Reassessment of "Normal" Values in Dogs and Cats With Chronic Kidney Disease

Adapted from the IRIS education article by Gregory F. Grauer, Kansas State University. The staging values, blood pressure categories, treatment recommendations, and phosphorus targets below have been updated to the IRIS guidelines as modified in 2026.

Introduction

Chronic kidney disease (CKD) is a major cause of illness and death in dogs and cats. The prevalence of CKD has been estimated at 0.5% to 1.0% in dogs and 1.0% to 3.0% in cats (references 1 and 2), but it increases with age, especially in cats. It has been estimated that as many as 30% to 50% of cats aged 15 years or older have CKD (references 3 to 5).

The nephron damage associated with CKD is usually irreversible and often progressive. In dogs, in which proteinuric kidney disease is more common, the progressive loss of kidney function tends to be common, steady, and relatively rapid compared with cats. Cats may have stable kidney function for months to years and be relatively unaffected by CKD, or they may have slowly progressive disease over several years. Animals may also be stable for a long time and then have an abrupt, unpredictable decline in kidney function. Soft tissue mineralization, systemic hypertension, intraglomerular hypertension, and proteinuria have all been associated with the progression of CKD.

Although it is not possible to improve kidney function in CKD, it is logical to assume that early diagnosis could improve clinical outcomes for dogs and cats. There is firm evidence for dietary treatment, and increasing evidence that anti-proteinuric treatments can slow the progression of azotemic CKD.

Early Diagnosis of CKD: Blood Creatinine

Early, non-azotemic CKD (IRIS Stage 1) can be diagnosed in dogs and cats with abnormal kidney palpation or imaging findings, persistent renal proteinuria, or a urine concentrating deficit caused by kidney disease. In most cases, however, CKD is diagnosed on the basis of persistent azotemia together with an inability to concentrate urine adequately, although some cats with CKD keep the ability to concentrate their urine.

Blood creatinine is the most commonly used marker of glomerular filtration rate (GFR) in dogs and cats. Creatinine is produced by the non-enzymatic breakdown of creatine and creatine phosphate in skeletal muscle, so serum creatinine reflects the patient's muscle mass as well as GFR. Blood creatinine can also be influenced by the method of analysis (the Jaffé reaction versus enzymatic methods, and bench-top analyzers versus reference laboratories). One of the most troubling aspects of interpreting blood creatinine is the relatively large variation in reference intervals between laboratories, which can lead to false-positive and false-negative diagnoses of azotemia (references 6 and 7). Reference ranges need to be specific to each laboratory, but many veterinary nephrologists have suggested that renal azotemia may begin at blood creatinine concentrations lower than the upper limit of most reference ranges, that is, at 1.4 mg/dL in dogs and 1.6 mg/dL in cats (reference 8).

Blood Creatinine and the IRIS CKD Stages

  • Stage 1, non-azotemic CKD: below 1.4 mg/dL in dogs; below 1.6 mg/dL in cats
  • Stage 2, mild renal azotemia: 1.4 to 2.8 mg/dL in dogs; 1.6 to 2.8 mg/dL in cats
  • Stage 3, moderate renal azotemia: 2.9 to 5.0 mg/dL in dogs and cats
  • Stage 4, severe renal azotemia: above 5.0 mg/dL in dogs and cats

Blood creatinine must always be interpreted in light of the patient's muscle mass, urine specific gravity, and physical examination findings, to rule out pre-renal and post-renal causes of azotemia. Dogs vary greatly in muscle mass, from a miniature poodle to a greyhound, which tends to widen reference ranges (reference 9). This makes blood creatinine an insensitive marker of reduced kidney function in some breeds when it is interpreted simply as inside or outside the reference interval.

Despite these confounding factors, following blood creatinine over time, measured by a consistent method, is an excellent way to assess kidney function and diagnose early CKD. For example, a blood creatinine that rises from 0.6 to 1.2 mg/dL over several years, without evidence of dehydration or an increase in muscle mass, could indicate at least a 50% reduction in GFR, even though the creatinine is still within the reference range. Because blood creatinine is inversely related to GFR, a doubling of creatinine corresponds to roughly halving of the GFR. In this example, the actual loss of nephrons is likely to exceed 50%, because compensatory hypertrophy increases the functional capacity of the remaining nephrons.

Early Diagnosis of CKD: SDMA

Serum symmetric dimethylarginine (SDMA) is formed by the methylation of L-arginine within cell nuclei by protein-arginine methyltransferases and is released into the circulation when proteins are broken down. SDMA is eliminated mainly by the kidneys and is a biomarker for diagnosing and monitoring CKD (references 10 and 11). In two longitudinal studies, one in dogs and one in cats that developed CKD, SDMA rose above normal before blood creatinine rose above the reference range (above 1.8 mg/dL in dogs and above 2.1 mg/dL in cats): on average about 17 months earlier in cats and about 9 months earlier in dogs (references 10 and 12). Interestingly, if a creatinine above 1.6 mg/dL had been considered abnormal in the feline study, creatinine and SDMA would have identified renal azotemia in these cats at nearly the same time (reference 10).

An SDMA above 14 µg/dL, and especially above 20 µg/dL, can support an early diagnosis of CKD when there are other abnormalities, such as abnormal kidney palpation or imaging findings, persistent renal proteinuria, or a urine concentrating deficit. If an increased SDMA is the only abnormality, it may suggest CKD, but the increase should persist for at least 2 to 3 months.

Early Diagnosis of CKD: Urine Protein-to-Creatinine Ratio

Proteinuria in dogs and cats with CKD can result from glomerular lesions, tubular lesions, or both. Glomerular proteinuria can be caused by loss of integrity of, or damage to, the capillary wall, as in immune-complex disease and X-linked hereditary nephropathy. Increased pressure in the glomerular capillaries probably also increases the amount of plasma protein filtered. This intraglomerular hypertension may result from the loss of nephrons, which impairs autoregulation, and from systemic hypertension being transmitted into the glomerular capillaries. Structural glomerular disease and CKD are often accompanied by systemic hypertension, which can worsen intraglomerular hypertension and glomerular proteinuria.

Tubular proteinuria occurs when the tubules cannot reabsorb protein from the glomerular filtrate normally, and it is typically less severe than glomerular proteinuria. In dogs and cats with CKD, tubular reabsorption of protein can be reduced by tubulointerstitial injury and a decrease in the number of functioning tubules. Whether it is caused by capillary wall lesions, tubular lesions, or intraglomerular hypertension, excessive protein in the glomerular filtrate may contribute to further glomerular and tubulointerstitial lesions and the loss of more nephrons. Proteinuric kidney disease and systemic hypertension often coexist, so it can be difficult to separate the effects of high systemic and intraglomerular pressures from those of proteinuria.

Renal proteinuria in dogs and cats with CKD should be diagnosed step by step:

  1. Confirm it. In health and in disease, albumin is the main protein in the urine of dogs and cats. The specificity of the dipstick screening test for albuminuria is poor, especially in cats, so a positive dipstick should be confirmed with a more specific test, such as the sulfosalicylic acid turbidimetric test, the urine protein-to-creatinine ratio (UPC), or a species-specific albuminuria assay.
  2. Determine its origin. Physiological or benign proteinuria, and pre-renal and post-renal proteinuria, must be ruled out. Renal proteinuria is persistent and is associated with an inactive urine sediment, although hyaline casts may be seen. Persistent proteinuria is defined as at least two positive tests two weeks apart.
  3. Quantify and monitor it. Once persistent renal proteinuria has been documented, it should be quantified, if this has not already been done, by measuring the UPC, which is used to guide and monitor treatment. Serial UPC measurements show whether the proteinuria is stable, increasing, or decreasing over time.

IRIS Classification of Renal Proteinuria in Dogs and Cats

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

The IRIS treatment recommendations advise that persistent proteinuria of renal origin with a UPC above 0.4 in cats or above 0.5 in dogs be investigated and treated at any stage of CKD, including non-azotemic Stage 1. Cats are treated with a kidney diet and an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). Dogs are treated with a kidney diet and an ARB, and an ACEI is added only cautiously if the proteinuria is not controlled. Borderline proteinuria (UPC 0.2 to 0.5 in dogs, or 0.2 to 0.4 in cats) warrants closer monitoring, and in cats with persistent borderline proteinuria, treatment may be offered. Note that borderline and even "normal" levels of proteinuria in cats have been associated with progressive disease.

For example, in cats with naturally occurring CKD, relatively mild proteinuria (UPC 0.2 to 0.4) increased the risk of death or euthanasia 2.9-fold compared with cats with a UPC below 0.2 (reference 13). In a prospective longitudinal study of non-azotemic cats older than 9 years, 95 cats (median age 13 years) were followed for 12 months or until death or the development of azotemia, defined as a blood creatinine above 2.0 mg/dL. Twenty-nine of the 95 cats (30.5%) developed azotemia, and proteinuria at presentation (median UPC 0.19 versus 0.14) was significantly associated with the development of azotemia in these older cats (reference 14). Finally, when client-owned cats with stable CKD (112 cats) were compared with client-owned cats with progressive CKD (101 cats), the median UPC was higher in the progressive group (0.27 versus 0.14), and each 0.1 increase in UPC was associated with a 24% increase in the risk of CKD progression (reference 15).

These observational studies suggest that the relationship between proteinuria at diagnosis and both death from any cause and the risk of CKD progression is continuous. Prospective intervention studies are needed to:

  1. Redefine the proteinuria classification in terms of the level of proteinuria that should trigger treatment
  2. Determine the post-treatment UPC target that indicates successful treatment
  3. Determine which treatments improve survival and slow progression in dogs and cats through such a reduction in proteinuria

Management of CKD: Systolic Blood Pressure

Current recommendations are that blood pressure be measured in a quiet area before the patient is examined, typically with the owner present, after 5 to 10 minutes of acclimation. The American College of Veterinary Internal Medicine (ACVIM) hypertension guidelines suggest discarding the first measurement and then obtaining at least 3, and preferably 5 to 7, consecutive measurements that vary by less than 10% to 20% in systolic pressure (reference 16). The animal's demeanor, body position, and heart rate, the cuff size and measurement site, and all measured values should be recorded in the medical record. Hypertension should be documented more than once before the diagnosis is accepted and treatment is started, unless it is accompanied by target organ damage, such as eye lesions.

IRIS Classification of Systolic Blood Pressure in Dogs and Cats

  • Normotensive: below 140 mmHg, minimal risk of target organ damage
  • Prehypertensive: 140 to 159 mmHg, low risk
  • Hypertensive: 160 to 179 mmHg, moderate risk
  • Severely hypertensive: 180 mmHg or higher, high risk

IRIS blood pressure substaging for dogs and cats with CKD is based on the risk of damage to target organs: the eyes, the nervous system, the heart, and the kidneys. Not long ago, indirect systolic blood pressure measurements above 170 to 180 mmHg were considered the threshold for hypertension. Despite the inherent difficulties of indirect blood pressure measurement in dogs and cats, it is now considered appropriate to regard systolic hypertension as present at lower pressures, from 160 mmHg. It is important to keep in mind, however, that lowering treatment thresholds reduces specificity and could result in dogs and cats being treated without need or benefit.

In one study, 45 dogs with naturally occurring CKD were divided into three groups by initial systolic blood pressure and followed for up to 2 years: high (161 to 201 mmHg, 14 dogs), intermediate (144 to 160 mmHg, 15 dogs), and low (107 to 143 mmHg, 16 dogs). The high blood pressure group had an increased risk of uremic crisis and death compared with the low blood pressure group, with a median survival of less than 200 days versus more than 400 days (reference 17).

In cats with an experimental remnant kidney-wrap model of CKD, systolic hypertension (mean pressure 168 versus 113 mmHg) was associated with reduced GFR (1.34 versus 3.55 mL/min/kg), increased UPC (1.2 versus 0.1), and increased glomerulosclerosis (reference 18). Similarly, in dogs with the remnant kidney-wrap model of CKD, systolic hypertension (above 160 mmHg) was associated with reduced GFR, an increased UPC, and increased mesangial matrix accumulation, tubular lesions, fibrosis, and cellular infiltrates (reference 19). Cats with progressive CKD had higher systolic blood pressure than cats with stable CKD (155 versus 147 mmHg) (reference 15). Finally, in 69 cats with naturally occurring CKD, a high time-averaged systolic blood pressure (159 versus 136 mmHg) was correlated with glomerulosclerosis and hyperplastic arteriolosclerosis (reference 20). Together, these findings support the view that blood pressure below the hypertensive cut-off of 160 mmHg, in the prehypertensive range of 140 to 159 mmHg, may contribute to kidney injury in some animals. In people with hypertension who are also proteinuric, for example, treatment targets tend to be lower (reference 21).

Management of CKD: Serum Phosphorus

As with blood creatinine, serum phosphorus reference ranges vary between laboratories. This variability is probably due at least in part to the higher serum phosphorus concentrations of healthy, young, growing puppies and kittens. Soft tissue mineralization of the kidney causes irreversible nephron damage and is associated with CKD progression in dogs and cats.

Cats with stable CKD had lower serum phosphorus concentrations than cats with progressive CKD (4.4 versus 5.1 mg/dL), and serum phosphorus predicts CKD progression in cats, with a 41% increase in the risk of progression for every 1.0 mg/dL increase in serum phosphorus (reference 15). In 80 client-owned cats with CKD, serum phosphorus concentrations were correlated with renal interstitial fibrosis (reference 20). In dogs with CKD, a serum calcium-times-phosphorus product above 70 mg²/dL² was a poor prognostic indicator (reference 22). These findings have prompted closer scrutiny of the therapeutic targets for serum phosphorus in dogs and cats with CKD. The current IRIS treatment recommendations suggest the following targets, which are typically well within laboratory reference ranges (reference 8).

IRIS Targets for Serum Phosphorus in Dogs and Cats With CKD

  • Stage 2: 2.7 to 4.6 mg/dL in dogs and 2.7 to 4.5 mg/dL in cats (0.9 to 1.5 mmol/L). A kidney diet, adding an intestinal phosphate binder if the target is not reached.
  • Stage 3: 2.7 to 5.0 mg/dL (0.9 to 1.6 mmol/L). A kidney diet, with an intestinal phosphate binder if needed.
  • Stage 4: 2.7 to 6.0 mg/dL (0.9 to 1.9 mmol/L). A kidney diet with an intestinal phosphate binder.

In cats whose phosphorus is already within the target range, IRIS suggests that a blood FGF-23 concentration above 400 pg/mL, without high calcium, anemia, or marked inflammatory disease, is a reason to start dietary phosphate restriction (see our article reviewing the role of FGF-23).

Summary

  • Laboratory reference ranges are wide, and CKD can be present while blood creatinine, SDMA, and UPC are still "normal." Following an individual patient's values over time is more sensitive than comparing a single value with a reference range.
  • A creatinine persistently above 1.4 mg/dL in a dog or 1.6 mg/dL in a cat, or a persistently increased SDMA, deserves investigation and closer monitoring.
  • In cats, even borderline or high-normal proteinuria is associated with a greater risk of developing azotemia and of CKD progression.
  • Blood pressure in the prehypertensive range of 140 to 159 mmHg may contribute to kidney injury in some animals, and blood pressure should be measured carefully and repeatedly.
  • IRIS phosphorus targets in CKD are lower than the upper limit of most laboratory reference ranges, because higher phosphorus is associated with kidney mineralization, fibrosis, and progression.

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