Understanding Creatinine Levels in Dogs

Adapted from the IRIS education article "Interpreting blood creatinine concentration in dogs" by HP Lefebvre (Toulouse, France), ADJ Watson (Sydney, Australia) and R Heiene (Oslo, Norway), revised 2022. The previous version was written by HP Lefebvre and ADJ Watson (2015).

Where Does Creatinine Come From?

Creatinine is produced in the body by an irreversible, non-enzymatic process. This happens at an almost constant rate, so that about 2% of the body's creatine and phosphocreatine pool, which is mostly in muscle, is converted to creatinine each day. Once creatinine reaches the bloodstream, it is filtered freely by the glomeruli and is neither reabsorbed nor secreted to any significant degree by the renal tubules.

Why Is Blood Creatinine Measured?

The main reasons are to detect and monitor acute kidney injury (AKI) and chronic kidney disease (CKD).

What Does an Increase in Blood Creatinine Indicate?

Blood creatinine concentration, measured in either plasma or serum, is interpreted mainly in relation to how well the kidneys eliminate it. When kidney function falls below a certain point, blood creatinine increases (hypercreatininemia), usually together with an increase in urea. "Azotemia" refers to an increase in either or both of these substances, but the focus here is on creatinine because of its central role in the IRIS systems for staging CKD and grading AKI.

Although an increased creatinine concentration occurs with substantial kidney dysfunction, other possibilities must also be considered, because a moderate increase can also be caused by:

  • High muscle production of creatinine, especially in breeds with large muscle mass, such as boxers, greyhounds, and sled dogs
  • A reduction in extracellular fluid volume: dehydration of more than 5% can increase blood creatinine
  • Intestinal absorption of creatinine from food, because some of the creatine in meat is converted to creatinine during cooking

What Are the Best Conditions for Measuring It?

  • Serum or plasma: creatinine concentrations are similar in serum and plasma.
  • Storage: creatinine is stable at 20°C for up to 24 hours in blood without anticoagulant, and for up to three days in plasma or serum. Frozen at −20°C, it remains stable for at least eight months.
  • Interference: hemolysis has no effect on blood creatinine. With assays based on the Jaffé reaction, which are still widely used in human laboratories but not in veterinary practice, high concentrations of bilirubin, lipids, and glucose can lead to overestimation. Cephalosporin antibiotics can increase creatinine values measured by the Jaffé method by up to 50%.

What Physiological Factors Affect Blood Creatinine?

  • Age: blood creatinine increases during growth, up to about one year of age. In healthy older dogs, blood creatinine is similar to that of young adults.
  • Body weight: blood creatinine increases with body weight. A large muscle mass can explain a moderately increased creatinine concentration, while muscle wasting, as in cachexia, can decrease it.
  • Breed: blood creatinine is generally higher in large breeds. However, concentrations vary widely between dogs of similar size, and there is considerable overlap between smaller and larger dogs. A recent study also found differences in creatinine between breeds (reference 1).
  • Time of sampling: there is no known variation in blood creatinine over the course of the day in dogs, but the possible effect of meals should be considered (see below).
  • Exercise: exercise may increase blood creatinine in greyhounds, by about 20% in the hour after exercise, but apparently not in sled dogs. In practice, an untrained dog can be sampled either immediately or some time after exercise, even strenuous exercise.
  • Feeding: eating can change blood creatinine. Increases of up to 50% may be seen one to four hours after a meal, especially when cooked meat is fed, because of absorption of creatinine formed from muscle creatine during cooking. It is therefore preferable to sample dogs after a fast of at least eight hours.

Is Blood Creatinine Sensitive for Detecting Kidney Dysfunction?

Blood creatinine is very useful, but it has limitations. In particular, the relationship between creatinine and glomerular filtration rate (GFR) is curvilinear: as GFR falls, creatinine rises slowly at first and then steeply. Therefore:

  • In the early stages of progressive kidney disease, GFR may decrease considerably without any obvious increase in blood creatinine, or with an increase so small that it stays within the reference range and may be dismissed as unimportant.
  • In the later stages of progressive kidney disease, even a modest further decrease in GFR causes a marked, rapid increase in blood creatinine.

The use of serum creatinine as a GFR marker has been questioned because of the physiological factors described above. Alternative markers of GFR that are not influenced by muscle mass include cystatin C and symmetric dimethylarginine (SDMA), and these have been suggested to perform better than creatinine in people and animals. However, data in dogs and cats are limited, and a 2019 study found that creatinine was not inferior to either cystatin C or SDMA when compared with measured GFR in 97 dogs (reference 2).

Two Approaches to Interpreting Blood Creatinine

A creatinine result can be interpreted in two ways.

Comparing a Single Value With a Reference Interval

A single value from a dog can be compared with the laboratory's reference interval. This is the usual approach when no earlier results are available, but it has limitations. Reference intervals differ between laboratories and methods, and they are wide, because they must cover dogs of every size, breed, and muscle mass. Because of the curvilinear relationship with GFR, a dog can lose a substantial part of its kidney function while its creatinine stays within the reference interval, especially a small or thin dog whose normal value is low. Conversely, a muscular dog or a greyhound may have a value slightly above the interval with normal kidneys.

For this reason, IRIS uses fixed creatinine cut-offs rather than laboratory reference intervals to stage CKD in dogs, and it interprets them alongside urine concentrating ability, proteinuria, SDMA, and the dog's hydration status. A dog is not staged on a single result: IRIS staging requires fasting creatinine values measured on at least two occasions in a stable, well-hydrated patient.

Comparing a Value With the Same Dog's Previous Results

A value can also be compared with earlier results from the same dog. Because the variation of creatinine within an individual dog is much smaller than the variation between dogs, a rise over time is a more sensitive sign of declining kidney function than a single value against a reference interval. A progressive increase, even within the reference interval, can indicate a falling GFR.

This approach works best when results are comparable. Ideally, samples should be taken after a fast of at least eight hours, with the dog well hydrated, and measured by the same laboratory using the same method. For suspected AKI, IRIS considers an increase of 0.3 mg/dL (26.4 µmol/L) or more within 48 hours to be significant, even if the values remain within the reference interval. Recording a baseline creatinine value while a dog is healthy, for example at an annual wellness visit, makes future results far more useful.

References

  1. Coyne M, Szlosek D, Clements C, McCrann D 3rd, Olavessen L. Association between breed and renal biomarkers of glomerular filtration rate in dogs. Veterinary Record 2020;187.
  2. Pelander L, Häggström J, Larsson A, et al. Comparison of the diagnostic value of symmetric dimethylarginine, cystatin C, and creatinine for detection of decreased glomerular filtration rate in dogs. Journal of Veterinary Internal Medicine 2019;33:630–639.

Further Reading

  • Braun JP, Lefebvre HP. Kidney function and damage. In: Kaneko JJ, Harvey JW, Bruss ML, eds. Clinical Biochemistry of Domestic Animals, 6th edition. Academic Press, Burlington, MA, 2008, pp. 485–528.
  • Pressler BM. Clinical approach to advanced renal function testing in dogs and cats. Veterinary Clinics of North America: Small Animal Practice 2013;43:1193–1208.