or more urine samples collected over at least a two-week period.

The substage classification as non-proteinuric, borderline proteinuric, or proteinuric is based on the urine protein to creatinine ratio (UP/C, determined using mass units). The UP/C cut-offs defining these substages are presented at the IRIS Guidelines section in IRIS Staging of CKD.

For animals found to be proteinuric or borderline proteinuric, the significance of the finding depends on the concurrent stage of CKD. Thus, the proteinuric substage is more significant at Stage 3 than at Stage 1; this is because the filtered protein load presented to tubules reduces as the functioning nephron mass declines. Consequently, a given level of proteinuria attains higher significance as GFR declines.

Substaging on systemic arterial blood pressure

Kidney disease can affect blood pressure regulation leading to inappropriately high blood pressure. High blood pressure can be damaging to the kidneys and can also damage other target organs such as the heart (left ventricular hypertrophy), the eye (hyphaema, hypertensive retinopathy) and the brain (dullness, lethargy, seizures) leading to extra-renal signs and morbidity.

The IRIS group therefore recommends that arterial blood pressure should be measured in all patients with CKD. The wider availability of indirect blood pressure measurement in veterinary practice means this variable can be assessed more readily now, although there are presently several different methods and no agreed standardized approach. However, it is important for practitioners to standardize the techniques they use in their practice. Further discussion on blood pressure can be found in an associated education item onhypertensionon this website.

Blood pressure substaging is based on the measured arterial pressure and whether extra-renal target-organ damage is present or threatens. As with proteinuria, documentation of persistence should be based on multiple sequential blood pressure measurements. On the other hand, if extra-renal target-organ damage is already present, demonstration of persistence is not necessary and treatment should begin immediately.

If no evidence of extra-renal target-organ damage is recognized, the recommended follow-up depends on the blood pressure stage and the associated perceived risk of development of such changes, as detailed in the associated article on blood pressure.

Revision of staging and substaging after therapy

The stage and substages assigned to the patient should be revised appropriately as changes occur. For example, if antihypertensive (or antiproteinuric) therapy has been instituted, the patient's designation on re-evaluation should reflect the current blood pressure (or UP/C) rather than the original status, with an additional sign (T) after the relevant substage indicator to show that the current level reflects treatment effects.

Final words

The IRIS system allows CKD in dogs and cats to be staged on the basis of the fasting blood creatinine concentration and further characterized according to renal proteinuria and systemic arterial blood pressure. The system reflects current knowledge and opinion about CKD in dogs and cats and will continue to evolve as the results of new research and clinical studies are published. Consistent and widespread use of staging should aid practitioners with diagnosis and prognosis in CKD, provide a framework for logical treatment plans, and facilitate communication between veterinarians about this complex disease syndrome.

Further reading

Elliott, J. (2007) Staging chronic kidney disease. In "BSAVA Manual of Canine and Feline Nephrology and Urology" 2nd edn, eds J Elliott and GF Grauer.

Elliott, J and Watson, ADJ (2009) Chronic kidney disease: staging and management. In "Kirk's Current Veterinary Therapy XIV", eds JD Bonagura and DC Twedt.

Elliott, J and Watson, ADJ (2014) Chronic kidney disease: IRIS staging and management. In "Kirk's Current Veterinary Therapy XV", eds JD Bonagura and DC Twedt.