Jonathan Elliott, London, UK, and ADJ Watson, Sydney, Australia
The International Renal Interest Society (IRIS) was formed in 1998. One 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 14 Board members from 10 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 present IRIS staging process should be viewed as a work in progress that will be modified progressively as 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.
In the longer term, the challenge for all of us is to find ways to recognize kidney diseases earlierin 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 avoid development of complications.
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 other forms of disease affectingdisorders affecting kidney function, where the blood creatinine concentration can change dramatically over a short period of time.
SoTherefore, whenin investigating azotaemia, one must determine initially whether the cause is:
primary intrinsic renal, or
Then, if the cause is primary intrinsic kidney disease, determine whether the kidney disease is:
decompensated chronic (sometimes termed ‘acute on chronic’), or
Again, remember only stable CKD can be staged accurately by the proposed method. However, if the patients has acute kidney disease or decompensated CKD it is possible that it could stabilize into chronic CKD after 4 to 8 weeks of management, at which point staging could be undertaken.
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 readily 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 Stages I to IV (detailed shown elsewhere on the IRIS webpage) 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 I and early Stage II encompass creatinine concentrations that are within or overlap the reference ranges for most laboratories. So, for an animal to be classified in Stage I, for example, some other abnormality must be detected to create the suspicion that a disease is present in kidney tissue. This could include:
inadequate urinary concentrating ability in the absence of an identifiable extra-renal cause,,
detection of renal proteinuria,,
abnormal size or shape of the kidneys on palpation, confirmed by diagnostic imaging,,
abnormal kidney biopsy findings, or
increasing creatinine concentrations (even if they remaining within the laboratory reference range) on serial sampling.
It is likely that 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 their kidney disease has had a chance to progress. 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 practiced.
In future iterations of the staging IRIS 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 and are currently under investigation for veterinary patients.
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 staging; this development awaits identification and acceptance of suitable practical methods for measuring GFR in general veterinary practice.
Substaging of CKD
Following staging on the basis of blood creatinine concentration, the IRIS group recommends for that casepatients to be substaged whenever possible on two other important factors:
the quantity of protein excreted in urine, and
systemic arterial blood pressure.
Evaluation of these two variables is advisable recommended because each can occur separately or together at any stage of CKD, and because 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 in for veterinary medicinepaatients.
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. 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 over at least a two-week 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 elsewhere on this webpage.
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 III than at Stage I; 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 on this webpage.
Blood pressure substaging is based on the measured arterial pressure and whether extra-renal end organ damage is present or threatens. As with proteinuria, documentation of persistence of risk should be based on multiple sequential blood pressure measurements. On the other hand, if extra-renal end-organ damage is already present, demonstration of persistence is not necessary and treatment should begin immediately.
If no evidence of extra-renal end organ damage is recognized, the recommended follow-up depends on the 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.
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 urine protein content and systemicarterial 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.
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