Kidney disease is the presence of functional or structural abnormalities in one or both kidneys. It is recognized by reduced kidney function or the presence of kidney damage. A decline in function is not essential to meet the definition of kidney disease. Kidney damage is defined as either: 1) microscopic or macroscopic renal pathology detected by kidney biopsy or direct visualization of the kidneys or 2) markers of renal damage detected by blood or urine tests or imaging studies (Table 1).³ Both the severity and clinical implications of kidney disease varies greatly depending on the magnitude of kidney involvement. Kidney disease is staged (described below) to reflect these variations. The term "kidney disease" may be applied to acute or chronic disease.

Table 1. Markers of kidney damage.*

 Blood markers:

  BUN concentration

  Serum creatinine

 Hyperphosphatemia

 Hyperkalemia or hypokalemia

 Metabolic acidosis

 Hypoalbuminemia

 Urine markers:

 Impaired urine concentrating ability

 Proteinuria

 Cylindruria

 Renal hematuria

 Inappropriate urine pH

 Inappropriate urine glucose concentration

 Cystinuria

 Imaging markers--abnormalities in kidney:

 Size

 Density

 Shape

 Number

 Location

 Mineralization

* Markers must be confirmed to be of renal origin to be evidence of kidney damage. For example, hypoalbuminemia due to urinary protein loss is evidence of kidney disease, while hypoalbuminemia due to hepatic failure is not.

Chronic kidney disease (CKD) is defined as: 1) kidney damage that has existed for at least three months, with or without decreased glomerular filtration rate (GFR), or 2) a reduction in GFR by more than 50% from normal persisting for at least three months. A duration of at least 3 months is used as the benchmark criterion for confirming the diagnosis of CKD based on the observation that renal compensatory hypertrophy and improvement in renal function may continue for up to three months following acute loss of nephrons.

Staging CKD

Patients with CKD can be categorized into stages along a continuum of progressive CKD.⁴ The value of staging CKD is to facilitate application of appropriate clinical practice guidelines for diagnosis, prognosis and treatment. The International Renal Interest Society (IRIS) has proposed a 4 tier system for staging CKD in dogs and cats (Tables 2 and 3). Although the specific values used to categorize patients with CKD into these stages are inherently arbitrary, staging is nonetheless useful for establishing prognosis and managing patients with CKD.

Table 2. Stages of CKD in dogs and cats.

Table 3. Classification of proteinuria by UP:C ratio.*

* ACVIM Consensus Statement on Proteinuria (Lees, 2005)

The stage of CKD is assigned based on the level of kidney function. While not the only kidney function, the level of GFR is accepted as the best measure of overall kidney function in health and disease.³ Ideally, two or more serum creatinine values obtained when the patient is fasted and well hydrated should be determined over several weeks to stage CKD. Further, variations between laboratories, patient-specific characteristics (e.g., breed, age, gender, body condition and lean body mass) and transient prerenal and postrenal events may influence serum creatinine values. Reduced muscle mass, a common manifestation of advanced CKD, may result in a substantial reduction in serum creatinine concentration relative to true GFR. Because of these variations, published reference ranges for serum creatinine are often exceedingly broad. Using the IRIS staging system, some patients classified as having CKD stage 2 may have serum creatinine values within published reference ranges. As a consequence, the patient's overall clinical status should be considered when interpreting serum creatinine concentration and other laboratory tests and when planning patient management.

It is important to understand that evidence of CKD should be sought beyond just the serum creatinine value. Just knowing that a dog has a serum creatinine of 2.6 mg/dl does not mean that the dog has Stage III CKD. Creatinine can be used as a marker of kidney disease as discussed previously. True normal values for serum creatinine are usually, but not invariably, quite low (less than 1.4 mg/dl). When creatinine increases above this value, it may be due to renal, prerenal or postrenal causes. It is essential that values above this standard be examined to ascertain which of these causes explains the increase in serum creatinine. Serum creatinine should never be interpreted without consideration of the clinical finding in the patient including examination of the urinalysis (with emphasis on the urine specific gravity). Even though some laboratories report a "normal range" that extends above 1.4 mg/dl, one should question values above 1.4 mg/dl by examining a concurrently collected urine specific gravity. For example, a serum creatinine value above 1.4 mg/dl (in a dog) that is associated with a urine specific gravity of 1.014 implies something entirely different that the same serum creatinine value with a urine specific gravity of 1.039. Values lying between 1.4 mg/dl and the upper limit for a given laboratory would be expected to be associated with relatively concentrated urine to be interpreted as true evidence of normal kidney function (i.e., specific gravity values above 1.03 in dogs and 1.035 in cats).

Stage 1 CKD includes dogs and cats with CKD that are not azotemic, while stage 2 CKD includes dogs and cats that are mildly azotemic (Table 2). Patients in these stages of CKD typically do not have clinical signs of kidney dysfunction with the exception of polyuria and polydipsia. Occasionally cats with stage 2 CKD may have weight loss or selective appetites. However, patients may have clinical signs resulting from their kidney lesions (e.g., acute pyelonephritis, nephrolithiasis). Patients with marked proteinuria or systemic hypertension due to CKD may have clinical signs related to these aspects of CKD. Renal function is often stable or only very slowly progressive for an extended period in non-proteinuric, non-hypertensive dogs and cats with stages 1 and 2 CKD. However, when progression does occur in this group of patients, it may occur largely as a consequence of their primary CKD.⁴ Patients with stages 1 and 2 CKD should be evaluated with the goals of identifying and providing specific treatment for their primary CKD.

Patients with moderate azotemia are classified as stage 3 CKD. Patients in this stage may have clinical signs referable to their loss of kidney function; however, with appropriate treatment, they typically do not have clinical signs of overt uremia.

Patients with stage 3 CKD may progress due to inherent mechanisms of spontaneous progression as well as their underlying CKD. Therefore, in addition to identifying and treating primary CKD, therapy designed to modify factors promoting progression of renal disease may be of benefit to these patients.

Stage 4 CKD includes dogs and cats with severe azotemia (serum creatinine values greater than 5.0 mg/dl). This stage is also called chronic kidney failure and is frequently associated with clinical signs that occur as a consequence of loss of kidney function. Diagnostic and therapeutic initiatives in this stage include those appropriate for stage 3 patients as well as therapy designed to prevent or ameliorate signs of uremia.

It is useful therapeutically and prognostically to further subclassify patients according to their urine protein loss and systemic blood pressure. Proteinuria and hypertension may influence prognosis and may be amenable to therapeutic intervention. Classification of patients as proteinuric necessitates eliminating hemorrhage and/or inflammation as the cause for proteinuria and determination of the urine protein-to-creatinine ratio. Further, proteinuria should be shown to be persistent by reexamining the UPC ratio 2 to 3 times over at least one or two months. For both dogs and cats, patients are classified as proteinuric (P) when their protein-to-creatinine ratio exceeds 0.5 and 0.4, respectively (Table 4). Patients with borderline proteinuria should be re-evaluated after two months to reassess classification. In some patients, classification of proteinuria may change due to the natural course of their disease or in response to therapy.

Table 4. Blood pressure risk groups for dogs and cats.

The lack of consensus as to what blood pressure values constitute hypertension in dogs and cats obfuscates any classification of patients as to their hypertension status. It is likely that "normal" blood pressure values for dogs and cats will change as more data becomes available. A 2003 ACVIM Hypertension Consensus Group has proposed the following hypertension classification system for dogs and cats. The same system is advocated by IRIS.