Chronic Kidney Disease

International Renal Interest Society Staging and Management

Jonathan Elliott, London, United Kingdom

The International Renal Interest Society (IRIS) has developed a staging system for chronic kidney disease (CKD) in cats and dogs that aims to improve communication about diagnosis and management of this complex syndrome. The IRIS CKD Staging system is considered a work in progress, to be reviewed and modified at least annually as additional information becomes available; the most recent version can be accessed at www.iris-kidney.com. Since its inception, the staging system has gained increasing acceptance among veterinary nephrologists and clinicians. Publications have now appeared that use this approach to report accurately staged case series, together with treatments and outcomes that improve our overall understanding of the natural history of CKD in cats and dogs and help identify better approaches to management (Cortadellas et al, 2010; Hsu et al, 2011). Consistent and accurate use of IRIS staging of CKD should help individual practitioners provide prognostic information and identify the likely consequences that require monitoring and management at the different stages of dysfunction.

Diagnosis of Chronic Kidney Disease

When faced with an animal suspected of having CKD, practitioners should adopt a logical approach to diagnosis. The recommended minimum set of data to be obtained for such patients is shown in Box 189-1. The historical and physical abnormalities that led to this suspicion should be reviewed because these findings and other evidence may highlight specific problems that warrant further investigation to determine the type of kidney disease present. This review also may indicate whether an underlying cause is likely to be identified by further investigations and whether concomitant diseases should be suspected.

Box 189-1 Minimal Data Set for Patients Suspected of Having Kidney Disease

^*If possible, urinalysis should include estimation of the ratio of urine protein to creatinine for both cats and dogs.

Laboratory evaluation should include appropriate blood biochemical tests, hematologic studies, and complete urinalysis. The results of these tests should confirm the clinical diagnosis but also may give indications of the causes and the possible presence of underlying diseases. Because kidney disease increases in prevalence as cats and dogs age, the practice of performing geriatric screening tests to detect kidney dysfunction has become more widespread. The IRIS minimum recommended geriatric screening tests for this purpose, together with a more ideal complete version, are presented in Box 189-2.

Box 189-2 Geriatric Screening Tests (for Cats and Dogs Older than 6 Years)

• Complete hematologic studies

• Full biochemical panel

• Complete urinalysis

Selection of Cats and Dogs for Staging

It must be emphasized that the IRIS CKD Staging system is applicable only to cats and dogs with stable CKD—it is not appropriate for other disorders affecting kidney function in which blood creatinine concentrations can change dramatically over a short period of time. Therefore it is important to ensure that primary intrinsic kidney disease is present and that any prerenal and postrenal contributions to azotemia have been eliminated before CKD is staged in a patient. If the patient has acute kidney injury or decompensated chronic disease (also known as acute on chronic disease), it is possible that the condition will stabilize into CKD after 4 to 8 weeks of management, at which time IRIS CKD Staging can be considered.

Staging Based on Blood Creatinine Concentration

The primary indicator for IRIS staging of CKD is the concentration of creatinine in plasma or serum because currently this is the most useful and readily available test of kidney function in veterinary practice. 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 shown in Table 189-1 were reached by debate and consensus based on the clinical experiences of veterinary nephrologists and data derived from longitudinal studies. As noted previously, they and other elements of staging may be modified in the future as more knowledge is gained.

TABLE 189-1

IRIS CKD Staging Based on Blood Creatinine Concentration

Stage	Creatinine (mg/dl [µmol/L])*	Comments
At risk	As for Stage 1	History suggests the animal is at increased risk of developing CKD in the future because of a number of factors (e.g., exposure to nephrotoxic drugs, breed, high prevalence of infectious disease in the area, or old age).
1	<1.4 (125) dogs <1.6 (140) cats	Nonazotemic. Some other renal abnormality present (e.g., 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	1.4-2 (125-180) dogs 1.6-2.8 (140-250) cats	Mild renal azotemia (lower end of the range lies 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	2.1-5 (181-440) dogs 2.9-5 (251-440) cats	Moderate renal azotemia. Many extrarenal clinical signs may be present.
4	>5 (>440) dogs and cats	Severe renal azotemia. Many extrarenal clinical signs usually are present.

IRIS, International Renal Interest Society; CKD, chronic kidney disease.

^*Note that these blood creatinine concentrations apply to dogs of average size; for those of extreme size (e.g., miniature and giant breeds) these ranges may not be appropriate.

The IRIS board now proposes an “at-risk” stage of CKD to identify patients that, because of their history (e.g., exposure to nephrotoxic drugs), breed (in which familial kidney disease is common), or geographic location and lifestyle (e.g., residence in an area where leishmaniasis is very common) warrant close monitoring of kidney function. These patients differ from those with IRIS CKD Stage 1 in that they have no laboratory or physical abnormality at the time of examination. The first two numbered 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 IRIS CKD Stage 1 and early Stage 2 encompass creatinine concentrations that are within or overlap the reference ranges for most laboratories.

It is likely that some animals with CKD pass through all four IRIS stages if their kidney disease progresses. But some animals remain in stable condition within one stage and die of another disease before kidney disease has a chance to progress. Affected animals may be brought to the veterinarian at any stage, depending on how observant the owner is and whether routine regular health screening is being practiced.

Substaging of Chronic Kidney Disease

Following staging, it is recommended that substaging be performed using the quantity of protein excreted in the urine and the systemic arterial blood pressure. Evaluation of these two variables is warranted because abnormalities in each can occur separately or together at any stage of CKD. Moreover, increases in both are known independent risk factors for progressive renal injury in human medicine that warrant specific treatment; the same is likely to be true in veterinary patients.

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 IRIS CKD substaging based on proteinuria to be used, the proteinuria must be of renal origin; therefore prerenal and postrenal causes of proteinuria have to be ruled out first. Because persistent proteinuria is considered more likely to be significant than transient proteinuria, substaging ideally requires proteinuria to be demonstrated in three or more urine samples over at least a 2-week period. It is important that urine sediment be examined microscopically on each occasion to rule out the presence of inflammation in the urinary tract (see Chapter 187). The three substages are nonproteinuric (NP), borderline proteinuric (BP), and proteinuric (P), based on the urine protein/creatinine (UP/C) ratio (determined using mass units), as shown in Table 189-2. Note that UP/C ratios classified as NP or BP may be categorized as microalbuminuric when other test methods are used. Because the significance of microalbuminuria in predicting future renal health is not understood at present, the current IRIS recommendation is to continue monitoring these patients for proteinuria using UP/C determinations. For animals found to have P or BP disease, the significance of the finding depends on the concurrent stage of CKD. Thus the P 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 has higher significance as glomerular filtration rate (GFR) declines. Note that UP/C ratios at the BP or P level can indicate tubular or glomerular dysfunction, but once the UP/C ratio exceeds 2.0 it most likely indicates a primary glomerular problem. Response to any treatment given to reduce proteinuria (see later) should be monitored at appropriate intervals using the UP/C ratio.

TABLE 189-2

IRIS CKD Substaging by Urine Protein/Creatinine (UP/C) Ratio