What is proteinuria

Proteinuria is also called albuminuria, is a condition characterized by the presence of greater than normal amounts of protein (albumin) in your urine. The job of your kidneys is to filter out waste, extra fluid, and salt. These wastes leave the body in urine and usually only a small amount of protein is found in urine because most proteins are too big to be filtered through the kidneys.Proteinuria is usually associated with some kind of disease or abnormality but may occasionally be seen in healthy individuals.

Plasma, the liquid portion of blood, contains many different proteins. One of the many functions of the kidneys is to conserve plasma protein so that it is not eliminated along with waste products when urine is produced. There are two mechanisms that normally prevent protein from passing into urine:

• The glomeruli provide a barrier that keeps most larger plasma proteins inside the blood vessels.
• The small proteins that do get through are almost entirely reabsorbed by the tubules.

Proteinuria most often occurs when either the glomeruli or tubules in the kidney are damaged. Inflammation and/or scarring of the glomeruli can allow increasing amounts of protein and sometimes red blood cells to leak into the urine. Damage to the tubules can prevent protein from being reabsorbed. Proteinuria may also develop when too much of a small protein is present in the blood and the tubules cannot reabsorb all of it.

Healthy people can have temporary or persistent proteinuria. It may be associated with stress, exercise, fever, aspirin therapy, and exposure to cold. Some people release more protein into the urine when they are standing up than when they are lying down (orthostatic proteinuria), though this condition is rare in individuals over age 30. However, a detectable level of protein in the urine usually indicates the presence of an underlying disease or condition and warrants further investigation to determine the cause.

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.
• Hypertension – proteinuria in someone with high blood pressure is also a first sign of declining kidney function.

Others causes of kidney damage resulting in proteinuria include:

• Immune disorders (e.g., lupus, IgA nephropathy, Goodpasture’s syndrome)
• Infections
• Exposure to toxins
• Trauma
• Kidney cancer
• Congestive heart failure

Some other conditions that can cause proteinuria include:

• Red blood cell destruction and release of hemoglobin that occurs in the bloodstream (intravascular hemolysis)
• Pre-eclampsia – pregnant women are routinely screened for proteinuria because its presence is associated with pre-eclampsia (also known as toxemia of pregnancy). Pre-eclampsia is a pregnancy-specific disorder where proteinuria and hypertension develop at the same time. Symptoms can include edema (swelling), nausea, and headaches during pregnancy. Rarely, it can cause severe symptoms such as seizures. Pre-eclampsia can be dangerous for both the mother and her baby.
• Multiple myeloma (cancer of the plasma cells) – proteinuria due to the presence of excess proteins in blood that overflow into the urine (Bence-Jones protein) may be seen in multiple myeloma. Bence-Jones protein consists of an abnormal immunoglobulin light chain (either kappa or lambda) that is produced by monoclonal plasma cells. All immunoglobulins are composed of four protein chains, two light chains and two heavy chains. Bence-Jones protein is made of two immunoglobulin light chains and its presence in urine is often diagnostic of multiple myeloma in the context of other symptoms.

People who are at increased risk for kidney disease should have proteinuria test as part of routine checkups by a healthcare provider. Those at increased risk include:

• People with diabetes
• People with high blood pressure
• People with a family history of kidney failure
• People who are 65 years or older
• Certain ethnic groups including African Americans, Hispanics, Asians, American Indians

Proteinuria levels

For a random urine sample, normal values are 0 to 20 mg/dL.

For a 24-hour urine collection, the normal value is less than 80 mg per 24 hours.

The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your provider about the meaning of your specific test results.

What is albuminuria?

Albuminuria is the presence of albumin in your urine. Albumin is a type of protein that is normally found in the blood. Your body needs protein. It is an important nutrient that helps build muscle, repair tissue, and fight infection. But protein should be in your blood, not your urine.

One of the main jobs of your kidneys is to filter your blood. When your kidneys are healthy, they keep important things your body needs inside your blood, like protein. They also remove things your body doesn’t need, like waste products and extra water.

If your kidneys are damaged, protein can “leak” out of the kidneys into your urine. Having protein in your urine is called “albuminuria” or “proteinuria.”

Albuminuria may be an early sign of kidney disease, but your doctor will check you again to make sure albuminuria is not caused by something else, like not drinking enough water. If your doctor suspects that you have kidney disease, the urine test for albumin will be repeated. Three positive results over three months or more is a sign of kidney disease.

You will also be given a simple blood test to estimate glomerular filtration rate (GFR). Your GFR number tells you how well your kidneys are working.

You may also be given:

• Imaging tests. (An ultrasound or CT scan). This produces a picture of your kidneys and urinary tract. It can show whether your kidneys have kidney stones or other problems.
• A kidney biopsy. This can help find out what caused your kidney disease and how much damage to the kidneys has happened.

If I have albuminuria, will I need treatment?

If kidney disease is confirmed, your healthcare provider will create a treatment plan for you. You may also be asked to see a special kidney doctor called a nephrologist. Your treatment may include:

• Medications
• Changes in your diet
• Lifestyle changes such as losing extra weight, exercising, and stopping smoking.

Proteinuria in pregnancy

Proteinuria in pregnancy is an important early sign for the diagnosis of pre-eclampsia. Pre-eclampsia is one of the most serious conditions affecting pregnant women. Pre-eclampsia is diagnosed when a woman develops high blood pressure (hypertension), protein in her urine (proteinuria), and/or swelling of the hands, feet and/or face during pregnancy. In severe cases, there may be evidence of damage to the kidneys or liver, accumulation of fluid in the lungs, or disturbances of the central nervous system. About 3 to 7 percent of pregnant women develop pre-eclampsia, which can occur after week 20 of pregnancy.

Untreated pre-eclampsia is dangerous because it can harm the mother’s organs and lead to seizures. If these seizures, called eclampsia, aren’t treated right away, they are usually fatal for a woman and her baby. Pre-eclampsia or eclampsia can also lead to low birth weight in the baby, premature delivery, which can cause health problems in the baby, or placental abruption, in which the placenta comes loose from the uterus before the baby is born, causing bleeding.

Pre-eclampsia can also progress to HELLP syndrome, another life-threatening condition. It is called HELLP because it is defined by the breakdown of red blood cells (Hemolysis), Elevated Liver enzymes and a Low Platelet count.

One out of every 200 women with untreated pre-eclampsia progresses to eclampsia. Most cases of eclampsia occur in the third trimester of pregnancy or within 4 days after delivery. Rarely, it may develop up to 6 weeks after delivery.

Pre-eclampsia sometimes causes symptoms that are very similar to those of normal pregnancy. Some women with pre-eclampsia may have no symptoms at all. That is why it is important to regularly attend all prenatal checkups. During the checkup, the healthcare practitioner will do a physical exam and perform laboratory tests to look for the “silent” signs of pre-eclampsia, like high blood pressure and protein in the urine.

If left untreated, pre-eclampsia can lead to serious and life-threatening complications for a mother and her baby.

Possible complications include:

• Seizure (eclampsia)
• Liver rupture
• Stroke
• Low birth weight in the baby
• Placental abruption (the placenta comes loose from the uterus before the baby is born and causes bleeding)

Women with a history of pre-eclampsia are more likely to develop:

• Heart disease
• Diabetes
• Kidney disease

Researchers are still trying to establish the exact cause of pre-eclampsia. However, it is associated with certain risk factors. These include:

• A past pregnancy with pre-eclampsia
• A family history of pre-eclampsia
• Being pregnant for the first time
• Being older than age 35 at the time of pregnancy
• Obesity
• Carrying multiple babies
• A history of other conditions, including chronic high blood pressure, migraine headaches, type 1 or type 2 diabetes, kidney disease, a hypercoagulable state (increased tendency for blood to clot), antiphospholipid syndrome, or lupus

Proteinuria in pregnancy signs and symptoms

Pre-eclampsia is a serious complication of pregnancy that can develop with no obvious symptoms. If symptoms are present, they may seem similar to those experienced during normal pregnancy. For example, weight gain and swelling are pre-eclampsia symptoms that also occur during normal pregnancies. High blood pressure is a sign of pre-eclampsia that typically goes unnoticed until a healthcare practitioner detects it during a routine pre-natal visit.

If you have symptoms associated with pre-eclampsia or notice sudden changes in your pregnancy, it is important that you let your healthcare provider know right away. He or she will look for other signs of pre-eclampsia and help monitor your symptoms. Untreated pre-eclampsia is a serious condition that can be fatal for you and your baby. Be sure to attend all pre-natal checkups and seek medical attention if symptoms arise.

Symptoms of pre-eclampsia may include:

• Sudden weight gain of more than 2 pounds in a week
• Sudden face and hand swelling (edema)
• Persistent headaches
• Vision changes: temporary loss, blurry vision, flashing light sensations, or light sensitivity
• Bluish skin resulting from poor circulation
• Nausea or vomiting, especially if it suddenly appears after mid-pregnancy
• Decreased urine output
• Shortness of breath caused by fluid in the lungs or increased blood pressure
• Shoulder pain or stomach pain or pinching, especially in the upper right side of your abdomen or when laying on your right side—may indicate liver problems

Some signs of pre-eclampsia that may be detected during a physical exam include:

• Elevated blood pressure
• Unusually strong leg reflexes (i.e., when a healthcare practitioner taps your knee with a rubber hammer)

Blurred vision, severe headaches, abdominal pain, and shortness of breath are all serious symptoms of pre-eclampsia. If you have any of these symptoms you should seek immediate medical care.

Proteinuria in pregnancy diagnosis

To diagnose preeclampsia, you have to have high blood pressure and one or more of the following complications after the 20th week of pregnancy:

• Protein in your urine (proteinuria)
• A low platelet count
• Impaired liver function
• Signs of kidney problems other than protein in the urine
• Fluid in the lungs (pulmonary edema)
• New-onset headaches or visual disturbances

Previously, preeclampsia was only diagnosed if high blood pressure and protein in the urine were present. However, experts now know that it’s possible to have preeclampsia, yet never have protein in the urine.

A blood pressure reading in excess of 140/90 mm Hg is abnormal in pregnancy. However, a single high blood pressure reading doesn’t mean you have preeclampsia. If you have one reading in the abnormal range — or a reading that’s substantially higher than your usual blood pressure — your doctor will closely observe your numbers.

Having a second abnormal blood pressure reading four hours after the first may confirm your doctor’s suspicion of preeclampsia. Your doctor may have you come in for additional blood pressure readings and blood and urine tests.

Tests that may be needed

If your doctor suspects preeclampsia, you may need certain tests, including:

• Blood tests. Your doctor will order liver function tests, kidney function tests and also measure your platelets — the cells that help blood clot.
• Urine analysis. Your doctor will ask you to collect your urine for 24 hours, for measurement of the amount of protein in your urine. A single urine sample that measures the ratio of protein to creatinine — a chemical that’s always present in the urine — also may be used to make the diagnosis.
• Fetal ultrasound. Your doctor may also recommend close monitoring of your baby’s growth, typically through ultrasound. The images of your baby created during the ultrasound exam allow your doctor to estimate fetal weight and the amount of fluid in the uterus (amniotic fluid).
• Nonstress test or biophysical profile. A nonstress test is a simple procedure that checks how your baby’s heart rate reacts when your baby moves. A biophysical profile uses an ultrasound to measure your baby’s breathing, muscle tone, movement and the volume of amniotic fluid in your uterus.

Proteinuria in pregnancy treatment

The most effective treatment for preeclampsia is delivery. You’re at increased risk of seizures, placental abruption, stroke and possibly severe bleeding until your blood pressure decreases. Of course, if it’s too early in your pregnancy, delivery may not be the best thing for your baby.

If you’re diagnosed with preeclampsia, your doctor will let you know how often you’ll need to come in for prenatal visits — likely more frequently than what’s typically recommended for pregnancy. You’ll also need more frequent blood tests, ultrasounds and nonstress tests than would be expected in an uncomplicated pregnancy.

Medications

Possible treatment for preeclampsia may include:

• Medications to lower blood pressure. These medications, called antihypertensives, are used to lower your blood pressure if it’s dangerously high. Blood pressure in the 140/90 millimeters of mercury (mm Hg) range generally isn’t treated. Although there are many different types of antihypertensive medications, a number of them aren’t safe to use during pregnancy. Discuss with your doctor whether you need to use an antihypertensive medicine in your situation to control your blood pressure.
• Corticosteroids. If you have severe preeclampsia or HELLP syndrome, corticosteroid medications can temporarily improve liver and platelet function to help prolong your pregnancy. Corticosteroids can also help your baby’s lungs become more mature in as little as 48 hours — an important step in preparing a premature baby for life outside the womb.
• Anticonvulsant medications. If your preeclampsia is severe, your doctor may prescribe an anticonvulsant medication, such as magnesium sulfate, to prevent a first seizure.

Bed rest

Bed rest used to be routinely recommended for women with preeclampsia. But research hasn’t shown a benefit from this practice, and it can increase your risk of blood clots, as well as impact your economic and social lives. For most women, bed rest is no longer recommended.

Hospitalization

Severe preeclampsia may require that you be hospitalized. In the hospital, your doctor may perform regular nonstress tests or biophysical profiles to monitor your baby’s well-being and measure the volume of amniotic fluid. A lack of amniotic fluid is a sign of poor blood supply to the baby.

Delivery

If you’re diagnosed with preeclampsia near the end of your pregnancy, your doctor may recommend inducing labor right away. The readiness of your cervix — whether it’s beginning to open (dilate), thin (efface) and soften (ripen) — also may be a factor in determining whether or when labor will be induced.

In severe cases, it may not be possible to consider your baby’s gestational age or the readiness of your cervix. If it’s not possible to wait, your doctor may induce labor or schedule a C-section right away. During delivery, you may be given magnesium sulfate intravenously to prevent seizures.

If you need pain-relieving medication after your delivery, ask your doctor what you should take. NSAIDs, such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve), can increase your blood pressure.

After delivery, it can take some time before high blood pressure and other preeclampsia symptoms resolve.

Proteinuria in children

Proteinuria is a common laboratory finding in children. Proteinuria in children can be identified as either a transient proteinuria or a persistent proteinuria and can represent a benign condition or a serious kidney disease ¹⁾. Transient (functional) proteinuria is temporary. Transient proteinuria can occur with fever, exercise, stress, or cold exposure, and it resolves when the inciting factor is removed. If your doctor finds protein in your child’s urine, it means your child’s kidneys may not be working as they should, possibly because of inflammation (swelling). Sometimes infection or chemicals damage the kidneys, and this makes protein show up in the urine. If your child has an infection, the proteinuria will go away once the infection is treated.

Proteinuria doesn’t cause pain. When a lot of protein is in the urine, the level of protein in the blood may go down. This can cause swelling in your child’s eyelids, ankles and legs. High blood pressure is another sign of this problem.

Orthostatic proteinuria is the most common type of transient proteinuria in some older children and teenagers, especially in adolescent males. Orthostatic proteinuria is a benign condition without clinical significance. The word orthostatic means “upright.” The condition is called “orthostatic proteinuria” because protein goes into the urine only when the child is standing up. Children who have orthostatic proteinuria have no kidney damage, but for some unknown reason, they lose protein into the urine during the day when they are active. At night, while they sleep, their kidneys don’t let any protein into the urine. Your doctor diagnoses this harmless condition by checking 2 urine samples. The first is collected in the morning, right after your child gets up. The second sample is collected throughout the day. The samples are kept in separate containers. If your child has transient proteinuria (orthostatic proteinuria), the morning sample won’t have protein in it, but the urine collected during the day will have protein in it.

How is proteinuria in children diagnosed?

Your doctor may want to recheck your child’s urine for protein because it will often go away on its own (transient proteinuria). If it is still high, your doctor may ask you to collect a 24-hour urine sample from your child. Directions for doing this are at the end of this handout. A 24-hour urine collection lets your doctor measure the amount of protein in the urine more accurately. Your doctor may also do some blood tests.

How is proteinuria in children treated?

If your child has orthostatic proteinuria or only small amounts of protein in the urine, no treatment is needed. If there is a large amount of protein in your child’s urine and your child has swelling of the legs and eyelids, your doctor may send your child to a kidney specialist (called a nephrologist). The nephrologist may perform a kidney biopsy. A small piece of kidney tissue is taken out using a needle, and looked at under a microscope. When your doctor finds out what causes the protein in your child’s urine, he or she can treat the problem.

Proteinuria causes

Your kidneys filter waste products from your blood while retaining what your body needs — including proteins. However, some diseases and conditions allow proteins to pass through the filters of your kidneys, causing protein in urine.

Conditions that can cause a transient proteinuria or temporary rise in the levels of protein in urine, but don’t necessarily indicate kidney damage, include:

• Dehydration
• Emotional stress
• Exposure to extreme cold
• Fever
• Strenuous exercise

Diseases and conditions that can cause persistently elevated levels of protein in urine, which might indicate kidney disease, include:

• Amyloidosis (buildup of abnormal proteins in your organs)
• Certain drugs, such as nonsteroidal anti-inflammatory drugs
• Chronic kidney disease
• Diabetes
• Endocarditis (an infection of the inner lining of the heart)
• Focal segmental glomerulosclerosis (FSGS)
• Glomerulonephritis (inflammation in the kidney cells that filter waste from the blood)
• Heart disease
• Heart failure
• High blood pressure (hypertension)
• Hodgkin’s lymphoma (Hodgkin’s disease)
• IgA nephropathy (Berger’s disease) (kidney inflammation resulting from a buildup of the antibody immunoglobulin A)
• Kidney infection (pyelonephritis)
• Lupus
• Malaria
• Multiple myeloma
• Nephrotic syndrome (damage to small filtering blood vessels in the kidneys)
• Orthostatic proteinuria (urine protein level rises when in an upright position)
• Preeclampsia
• Pregnancy
• Rheumatoid arthritis (inflammatory joint disease)
• Sarcoidosis (collections of inflammatory cells in the body)
• Sickle cell anemia

Proteinuria symptoms

Most people with proteinuria or kidney disease do not have symptoms unless the disease is very advanced. Laboratory testing is the only way to know for sure if someone has protein in the urine. Several health organizations recommend regular urine tests for people at risk for chronic kidney disease. There are frequently no symptoms associated with proteinuria, especially in mild cases. Large amounts of protein may cause urine to appear foamy. Significant loss of protein from the blood can affect the body’s ability to regulate fluids, which can lead to swelling in the hands, feet, abdomen, and face (edema). When symptoms are present, they are usually associated with the condition or disease causing proteinuria.

You may feel:

• Swelling
• Shortness of breath
• Needing to urinate more often
• Hiccups
• Fatigue (feeling tired)
• Trouble sleeping
• Nausea and vomiting
• Dry, itchy skin.

Proteinuria test

The goals of testing for proteinuria include screening individuals who may be at risk, detecting the condition, determining its underlying cause, evaluating the type and quantity of protein being released, and evaluating kidney function. If proteinuria is detected, the person will be monitored at intervals to see if it resolves or becomes worse. Both urine and blood tests will be ordered to evaluate proteinuria.

Laboratory tests

Screening for protein in the urine may be performed as part of a general health exam or as part of a check-up for an individual who is known to have a condition that may cause proteinuria. Some screening tests include:

• Urine protein – detects the presence of any type of protein that may be in the urine. It can be performed alone on a random urine sample or as part of a urinalysis.
• Urinalysis – an evaluation of a urine sample for several different substances that may be in the urine, including protein. This test may be used as part of a general health exam.
• Urine albumin (microalbumin) – a sensitive test that is used to monitor people with diabetes for small amounts of albumin, the main blood protein, in the urine. Over time, diabetes can begin to affect kidney function and this test is an early indicator that diabetes has caused some kidney damage. The American Diabetes Association recommends that people diagnosed with type 2 diabetes be screened annually for low levels of albumin in the urine (microalbuminuria) and that type 1 diabetics be tested 5 years after diagnosis and annually thereafter.

A positive result on a screening test may be followed by further urine tests to determine how much protein and what type of protein is being lost in the urine:

• Urine albumin, 24 hour urine – measures the amount of albumin that is escaping into the urine within that time frame. This test may give the healthcare practitioner a better assessment as to the degree of kidney damage.
• Urine albumin/creatinine ratio – as an alternative to collecting urine for 24 hours, a random urine sample may be used. In this case, creatinine is also measured. Creatinine is a substance that is released into the urine at a steady rate. When both protein and creatinine are measured in a random sample, a urine albumin/creatinine ratio can be calculated. This calculation corrects for the amount of creatinine in the random sample, more accurately reflecting how much albumin has been lost in the urine.
• Urine protein, 24-hour urine – measures the amount of protein released in the urine in a 24-hour period; this is a more accurate assessment of the degree of proteinuria than a random urine test.
• Urine protein/creatinine ratio (UPCR) – measures protein and creatinine in a random sample and corrects it for the amount of creatinine, similar to the urine albumin/creatinine ratio
• Urine protein electrophoresis – a test used to determine the different types and relative concentrations of protein present in the urine. A urine test specifically for detecting the presence of Bence-Jones protein is sometimes used when multiple myeloma is suspected.
• When the protein electrophoresis shows an abnormality, an immunofixation test may be performed to quantify the abnormal protein, in addition to an immunoassay evaluation for free light chains.

In addition to testing urine, there are several other tests that may be used to evaluate kidney function and/or assess the nature of the protein present in the urine. These tests may be done at the same time as urine protein screening or in follow-up. The tests include:

• BUN (Blood Urea Nitrogen) and Creatinine – blood tests used to evaluate kidney function; urea and creatinine are nitrogen-containing waste products that healthy kidneys move from the blood to the urine. If the kidneys are not functioning properly, urea and creatinine will remain in the blood and the levels will increase. (Note: Although creatinine may be measured in urine samples, a blood sample is also measured to be included as part of the evaluation.)
• eGFR (estimated Glomerular Filtration Rate) – uses a blood creatinine level along with age and values assigned for sex and race to calculate the estimated rate of urine filtration; the eGFR rate decreases with progressive kidney damage.
• Creatinine clearance – measures creatinine in a 24-hour urine sample and a blood sample to calculate the amount of creatinine that has been cleared from the blood and passed into the urine; this calculation allows for a general evaluation of kidney function based on the rate of creatinine excretion from the body.
• Total Protein – a blood test that measures all of the protein in the serum
• Albumin – a blood test that measures the concentration of albumin (the most prevalent protein in blood serum)
• Serum protein electrophoresis – determines the types and relative amounts of protein in blood serum and is compared to the urine electrophoresis pattern to determine if blood is the source of the protein seen in the urine
• Serum Free Light Chains – a blood test used to help diagnose and monitor conditions associated with an increased production of free light chains such as multiple myeloma

A healthcare practitioner may also order a kidney biopsy. In a kidney biopsy, a small sample of the kidney tissue is examined with a microscope by a pathologist and may be used to look for evidence of kidney disease or damage. (For more, read the article on Anatomic Pathology.) Additional studies using electron microscopy, immunohistochemistry, and immunofluorescence may also be performed to further evaluate a kidney biopsy.

Non-Laboratory Tests

• Imaging scans of the kidney may be performed to detect the presence and determine the severity of kidney disease or damage.
• Blood pressure may be measured as part of an investigation of the cause of proteinuria. It is frequently monitored in people who have hypertension or are at risk of developing it.

Proteinuria treatment

Different underlying conditions can cause proteinuria. The treatment of proteinuria focuses on controlling the underlying condition causing proteinuria and minimizing its progression. Therefore, treatment for each condition is likely to be different. For example, someone with diabetes should carefully monitor and control their blood sugar levels to help to preserve kidney function. Someone with high blood pressure (hypertension) will need to control blood pressure to prevent progressive kidney damage. Pre-eclampsia-related proteinuria during pregnancy will be carefully monitored and usually resolves once the baby is born. Sometimes medications, such as blood pressure medication, will be prescribed depending on the severity of the preeclampsia.

Proteinuria diet

People with persistent proteinuria and especially those with reduced kidney function may receive recommended dietary changes from their healthcare provider, such as minimizing intake of protein or cholesterol-rich food products. No treatment may be necessary for mild or transient proteinuria.