Urine Protein and Urine Protein to Creatinine Ratio
As part of a routine physical, often as part of a urinalysis; urine total protein and urine protein to creatinine ratio (UPCR) have traditionally been used as important indicators of kidney disease and as a follow-up testing for monitoring the disease. However, albumin to creatinine ratio (ACR) is now the preferred testing for these purposes.
A single urine sample is collected in a clean container at any time (random/spot). For a 24-hour urine collection, the collection process generally begins first thing in the morning by discarding the first morning void and then collecting all of the urine for the remaining 24-hour period. The sample must be refrigerated during this period. There should be no preservatives in the container. Occasionally, a split 24-hour sample, with the night collection (11 pm to 7 am) separated from the day collection (7 am to 11 pm), may be used. Often, a blood sample may also be taken to measure your creatinine and serum protein levels, especially when 24-hour urine has been ordered.
Since the results from both types of sample collection methods are highly correlated, the spot urine collection may be used as a rapid and reliable alternative for UPCR measurement.
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Urine protein tests detect and/or measure protein being released into the urine. Normal urine protein elimination is less than 150 mg/day and less than 30 mg of albumin/day. Elevated levels may be seen temporarily with conditions such as infections, stress, pregnancy, diet, cold exposure, or heavy exercise. Persistent protein in the urine suggests possible kidney damage or some other condition that requires additional testing to determine the cause.
There are several different kinds of urine protein tests, including:
- A semi-quantitative protein "dipstick" may be performed as part of a urinalysis, generally on a random urine sample.
- The quantity of protein in a 24-hour urine sample may be measured and reported as the amount of protein released per 24 hours.
- The amount of protein in a random urine sample may be measured along with urine creatinine and reported as the ratio of urine protein to creatinine (UPCR).
Creatinine, a byproduct of muscle metabolism, is normally released into the urine at a constant rate. When both a urine creatinine and a random urine protein test are performed, the resulting protein/creatinine ratio approaches the accuracy of the 24-hour urine protein test. Since saving all of the urine for 24 hours can be cumbersome for adults and difficult for infants and children, a random urine protein to creatinine ratio is sometimes substituted for a 24-hour urine protein sample.
Plasma proteins are essential for all living beings. The kidneys, two organs found in the back at the bottom of the rib cage, recapture these proteins by filtering the blood by removing wastes and eliminating them from the body in the urine. When the kidneys are functioning normally, they retain or reabsorb the filtered proteins and return them to the blood.
However, if the kidneys are damaged or compromised due to other conditions, they become less effective at filtering, causing detectible amounts of protein to spill over into the urine. Routine dipstick testing of urine measures the presence of albumin. Albumin, a protein produced by the liver, makes up about 50%-60% of the protein in the blood. The rest is a mixture of globulins, including immunoglobulins. As kidney damage progresses, the amount of albumin in the urine increases, a key factor in the early detection of a potential kidney disorder.
Protein in the urine, also called proteinuria, is frequently seen in chronic diseases, such as diabetes and/or hypertension, with increasing amounts of protein in the urine reflecting increasing kidney damage. There are often no signs and symptoms with early kidney damage. As kidney damage progresses, or if protein loss is severe, you may develop symptoms such as fluid build-up (edema), shortness of breath, nausea, and fatigue. The production of too much protein, as seen with multiple myeloma, lymphoma, and amyloidosis, can also lead to proteinuria.
The presence of albumin in the urine (albuminuria) is a sensitive indicator of kidney disease in people with diabetes and/or hypertension. Therefore, it is recommended that people with these conditions be regularly screened for albumin in the urine, as opposed to total urine protein (see Urine Albumin).
How is the test used?
Urine protein testing is used to detect excess protein in the urine (proteinuria). A semi-quantitative test such as a dipstick urine protein may be used to screen for the presence of protein in the urine as part of a routine urinalysis.
A urine protein test may be used to screen for, help evaluate, and monitor kidney function and to help detect and diagnose early kidney damage and/or disease. However, the test can also help screen for several other conditions that can cause proteinuria.
If slight to moderate amounts of protein are detected, then a repeat urinalysis and dipstick protein may be performed at a later time to see if there is still protein in the urine or if it has become undetectable.
If there is a large amount of protein in the first sample, repeat testing will be ordered. If increased levels of urine protein are observed in follow-up specimens, then a 24-hour urine protein may be ordered along with certain blood tests. Since the dipstick method primarily measures the protein albumin, and if follow-up, repeat urine samples are positive, a 24-hour urine test also may be ordered to obtain more detailed information.
A urine protein to creatinine ratio (UP/CR) may be ordered on a random urine sample if there is evidence of significant and persistent protein in the urine. Children and sometimes adults occasionally have some degree of transient proteinuria without apparent kidney dysfunction and may release more protein into their urine during the day than at night. The healthcare practitioner may monitor their urine at intervals to see if the amount of proteinuria changes over time.
Either a 24-hour urine protein or a random protein to creatinine ratio may be used to monitor a person with known kidney disease or damage. A dipstick urine protein and/or a protein to creatinine ratio may be used to screen people on a regular basis when they are taking a medication that may affect their kidney function.
When is it ordered?
A dipstick urine protein is measured (primarily albumin) frequently as a screening test whenever a urinalysis is performed. This may be done as part of a routine physical, a pregnancy workup, when a urinary tract infection is suspected, as part of a hospital admission, or whenever a healthcare practitioner wants to evaluate kidney function. Repeat testing may also be done when a previous dipstick has been positive for protein to see if the protein persists.
Specifically for monitoring people with possible kidney dysfunction, the National Kidney Foundation has established a 5-step plan for chronic kidney disease (CKD) evaluation and referral using random (spot) urine albumin-to-creatinine ratio (ACR), rather than random UPCR, to screen for and determine the prognosis of CKD, for urine protein is more difficult to standardize. (For more details, see the article on Urine Albumin.)
A 24-hour urine protein may be ordered as a follow-up test, especially in pregnant women with a high pre-screen risk of preeclampsia, when the dipstick test shows that there is a large quantity of protein present in the urine or when protein is shown to be persistently present.
Since the dipstick primarily measures albumin, the healthcare practitioner may order a 24-hour urine protein test even when there is little protein detected on the dipstick if the practitioner suspects that there may be proteins other than albumin being released.
A protein to creatinine ratio may be ordered on a random urine sample when a child shows evidence of significant and persistent protein in their urine with the dipstick urine test.
Urine protein testing may be ordered on a regular basis when you are taking a medication that may potentially affect kidney function, including certain antibiotics, analgesics, COX-2 inhibitors (some non-steroidal anti-inflammatory drugs), and proton pump inhibitors (gastric reflux).
What does the test result mean?
A negative test result means that there is no detectable amount of protein in the urine at the time of testing.
Protein detected in a random urine sample may be temporary due to an infection, medication, vigorous exercise, pregnancy, diet, cold exposure, or emotional or physical stress. Testing should be repeated after these conditions have resolved.
Protein in the urine can also be a warning sign of a serious condition and usually warrants further investigation. Typically, three positive urine samples over a period of time without other significant symptoms will often be followed up with additional tests, including a 24-hour urine.
Persistent and/or an increased amount of protein in the urine may indicate kidney damage or disease. With kidney disease, the amount of protein present is generally associated with the severity of the damage. Increasing amounts of protein over time indicate increasing damage and decreasing kidney function. The most common cause of protein in the urine is kidney damage resulting from:
- Diabetes – proteinuria is one of the first signs of deteriorating kidney function in people with type 1 and 2 diabetes.
- High blood pressure (hypertension) – proteinuria in someone with high blood pressure is also a first sign of declining kidney function.
Proteinuria may also be seen with many other diseases and conditions. A healthcare practitioner may order other tests and take into account those results to help determine the cause. Some examples of these causes include:
- Urinary tract infection
- Multiple myeloma
- Bladder cancer
- Congestive heart failure
- Drug therapies that are potentially toxic to the kidneys
- Goodpasture syndrome
- Heavy metal poisoning
For more details, select the links from the list above, or read the article on Proteinuria.
If I have a positive urine protein test, what other tests might be done in follow up?
A positive urine protein test tells your healthcare practitioner that protein is present in your urine, but it does not indicate which types are present or the cause of the proteinuria. When investigating the reason, your healthcare practitioner may order additional laboratory tests, such as:
- Comprehensive metabolic panel (CMP)—includes tests such as BUN, creatinine, albumin and total protein, which help evaluate kidney and liver function
- A full urinalysis—if a condition such as urinary tract infection is also suspected
- Serum and urine protein electrophoresis test—to determine which proteins are being released into the urine and in what quantities; this is especially true if your healthcare practitioner suspects abnormal monoclonal protein production, such as with multiple myeloma or lymphoma.
See the article on Proteinuria for more on follow-up tests.
If kidney disease or damage is suspected, your healthcare practitioner may also order imaging scans (ultrasonography or CT scan) to evaluate the appearance of your kidneys.
Is there anything else I should know?
The different methods of detecting protein in the urine vary in performance. For example, a positive dipstick protein may be elevated due to other sources of protein, such as blood, semen, or vaginal secretions in the urine. Since it measures primarily albumin, the dipstick may occasionally be normal when significant quantities of other proteins are present in the urine.
A 24-hour urine sample gives the protein elimination rate over 24 hours. It will be accurate only if all of the urine is collected. The protein to creatinine ratio is more of a snapshot of how much protein is in the urine at the time the sample is collected. If it is elevated, then protein is present; if it is negative, the amounts or the type of protein released in urine may not be detectable at that time.
Can I test for protein in my urine at home?
Does kidney damage go away?
In general, it does not. The goal is to detect kidney disease and damage early to minimize the damage and prolong kidney function. If the proteinuria detected is due to a kidney infection or urinary tract infection, the kidneys frequently will return to normal function as the infection resolves. If it is due to a medication, then in most cases the kidneys are likely to return to normal or near-normal function when the medication is stopped.
Should I eat more protein to make up for lost protein?