Hervé Lefebvre, Department of Physiology and Pharmacology,National Veterinary School, Toulouse, France, and  David Watson, Department of Veterinary Clinical Sciences, The University of Sydney, Australia. 2001
 

Why is plasma creatinine measured?
 

Mainly to detect or monitor acute or chronic renal insufficiency.
 

What is the meaning of an increase in plasma creatinine?
 

Plasma or serum creatinine concentration is generally interpreted only from the point of view of renal  elimination, i.e., plasma creatinine increases when renal function decreases, but (even if less frequently) moderate hypercreatininemia may also be explained by:
 

• High muscle production of creatinine, especially in dog breeds with large muscle mass (such as boxers, greyhounds, sled dogs, etc.).
• Reduction in extracellular fluid volume, e.g., dehydration, may increase plasma creatinine concentration considerably.
• Intestinal absorption of exogenous creatinine. (continued from preceding page)

What are the optimal analytical conditions?
 

• Serum vs. plasma: creatinine concentrations are similar in serum and plasma.
• Storage: Creatinine is stable at 20°C up to 24 hours in blood without anticoagulant and up to three days in plasma or serum. At –20°C, stability is excellent (at least eight months).
• Analytical interferences: Haemolysis has no effect on creatininemia. If the assay is based on Jaffé’s reaction (still largely used in human laboratories, but not in veterinary practice), high concentrations of bilirubin, lipids, and glucose may interfere with creatininemia and lead generally to overestimation of plasma creatinine values. Cephalosporins may increase plasma creatinine values determined by Jaffé’s method by up to 50%.

What physiological factors affect creatinine concentration?
 

• Age: Creatininemia increases during growth in the puppy. In the healthy geriatric dog, plasma creatinine is similar to that observed in young adults.
• Body weight: No clear relationship is apparent, but large muscle mass may explain moderately elevated plasma creatinine concentration. In contrast, muscle atrophy in cachexia may decrease plasma creatinine values.
• Time of sampling: No variation in creatininemia throughout the day in dogs is known (but consider possible effects of meals).
• Exercise: Exercise may increase plasma creatinine concentration in greyhounds (by about 20% in the 60 minutes following exercise), but apparently not in sled dogs. Practically speaking though, an untrained dog can be sampled either immediately, or later, after exercise (even if strenuous).
• Feeding: Food intake is a potential cause of variation of creatinine concentrations. Increased plasma creatinine (up to 50%) may be observed one to four hours after a meal, especially when cooked meat is given. This increase is explained by intestinal absorption of exogenous creatinine generated from muscle creatine during cooking. It is probably preferable, therefore, to sample the dog in the fasted state (at least eight to ten hours).

Is creatinine sensitive enough to detect renal dysfunction?
 

While creatinine assay is useful, some limitations have to be kept in mind:

• The relationship between creatinine and GFR is curvilinear, which means that GFR may decrease rapidly in the early stages of renal insufficiency without major increases in plasma creatinine (or variations only within the reference range, and thus potentially considered as clinically irrelevant) and, on the contrary, plasma creatinine may increase dramatically in the latter stages with even modest decreases in GFR.
• Plasma creatinine concentration may be interpreted by two different approaches:
  
  1. Comparison of a single isolated value from a given dog to the reference interval. This approach is often the only one available, but is not ideal. Reference intervals have generally been poorly defined on limited numbers of animals and can differ greatly between countries and assays. No decision threshold can thus be transferred from one lab to another, or from published values to your own practice, unless the conditions are strictly the same. Hypercreatininemia identified from a single sample does not necessarily mean renal dysfunction is present, but certainly indicates a need for other tests (urine-specific gravity, proteinuria, etc.) to further assess renal function and disease.
  
  2. Comparison of a value obtained at a particular time in a given dog to another value obtained in the same dog at a previous time. If conditions are standardized (same technique, fasted dog, etc.), this is probably a better way to monitor renal function over time. An increase or a decrease in creatinine generally indicates a decrease or an increase in renal function, respectively (but consider possible effects of reduced muscle mass in cachexia – see previously). This approach is particularly recommended in animals with identified renal insufficiency or to detect early nephrotoxic effects of drugs (even if other markers such as enzymuria may be considered more sensitive). Determination of fasting plasma creatinine concentration should probably be undertaken as part of any routine health-monitoring program in the older dog.