Proteinuria

Proteinuria is the condition of having an abnormally high amount of protein in the urine. The kidneys filter waste products from the blood and allow them to pass out of the body through the urine. Proteins are usually too large to pass through the kidneys' filters or glomeruli and the body keeps them in the bloodstream to help with many important functions. When the kidneys, specifically the glomeruli, are damaged, protein may  escape into the urine and exit the body. Proteinuria may also result from too much protein in the blood, or the inability of the body to retain the protein as it is filtered. Proteinuria has many causes. Some are benign but some may be very serious.

Other Names

 * Urine protein
 * Urine albumin
 * Albuminuria

Types
There are three types (classifications) of proteinuria:

Glomerular
Glomerular proteinuria results from increased glomerular permeability to protein, usually resulting from glomerular disease. Normal barriers to protein filtration begin in the glomerulus, which contains capillaries that allow fluid and small solutes to pass through its membrane but keeps most proteins from passing into the urine. When the glomeruli are damaged, proteins are able to pass from the bloodstream into the urine.

Tubular
In a normally functioning kidney, the proximal tubules resorb (absorb again) small proteins after they are filtered through the glomerulus. Tubular disease, such as that caused by damage from high blood pressure and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) may affect this process and allow proteins to escape into the urine.

Overflow
Overflow proteinuria is a result of the filtering process of the kidneys being overwhelmed by an overproduction of protein, most commonly from the disease multiple myeloma.

Signs and Symptoms
Large amounts of protein in the urine may cause it to look foamy in the toilet. Also, because the protein has left the body, the blood can no longer soak up enough fluid and there may be swelling in the hands, feet, abdomen, or face. These are signs of very large protein loss. Most commonly, there may be proteinuria without any signs or symptoms.

Causes
There are many causes of proteinuria:
 * Amyloidosis
 * Bacterial pyelonephritis
 * Bladder tumor
 * Congestive heart failure
 * Diabetic nephropathy (Diabetes)
 * Glomerulonephritis
 * Goodpasture syndrome
 * Heavy metal poisoning
 * Hemolytic-Uremic Syndrome
 * Thrombotic microangiopathies
 * Systemic Lupus Erythematosus
 * Malignant hypertension
 * Multiple myeloma
 * Nephrotic syndrome ( various causes)
 * Nephrotoxic drug therapy
 * Polycystic kidney disease
 * Preeclampsia
 * Interstitial nephritis
 * Medullary cystic disease
 * Membranoproliferative GN I
 * Membranoproliferative GN II
 * Membranous nephropathy
 * Necrotizing vasculitis
 * Post-streptococcalGN
 * Rapidly progressive (crescentic) glomerulonephritis
 * Reflux nephropathy
 * Renal vein thrombosis
 * Fibrillary Glomerulonephritis
 * HIV related kidney damage
 * Immunotactoid Glomerulonephritis

Exams and tests
The simplest test for proteinuria is to use a strip of chemically treated paper that will change color when dipped in urine with too much protein. This is called a urine dipstick test. There are many different proteins in the body. The protein most commonly measured in the urine is called albumin. The urine dipstick test is a good screening test. However, protein other than albumin in the urine may give a false negative result and other substances in the urine (blood, infection and certain medications) may give a positive result for protein in the absence of true kidney disease so further testing may be needed when the dipstick test is positive.

A laboratory test that measures the exact amount of protein in the urine over a period of time is a 24-hour urine test. A large plastic container is given to the patient to take home. The patient uses the container every time they urinate during a 24 hour period. The urine is delivered to the laboratory, where it can be analyzed for the content of different chemicals, including protein.

The type of proteinuria may be determined by the amount of protein found in the urine.
 * 0.15 to 2.0 g protein/day indicates mild glomerular disease, tubular disease, or overflow proteinuria.
 * >3.0 g protein/day indicates glomerular disease.

Another test uses a smaller sample of urine to check for Bence-Jones protein in the urine. This is a specific type of protein not normally found in the urine in a significant amount. When present in the urine, a diagnosis of multiple myeloma is likely. Bence-Jones protein in the urine can also (less commonly) indicate a diagnosis of Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, or amyloidosis.

A urine or serum electophoresis can be done to evaluate the specific protein that is being overexcreted.

A sample of the blood can be checked for creatinine and urea nitrogen. These are waste products that healthy kidneys remove from the blood. High levels of creatinine and urea nitrogen in the blood indicate that kidney function is impaired.

Finally, the ratio of urine protein to creatinine in a small sample of urine can be used to estimate the degree of protein excretion at that point in time. This is a useful test to diagnosis and monitor patients with proteinuria or at significant risk of kidney disease because of diabetes or high blood pressure. This test is much simpler than the 24 hour collection of urine and correlates very well with the protein amount over 24 hours. For example, a ratio of protein to creatinine in the urine of 3.7 indicates roughly 3.7 grams of loss of protein over 24 hours.

Treatment
The treatment of proteinuria involves treating the underlying disease process causing damage to the kidney or overproduction of protein as well as preventing further damage to the kidneys. Patients with significant proteinuria are usually referred to a nephrologist (a doctor who specializes in diseases of the kidney) for diagnosis and treatment.

If the proteinuria is a result of kidney damage from diabetes, the first goal of treatment is to control blood glucose and blood pressure. Anyone with diabetes, should test their blood glucose often, follow a healthy eating plan, take all prescribed medicines, and get plenty of exercise. If a patient has diabetes and high blood pressure, they may prescribed a medicine from a class of drugs called ACE (angiotensin-converting enzyme) inhibitors or a similar class called ARBs (angiotensin receptor blockers). These drugs have been found to protect kidney function even more than other drugs that provide the same level of blood pressure control. The American Diabetes Association recommends that people with diabetes keep their blood pressure below 130/80.

People who have high blood pressure and proteinuria but not diabetes also benefit from taking an ACE inhibitor or ARB. Their blood pressure should also be maintained below 130/80. To maintain this target, it may be necessary to take a combination of two or more blood pressure medicines. The doctor may also prescribe a diuretic in addition to an ACE inhibitor or ARB. Diuretics are also called "water pills" because they can increase urination which will help to get rid of excess fluid in the body.

Risks
People with diabetes, hypertension, or certain family backgrounds are at risk for proteinuria. In the United States, diabetes is the leading cause of end-stage renal disease (ESRD), the result of chronic kidney disease. In both type 1 and type 2 diabetes, the first sign of deteriorating kidney function is the presence of small amounts of albumin in the urine, a condition called microalbuminuria. As kidney function declines, the amount of albumin in the urine increases, and microalbuminuria becomes full-fledged proteinuria. Micro albuminuria is now also an independent risk factor for cardiovascular disease.

High blood pressure is the second leading cause of ESRD. Proteinuria in a person with high blood pressure is an indicator of declining kidney function. If the hypertension is not controlled, the person can progress to full renal failure.

African Americans are more likely than Caucasians to have high blood pressure and to develop kidney problems from it, even when their blood pressure is only mildly elevated. In fact, African Americans are six times more likely than Caucasians to develop hypertension-related kidney failure.

Other groups at risk for proteinuria are American Indians, Hispanic/Latinos, Pacific Islander Americans, older people, and overweight people. These at-risk groups and people who have a family history of kidney disease should have their urine tested regularly.

Clinical Trials
There are a number of ongoing clinical trials relating to proteinuria. A list of trials is available [here

Recent discoveries

 * The mechanism of proteinuria and glomerular disease is likely related to the endothelin-1 protein. Several antiproteinuric drugs, including angiotensin-converting-enzyme inhibitors, angiotensin receptor antagonists, statins and certain calcium channel blockers, inhibit the formation of endothelin-1. Research shows that endothelin receptor antagonists (sitaxsentan or bosentan) can reverse proteinuric renal disease and glomerular disease.
 * Angiotensin receptor blocker medicines used in patients with type 2 diabetes and proteinuria are shown to protect the kidneys from further damage as well as lessening the risk of cardiovascular disease.
 * Recent data suggests that the measure of low-grade albuminuria may be a more accurate measure of cardiovascular risk than the traditionally used glomerular filtration rate.

Current research

 * A study is ongoing to evaluate whether ramipril (an ACE inhibitor) and valsartan (an ARB blocker) used together or the two drugs added to furosemide (a diuretic) is more effective at treating proteinuria of more than 1 g/day.
 * The effect of the lipid-lowering drugs rosuvastatin and atorvastatin on urinary protein excretion over a one year period in diabetic patients.
 * The efficacy of different doses of valsartan in the treatment of albuminuria and proteinuria in patients with hypertension and type 2 diabetes is being studied.