What is a urine protein:creatinine ratio?
The urine protein:creatinine (UPC) ratio is a simple test that measures how much protein is being lost through the kidneys. It is used to determine whether a pet may have serious kidney disease (see handout "Urine Protein"). The test involves measuring the amount of protein and creatinine in the same urine sample, and expressing the difference between the two values as a ratio.
What is creatinine and why is it used in this test?
Creatinine is a substance that appears in the blood as the result of muscle activity. Creatinine is excreted by the kidney at a constant rate, which means it can be used as a gauge to assess the rate of excretion of other substances. For example, the urine protein:creatinine ratio measures whether the excretion of protein is greater than expected when compared to the excretion of creatinine.
Is protein loss through the kidney always significant?
Most of the time, but not always. Losing trace amounts of protein through the kidneys may not be significant if the kidneys are working well otherwise, and the urine is well concentrated (see handout "Urinalysis"). If kidney function is abnormal or the urine is consistently dilute, then even a tiny amount of protein in the urine could be an indicator of true kidney disease and even kidney failure.
Does all urinary protein come from the kidneys?
No. Protein can be found in urine for many reasons other than kidney disease. Bleeding and inflammation in the urinary system are common causes, and are associated with disorders such as bladder infection, bladder stones, prostate disease (in males), vaginitis (in females), cancer, and others. If substantial protein is detected in the urine, and there is no inflammation or bleeding, then true kidney disease is likely present.
Can any urine sample be used to measure protein:creatinine ratio?
No. The protein:creatinine ratio should be performed only on urine that is free of blood and inflammatory cells. A complete urinalysis and sediment evaluation should be completed first to determine if the sample is suitable for the protein:creatinine test. This is because the presence of blood and inflammation may give a falsely high ratio, suggesting kidney disease is present when there is some other cause.
Are any other tests needed to interpret the protein:creatinine ratio?
Yes. Before the protein:creatinine ratio can be interpreted, two other measures of kidney function should be taken. These are blood urea nitrogen (BUN) and serum creatinine. These blood tests indicate how well the kidneys are working.
"Before the protein:creatinine ratio can be interpreted, two other measures of kidney function should be taken."
An additional blood test for kidney function called symmetrical dimethylarginine (SDMA) is also available from some laboratories. This particular parameter becomes elevated in kidney disease before BUN and creatinine, and so is better able to detect kidney disease sooner.
How is the protein:creatinine ratio interpreted?
- High values for both BUN and creatinine indicate that the kidneys are not working well and may be in failure. In this situation a urine protein:creatinine (UPC) ratio greater than 0.4 in a cat and 0.5 in a dog indicates there is significant protein loss through the kidneys, and a diagnosis of primary kidney disease can be made. Further investigation and treatment are recommended.
- Normal BUN and creatinine values suggest the kidneys are likely healthy and working well. In this situation a protein:creatinine (UPC) ratio up to 2.0 in both cats and dogs is acceptable.
- If the ratio is greater than 2.0, then significant protein loss through the kidneys exists, even if BUN and creatinine are within normal limits. Primary kidney disease is likely present and further investigation and treatment are recommended.
Is one protein:creatinine ratio enough?
No. Before a diagnosis of primary kidney disease can be made, it is necessary to prove that the protein loss through the kidney is an ongoing problem. The recommendation is to repeat the protein:creatinine ratio (with complete urinalysis) on at least three consecutive urine samples taken at 2-week intervals. The longer the protein loss goes on, the more likely it is that serious kidney disease is present.
In a pet with confirmed primary kidney disease, the urine protein:creatinine ratio can be used to monitor kidney function to see if there is improvement in response to treatment.
In a pet with borderline disease, repeat urine protein:creatinine ratios are recommended every 3-6 months to monitor kidney function in order to detect any deterioration in the pet’s condition.
Does an elevated protein:creatinine ratio explain the underlying problem?
No. The protein:creatinine ratio only helps to establish that a problem exists. Further investigation is required to determine the cause and may include testing for bacterial infection or infectious disease, performing an ultrasound of the kidneys and possibly doing a kidney biopsy to look at the kidney tissue directly. Once a complete diagnosis is made, plans can be made to manage the disease as effectively as possible.