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The kidneys contain special filters called glomeruli to filter out toxic substances and waste products from the blood stream and transfer them to the urine so that they can be removed from the body. The glomeruli also keep substances that your body needs, such as proteins, from being filtered out of the body. Proteinuria usually reflects increased permeability of the glomeruli to these large particles. Sometimes patients have obvious symptoms, such as edema (swelling), blood in the urine (hematuria), or pus in the urine (pyuria), but in many cases there are no symptoms.

Normal urinary protein excretion should be less than 150 mg per day. Protein excretion above 150 mg per day is called proteinuria; proteinuria that persists beyond a single measurement should not be ignored and must be evaluated by a physician.

Proteinuria is detected by analysis of the urine (urinalysis). It is important to differentiate between relatively benign causes of proteinuria and less common causes that require consultation with a doctor who specializes in diseases of the kidneys (nephrologist).

When there are no symptoms and the presence of proteinuria is discovered incidentally by use of a dipstick during routine urinalysis, two questions need to be answered:

1. How much protein is being excreted?
2. Under what conditions is protein excreted?

HOW MUCH PROTEIN IS BEING EXCRETED? ? The rate of protein excretion is measured with a 24-hour urine collection. A relatively accurate estimate can be obtained more simply and quickly by calculating a specific ratio (the total protein-to-creatinine) on a random urine specimen.

Most patients with benign forms of isolated proteinuria excrete less than 1 to 2 grams/day. In patients with a more serious form of primary disease of the glomeruli, protein excretion is often greater than 3 grams/day. Patients with heavy proteinuria may have a constellation of findings called the nephrotic syndrome. ( See "Patient information: The nephrotic syndrome" ).

UNDER WHAT CONDITIONS IS PROTEIN EXCRETED? ? Proteinuria can be divided into three categories: transient (or intermittent), orthostatic, and persistent.

Transient proteinuria ? Transient proteinuria is by far the most common form, occurring in 4 percent of men and 7 percent of women on a single examination. Transient proteinuria resolves on subsequent examinations in almost all patients. Stresses such as fever and exercise may be responsible for this type of transient increase in protein excretion. For example, with marked exercise, protein excretion can exceed 1.5 mg/minute in normal individuals (which is the equivalent of over 2 g/day if sustained).

Orthostatic proteinuria ? Orthostatic proteinuria primarily occurs in adolescents. A patient's protein excretion is increased in the upright position, but normal when the patient is lying down (less than 50 mg per eight hours). Orthostatic proteinuria is present in 2 to 5 percent of adolescents, but is unusual in people over the age of 30. It is not known why orthostatic proteinuria occurs, but it is thought that it might be due to an exaggeration of the body's normal response to changes in position, a subtle abnormality in the glomeruli, or an exaggerated response of the circulatory system to postural changes.

Orthostatic proteinuria is diagnosed by obtaining a "split" urine collection in which two specimens are obtained: one while you are upright and one, at night, while you are lying down. Orthostatic proteinuria typically disappears with age, and studies have found that kidney function remains normal in these patients even after a 50 year follow-up.

Persistent proteinuria ? In contrast to transient and orthostatic proteinuria, persistent proteinuria is more likely to reflect underlying kidney disease or systemic disorder. As one example, congestive heart failure is often associated with mild proteinuria. Other patients with proteinuria may have an underlying glomerular disease (disease of the glomeruli), which may be primary glomerular disease, such as focal glomerulosclerosis or membranous nephropathy, or secondary glomerular disease (as a result of another disease), such as diabetic nephropathy.

EVALUATION ? A number of steps will be taken to evaluate the presence of protein in urine ( show figure 1A-1B ). When a urinalysis is positive for protein, the urine is examined under a microscope to see if there are cells, crystals, bacteria,, or structures called casts. If nothing is found, a second and, possibly, third urinalysis should be performed. As mentioned above, transient proteinuria is common, and, in almost all patients, subsequent urine tests are normal.

Persistent proteinuria can be evaluated with a 24-hour urine collection or by calculating the total protein-to-creatinine ratio in a random urine sample. As mentioned above, the 24-hour collection should be split into upright and lying down (supine) specimens in people under the age of 30 in whom orthostatic proteinuria is a consideration. Blood tests that investigate kidney function will also be performed.

A careful medical history is also taken, looking for diabetes mellitus, congestive heart failure, or a prior history of kidney disease. If the proteinuria persists and the history is not helpful, an ultrasound examination should be performed to evaluate the possibility that there are anatomic abnormalities of the kidney. Patients with persistent proteinuria, whatever the cause, should be referred to a nephrologist for decisions regarding further management.

A renal biopsy is generally performed in a patient with persistent mild proteinuria (less than 2 grams/day) only if there is some sign of progressive disease, such as increasing protein excretion, high blood pressure, or evidence by blood tests that the kidney is not functioning properly. Most nephrologists perform a biopsy in patients with higher degrees of proteinuria (2 to 3 grams/day or more).

TREATMENT AND PROGNOSIS OF PROTEINURIA ? Transient and orthostatic proteinuria are benign conditions and no treatment is needed. In those patients with persistent proteinuria, the underlying condition causing the proteinuria may be treated.

Patients with persistent isolated proteinuria, that is not associated with decreased kidney function or a systemic disease, typically follow a mild course even without specific therapy. Many nephrologists would treat such patients with an angiotensin converting enzyme (ACE) inhibitor, a commonly used antihypertensive drug that is well tolerated by most patients.

Progression to kidney failure is more likely to occur in patients with proteinuria greater than 3 grams/day. The treatment is specific to the underlying cause, in addition to administration of an ACE inhibitor.

WHERE TO GET MORE INFORMATION ? Your doctor is the best resource for finding out important information related to your particular case. Not all patients with proteinuria are alike, and it is important that your situation is evaluated by someone who knows you as a whole person.

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