High creatinine in dogs. How should it be approached?

Introduction

In clinical practice, a high creatinine level is a common finding in dogs brought for consultation. A study in a referral hospital showed that 11.5% of all dogs whose creatinine level was measured for whatever reason had elevated concentrations.¹ 

Elevated creatinine levels are usually associated with kidney disease; however, not all dogs with kidney disease have high creatinine, nor does high creatinine necessarily imply the presence of intrinsic nephropathy.^2,3 Certain factors that can influence the result must be borne in mind in order to interpret the patient’s creatinine level correctly.

How to interpret high creatinine levels in dogs

Creatinine is a small molecule that comes from the cyclisation of creatine phosphate and creatine in skeletal muscle. It is eliminated through glomerular filtration and does not generally undergo tubular reabsorption or secretion (except for insignificant amounts in male dogs).These characteristics mean that creatinine can be used as an indirect marker of glomerular filtration rate (GFR), which is the best way of assessing overall kidney function, but unfortunately it cannot be measured in routine clinical practice.^2,3.  

At a functional level, creatinine and GFR have an inverse curvilinear relationship. This means that in the early stages of kidney disease, a significant decrease in GFR is not accompanied by a significant increase in creatinine concentration, whereas in advanced stages, small changes in GFR are associated with large increases in creatinine.^2-4 In fact, a high creatinine level in dogs was traditionally thought to indicate that 75% of renal function had already been lost, which would mean creatinine has a very low sensitivity as an indicator of kidney disease.^2,5 However, it is now known that this is not exactly the case because the compensatory phenomena that develop during kidney disease mean that even 13 months after a sudden loss of 75% of functional nephrons the decline in GFR is around 35–60%.³ A recent study in nonazotaemic dogs showed that if a cut-off of 1.36 mg/dL is applied, creatinine has a sensitivity/specificity of 80%/89% to a 40% reduction in GFR.⁶

Along with other criteria, creatinine levels can be used to establish the presence and classify the severity of acute kidney injury (AKI) and chronic kidney disease (CKD):

• The cut-off value for AKI is 1.6 mg/dL when other findings support the diagnosis, but an increase in creatinine of ≥0.3 mg/dL (which is still within the reference range) within 48 hours is diagnostic evidence of AKI stage 1.
• The cut-off for CKD is 1.4 mg/dL, again the diagnosis must be supported by other evidence of CKD.⁷  

Points to consider when assessing high creatinine levels in dogs:

1. Note that creatinine levels tend to be higher in large-breed dogs and very muscular patients (e.g., greyhounds). Some healthy animals in these groups can have creatinine concentrations of up to 2 mg/dL.⁸.
2. Furthermore, it is important to note that marked variations in creatinine levels have been reported depending on the analytical method and laboratory conducting the test. For the same sample, this variation can be up to 0.57 mg/dL in healthy or mildly azotaemic animals, and up to 1.32 mg/dL in patients with severe azotaemia. These differences may be even greater when comparing results obtained with biochemistry analysers used in veterinary clinics.³ 
3. It should also be noted that creatinine is usually slightly higher (0.05–0.1 mg/dL) in serum than in plasma. It is important to inspect the serum/plasma visually before testing the sample, as haemolysis may increase creatinine concentration depending on the analytical method used, while lipaemia and jaundice can reduce it.^4,5
4. Creatinine levels are also known to increase after ingesting certain foods.
5. Furthermore, like any other indicator of GFR, creatinine increases with dehydration or in patients with a urinary obstruction, even in the absence of intrinsic kidney disease.³

Taking all these factors into account, creatinine should be measured in a fasting patient (where possible), in either serum or plasma, but always in the same type of sample, and ideally on the same analyser and applying the same technique.

Conclusions

A high creatinine level is a common finding in dogs brought for consultation. As vets we instinctively suspect kidney disease, but before making a diagnosis, we must consider whether the patient has any extrarenal factors known to influence creatinine concentrations.

Next, it is important to assess the values of other parameters that may be elevated in patients with kidney disease: SDMA, urine specific gravity, proteinuria, phosphataemia.

If the results are incompatible, the blood test should be repeated once the patient is stable. Creatinine levels in patients with AKI may normalise within a few hours or days, depending on the severity of the AKI, or, on the other hand, the azotaemia may be significantly worse.

In contrast to cases of AKI, in dogs with suspected azotaemic CKD, unless the condition is mild enough to be corrected through rehydration, the elevated creatinine level will persist once the patient is hydrated.

References

1. Babyak JM, Weiner DE , Noubary F, et al. (2017). Prevalence of elevated serum creatinine concentration in dogs presenting to a Veterinary Academic Medical Center (2010-2014). J Vet Intern Med; 31: 1757-1764. 

2. Heine R, Lefebvre H. Assessment of renal function. In: Elliot J, Grauer F (Eds). BSVA Manual of Canine and Feline Nephrology and Urology. British Small Animal Association. Gloucester, 2007:117-125.

3. Hokamp JA, Nabity MB. (2016). Renal biomarkers in domestic species. Vet Clin Pathol; 45: 28-56.

4. Yerramilli M, Farace G, Quinn J, et al. (2016). Kidney disease and the nexus of chronic kidney disease and acute kidney injury: the role of novel biomarkers as early and accurate diagnostics. Vet Clin North Am Small Anim Pract; 46: 961-993.

5.  Relford R, Robertson J, Clements C. (2016). Symmetric dimethylarginine: improving the diagnosis and staging of chronic kidney disease in small animals. Vet Clin North Am Small Anim Pract; 46: 941-960.

6. McKenna M, Pelligand L, Elliott J, et al. (2020). Relationship between serum iohexol clearance, serum SDMA concentration, and serum creatinine concentration in non-azotemic dogs. J Vet Intern Med; 34:186-194

7.  http://iris-kidney.com/guidelines/index.html. Last accessed on 12/07/2021.

8. A. Craig, J. Seguela, Y. Queau, et al. Redefining the reference interval for plasma creatinine in dogs: effect of age, gender, body weight, and breed. J Vet Intern Med, 2006; 20: 740.