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Proteinuria is an abnormally high amount of protein in the urine. What causes this, and what can you do about it?
Proteins in the blood, like albumin and immunoglobulin, have many crucial functions such as helping in coagulation, creating a balance of body fluids, and fighting infection. Every person should know that the kidneys are mainly responsible for the function of removing waste from blood. The kidneys remove wastes from the protein-rich blood through millions of tiny filtering screens called glomeruli. Because these proteins are too big to pass the glomeruli, they normally shouldn’t be found in the urine! Besides the size barrier, the glomeruli are also negatively charged, so they repel negatively charged proteins. [1]

There is also a charge barrier. Several types of research done in the past have shown that, in the situation where the glomeruli are damaged, proteins of various sizes pass through them and are excreted in the urine. That’s why if a lot of protein is found in a patient’s urine, a serious kidney disease might be the problem. The big problem is that proteinuria doesn't cause pain, which represents a big diagnostic problem!

Possible Symptoms Of Proteinuria

Normally there are no symptoms of proteinuria, which is a big diagnostic problem because patients contact their doctor very late!
 
It is important to know that protein is detected by a routine urine test. A simple test with a dipstick can detect very small amounts of protein, so that a positive test may not mean there is any serious problem with the kidneys.
 
If the amount of protein in the urine is very high, a condition called nephrotic syndrome may develop. Nephrotic syndrome causes water to build up in the body. The extra water can cause [2]:
  • Ankle swelling
  • Swelling in the hands
  • Swelling around the eyes
  • Swelling of the tummy
  • Breathlessness due to water around the lungs
  • Foamy urine

Possible Causes Of Proteinuria

Every patient should know that protein in the urine can be a marker of almost any type of kidney disease, which means that there is no one specific test for it! Therefore, different tests are always needed if the cause of proteinuria is to be confirmed. These are the most common causes [3]:
  • High blood pressure
  • Infection
  • Reflux nephropathy
  • Diabetes
  • Glomerulonephritis
  • Minimal change nephritis

Types Of Proteinuria

If we look at a number of proteins found in urine, the following five types of proteinuria exist. They are distinguished by milligrams (mg) of protein measured during a 24-hour urine collection [3]:
  • 1. Microalbuminuria

30–150 mg

  • 2. Mild

150–500 mg

  • 3. Moderate

500–1000 mg

  • 4. Heavy

1000–3000 mg

  • 5. Nephrotic range

more than 3500 mg

Several studies done in the past have concluded that, as kidney disease progresses, more protein enters the urine. People with nephrotic-range proteinuria typically have extensive glomeruli damage and usually develop nephrotic syndrome.

Pathophysiology

Several experts suggest that, if we look at the localization of the pathological process, there are 3 basic types of proteinuria — glomerular, tubular, and overflow proteinuria. [4]
  • Glomerular Proteinuria

What exactly is the glomerular filtration barrier? This is barrier composed of the endothelial cell, the basement membrane, and the epithelial cell foot processes. Proteinuria occurring in glomerular disease is due to increased filtration of albumin and other macromolecules across the glomerular basement membrane. This occurs because of changes in both the charge and size selectivity of the glomerular barrier. It is important to know that, in glomerular disease, the injury to the glomerular basement membrane causes proteinuria due to a loss in negative charge as well as from an increase in the number of larger non-selective pores. Glomerular diseases are also accompanied by disruption and loss of the epithelial foot process covering of the basement membrane.  
  • Tubular Proteinuria

Several types of research done in the past have shown that the low molecular weight molecules such as microglobulin, amino acids, and immunoglobulin light chains which have a molecular weight of about 25000 (albumin is 69000), are easily filtered across the basement membrane and then completely reabsorbed by the proximal tubular cells. But, the problem is that there is a variety of diseases that produce tubular and interstitial injury and damage the tubular reabsorption of these molecules.
  • Overflow Proteinuria

It is proven that increased excretion of low molecular weight proteins might be seen in different conditions where there is significantly increased production of these proteins. One such condition is for example, a multiple myeloma.  

Risks For Developing Proteinuria

People with diabetes, hypertension, or certain family backgrounds are at risk for proteinuria. [3, 5]
  • Diabetes
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.
  • High blood pressure
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 four times more likely than Caucasians to develop hypertension-related kidney failure. High blood pressure is the leading cause of kidney failure among African Americans.
  • High-risk factors
Other groups at risk for proteinuria are American Indians, Hispanic Americans, 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.
  • Other risk factors
Other risk factors include Amyloidosis, protein deposits associated with chronic disease, focal Glomerulonephritis, IgA nephropathy, mesangial proliferation and other.

What Exactly Is Orthostatic Proteinuria?

Many patients are confused because they’ve heard the term orthostatic proteinuria but don’t know exactly what it is! This benign condition occurs in about 3 to 5 percent of adolescents and young adults. [6] This condition is characterized by increased protein excretion in the upright position but normal protein excretion when the patient is supine. To diagnose orthostatic proteinuria, split urine specimens are obtained for comparison and the daytime specimen typically has an increased concentration of protein, with the nighttime specimen having a normal concentration. Patients with true glomerular disease have reduced protein excretion in the supine position, but it will not return to normal, as it will with orthostatic proteinuria.

Isolated Proteinuria

There is also one entity called isolated proteinuria: a proteinuria patient with normal renal function and no evidence of systemic disease that might cause renal malfunction, normal urinary sediment, and normal blood pressures is considered to have isolated proteinuria. [7] It could be very difficult to explain this type of condition and it is proven that protein excretion is usually less than 2 g per day. Isolated proteinuria with urinary protein excretion of more than 2 g per day is rare and usually signifies glomerular disease.

What Are The Complications Of Proteinuria?

Many people with proteinuria turn out to have minor kidney disease with no problems in the long term, but, unfortunately,  some kidney disease can progress to kidney failure. The most common complications of proteinuria are:
  • High blood pressure
There is no doubt that kidney disease commonly causes high blood pressure. This increases the risk of further kidney disease, and also the risk of heart attack and stroke. That’s why drugs may be needed to control the blood pressure.
  • High cholesterol
In nephrotic syndrome, high levels of cholesterol may be found in the blood. If the cholesterol level is high over a period of years there is an increased risk of a heart attack. The good thing is that, if the nephrotic syndrome is cured quickly, the cholesterol levels will go down on its own. However, in some cases where a rapid cure is not possible, drugs to reduce the cholesterol may be needed.

Treatment Of Proteinuria

Proteinuria is not a specific disease, so its treatment depends on identifying and managing its underlying cause. For example, if the patient has diabetes, hypertension, or both, the first goal of treatment should always be to control your blood glucose and blood pressure.[9]

Sometimes a doctor may prescribe a medicine from a class of drugs called ACE (angiotensin-converting enzyme). [8]  

People who have high blood pressure and proteinuria but not diabetes also benefit from taking an ACE inhibitor or ARB (angiotensin receptor blockers) [10]. Their blood pressure should be maintained below 130/80. A doctor may also prescribe a diuretic in addition to your ACE inhibitor or ARB.

It is extremely important that anyone with proteinuria is monitored over time. However for most people who have a lower level of proteinuria, the right thing is simply to monitor urine tests, blood pressure and kidney function over a prolonged period.

In patients with chronic disease such as diabetes and high blood pressure, it is essential to prevent the progressive kidney damage that is causing the proteinuria, because untreated chronic kidney disease can lead to kidney failure.

In mild or temporary proteinuria, no treatment may be necessary.