Proteinuria is the excretion of protein in the urine. This condition is often an early warning sign of progressive kidney disease such as diabetic nephropathy. The loss of kidney function is one of several serious complications that can result from diabetes, particularly among those who have difficulty controlling their glucose (blood sugar) or blood pressure.
Proteinuria can also indicate high blood pressure and cardiovascular damage, which are also common complications of diabetes.
The kidneys are made up of millions of nephrons, which contain tiny clusters of blood vessels. These clusters, known as glomeruli, filter the blood and produce urine. Then the urine moves down into the collection ducts, through the ureters to the urinary bladder and through the urethra for expulsion from the body.
Although undetectable in normal urine tests, the beginning stages of proteinuria appear with the thickening of the glomeruli. In this early stage, the kidneys begin to let small amounts of albumin (the most common protein found in urine) pass through to the urine. Only highly sensitive tests can detect the presence of albumin at this stage, which is referred to as microalbuminuria.
Kidney disease normally progresses in three stages from microalbuminuria to proteinuria (larger quantities of protein in the urine) to end-stage renal disease (ESRD), in which the kidneys fail and dialysis or a kidney transplant is needed. Over the course of several years, diabetic nephropathy causes hyperfiltration, whereby increasingly large amounts of blood pass through the filters of the kidneys. Over time, the kidneys become worn down by this process. More and more protein begins to leak from the bloodstream into the urine, starting with microalbuminuria. If microalbuminuria goes undetected or untreated, proteinuria will result.
With the progression of microalbuminuria to proteinuria, which can take as many as five to 10 years, more and more glomeruli become damaged. This, in turn, causes more essential protein to leave the body through the urine.
Once proteinuria has developed, enough protein is present in the urine to be detected through a normal urine test. If left untreated, proteinuria can lead to ESRD within two to six years.
The two biggest risk factors for developing protein in the urine (proteinuria) are diabetes and high blood pressure. African Americans, American Indians, Hispanic Americans, Pacific Islander Americans, the elderly and overweight people are at a higher risk of developing proteinuria.
Although diabetes and high blood pressure (hypertension) are most commonly associated with proteinuria, other factors can result in temporary proteinuria.
- Dehydration or heat-related injury
- Fever, infection or acute illness
- Emotional stress
- Intense physical activity
- Extreme cold
- Abdominal surgery
- Administration of epinephrine
Another form of this condition, which is considered fairly common in adolescents, is postural or orthostatic proteinuria. In most cases, protein in the urine is detected in a routine screening of the child and normally appears without the presence of other symptoms. In these patients, a significant amount of protein leaks into the urine when they are upright (orthostatic). The level of protein in the morning may be normal.
It is believed that standing adds to the pressure on the kidneys’ filtering agents, which in turn causes more protein to leak into the urine. Conversely, when lying down, the pressure is relieved and little or no protein gets through. The concentration of protein in orthostatic proteinuria is often greater in the afternoon than in the morning. Most adolescents who have this condition outgrow it.
In addition to the temporary causes of proteinuria, and the benign forms of the condition, the filtering units of the kidneys can become damaged from other diseases and conditions that are more serious. Though these diseases have many causes, each has been known to lead to damage of the kidneys’ glomeruli and to proteinuria:
- Many kidney conditions, including glomerular disorders, polycystic kidney disease (PKD) and hereditary nephritis (Alport syndrome).
- Amyloidosis. A disorder in which amyloid, a starchy protein, accumulates in tissues and organs. Conditions associated with amyloidosis include osteomyelitis, cancer, tuberculosis, leprosy and dialysis.
- Certain autoimmune diseases, including lupus and rheumatoid arthritis.
- Cardiovascular conditions including heart failure, atherosclerosis, infection (endocarditis) and some cases of a pediatric heart disorder called Kawasaki disease.
- Other infections. These include hepatitis, HIV (human immunodeficiency virus) streptococcus infection (strep throat), typhoid fever and impetigo, an inflammatory skin disorder.
- Preeclampsia. A condition that can develop during pregnancy. It includes proteinuria and high blood pressure and can lead to eclampsia.
- Heavy-metal poisoning.
- Other conditions that can damage the kidneys. These include hyperuricemia (excess uric acid in the blood) and gout, sickle cell anemia, sarcoidosis, malaria, some cancers, and certain metabolic disorders such as glycogen storage disease.
- Certain drugs. These include aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), penicillamine, lithium, heroin, gold salts and possibly some statin cholesterol drugs.
Protein in the urine can be present for as many as five to 10 years before any symptoms appear. However, foamy urine, fluid retention and swelling (edema) are sometimes seen in patients with proteinuria. However, edema often occurs only in the latter stages of proteinuria.
As more and more protein is leaked into the urine, the amount of protein in the blood drops below the level needed for good health. Albumin (the most common protein found in urine) is necessary for blood to retain water within the arteries and capillaries. As the albumin level drops in the blood – because it is being leaked out through urine – water can accumulate in the tissues and cause swelling in the chest, legs or abdomen.
Although undetectable in normal urine tests, the beginning stage of proteinuria (microalbuminuria) frequently appears without any outward signs or symptoms. Protein in the urine may be present for several years before other, concurrent indicators of diabetic nephropathy begin to appear, such as high blood pressure, diabetic retinopathy or vascular (blood vessel) changes.
Proteinuria, the presence of large amounts of protein in the urine, is a common sign of diabetic nephropathy. Several types of urine tests can indicate proteinuria. Although there are benign or less serious causes, such as heavy exercise or urinary tract infection (UTI), proteinuria more often signals the development of kidney disease. It can also be a sign of high blood pressure and an indication of cardiovascular disease.
When only small amounts of protein are present in the urine, a condition known as microalbuminuria, a routine urine test is not sensitive enough for diagnosis. Specialized urinalysis called a microalbuminuria test is used.
- Personal and family medical history
- The presence of UTI symptoms
- Drug exposure
- Growth history
- Recent infections
- Hepatitis B status and human immunodeficiency virus (HIV) risk factors
- Joint symptoms
- Blood pressure
- Protein electrophoresis. Because proteins are electrically charged they can be separated by their individual charges through electrophoresis, the use of an electrical field to separate charged particles.
- Proteinuria test or “dipstick” urine test. Depends on a reaction of protein to cause a color change of the indicator dye.
- Creatinine. The protein-to-creatinine or albumin-to-creatinine ratio can be measured in a sample of urine to detect smaller amounts of protein. If the laboratory tests show high levels of protein, another test should be conducted one to two weeks later. On a related note, it is sometimes recommended that a blood sample be taken to check for creatinine and urea nitrogen as these are waste products that healthy kidneys would normally remove from blood. Thus, the presence of high levels of creatinine and urea nitrogen in the blood may show that the kidneys are not functioning properly.
- 24-hour urine protein. A collection of all urine excreted in a 24-hour period is sometimes used to evaluate the presence of protein in the urine and is considered the gold standard, according to the National Kidney Foundation.
- Microalbuminuria dipstick test. Chemically treated paper is dipped in a urine sample. It will change color if protein, specifically albumin, is present in the urine.
The physician may also choose to conduct other assessments of kidney function, including waste product tests, glomerular filtration rate testing, blood tests such as total serum protein or an electrolyte panel, or imaging tests such as ultrasound to detect possible scarring.
When protein is detected in the patient’s urine and diabetic nephropathy is diagnosed, the goal of treatment is to slow the progression of kidney damage, as well as any related complications.
A common treatment is ACE inhibitors
. These drugs are used to reduce the levels of protein in the urine and slow the onset of the nephropathy. Some physicians use angiotensin-II receptor blockers (ARBs) instead of or in combination with ACE inhibitors.
- Controlling glucose (blood sugar). The Diabetes Control and Complication Trial and other research projects have shown that better glycemic control can prevent or slow the progression of diabetic kidney disease.
- Controlling high blood pressure (hypertension). Kidney scarring raises blood pressure, and high blood pressure in turn speeds the rate of kidney damage by weakening the capillaries of the glomeruli. Either a family history of hypertension or the presence of high blood pressure increases the risk for developing kidney disease.
- Treating urinary tract infections (UTI) quickly. With a direct connection between the urinary tract and the kidneys, bacteria have an easy pathway to spread. For this reason, and others, any UTI requires immediate treatment. Symptoms of a UTI include pain or burning during urination, frequently feeling the need to urinate, cloudy urine, blood in urine, fever and lower back pain.
- Controlling diet. A low-protein diet may reduce or even prevent damage to glomeruli and slow the progression of kidney disease. In addition, the National Kidney Foundation recommends limiting the amount of dietary salt and protein for those with kidney disease.
- Beta blockers. With a similar action to ACE inhibitors, some research suggests that beta blockers, another class of antihypertensive drugs, can reduce the levels of protein in the urine, as well as improve glomerular filtration rate.
In addition, scientists are studying potential drug treatments for diabetic nephropathy, including medications that address proteinuria.
About 10 to 20 percent of people with diabetes have diabetic nephropathy, the leading cause of end-stage renal disease (ESRD), according to the American Diabetes Association (ADA). This is a serious complication as those who develop ESRD must undergo dialysis or receive a kidney transplant to live. In fact, for people with type 1 diabetes, ESRD or death often occurs within five to 10 years of developing persistent proteinuria, according to the ADA.
The earlier protein is detected in the urine and the smaller the quantity of protein in the urine, the better a patient’s chances for preventing long-term damage to the kidneys. It is highly recommended that testing for microalbuminuria (a condition in which small amounts of protein are present in the urine) and proteinuria be performed each year, starting upon diagnosis of type 2 diabetes and five years after a diagnosis of type 1. For children with diabetes, testing should start at puberty and then occur yearly throughout life.
In addition, people with diabetes should consult their physician before receiving certain contrast dyes used in some x-ray and other imaging tests, including barium, iodine and gadolinium. In cases where the dyes cannot be avoided, additional fluid intake to ease excretion of the dyes is recommended.
People with diabetes are advised to ask their physician about whether they need to limit or avoid medications that can damage the kidneys, including nonsteroidal anti-inflammatory drugs (NSAIDs)
such as aspirin, ibuprofen, naproxen and COX-2 inhibitors.
Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about proteinuria:
- Do I have, or am I at risk of developing, proteinuria or microalbuminuria?
- How do my diabetes and blood pressure affect my risk of proteinuria?
- What should I know about the difference between proteinuria and microalbuminuria?
- What tests should I have to detect or monitor these conditions?
- How often should I have these tests?
- Do I need to do anything to prepare for the testing?
- What do my test results show?
- Does having proteinuria mean I have diabetic nephropathy or another type of kidney disease?
- Could proteinuria also mean I have heart problems, preeclampsia or some other condition?
- Do I need medication, dietary restrictions or other treatment?
- How can I control my risk of proteinuria and kidney damage?
- Can aspirin, ibuprofen or other medications I take contribute to proteinuria?
There are no complications of albuminuria. Any complications are due to the underlying disease.
There is an increased risk of developing diabetes in individuals with microalbuminuria.
Albuminuria is a laboratory finding. Any condition associated with albuminuria must be included in the differential diagnosis.
Internist and endocrinologist.