Proteinuria

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.

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.
• Obesity.
• 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.