Protein is an essential substance of the body and is mainly made up of amino acids. It performs various key functions in the body; they keep our immunity system strong enough to fight common infection, help digestions, carry various substances around the body and in aids in blood clotting. Protein is normally found in the blood system of the body and should not be present in the urine.
The kidneys are made up of millions of tiny filtering systems known as glomeruli. Most proteins are too large to pass through the glomeruli into the urine. The glomeruli are negatively charged, so they repel the negatively charged proteins. Thus, a size and charge barrier keeps protein molecules from entering the urine. But when the glomeruli are damaged, proteins of various sizes pass through them and are excreted in the urine.
Proteinuria is the condition where the protein leaks out from the kidney into the urine and the urine contains an abnormal amount of protein. In early stage of this condition, albumin leaks out first and when the quantity is small and cannot be detected by conventional methods used for urine protein detection, this is called microalbuminuria. When the condition is more advanced, larger molecules other than albumin leak out and we term this state collectively as “proteinuria”.
INCIDENCE AND CLASSIFICATION OF PROTEINURIA
Based on large observational studies, it is estimated that approximately 11.7% of the adult population in United States have abnormal urine albumin excretion. Among the adults, the prevalence of albuminuria varies by age and presence or absence of diabetes . The prevalence is approximately 30% in adults with age 70 years: 26.6% with microalbuminuria and 3.7% with albuminuria.
At all ages, the prevalence is higher among individuals with diabetes. Among individuals with a history of diabetes, the prevalence of microalbuminuria and albuminuria is 43.2% and 8.4%, respectively, at age 70 years. Among individuals without a history of diabetes the prevalence of microalbuminuria and albuminuria is 24.2% and 3.0%, respectively, at age 70 years.
The severity of proteinuria is determined by the extent of protein leak which is measured by milligrams (mg) or grams (g) of protein measured during a 24-hour urine collection. This can be broadly categorized into :
• Microalbuminuria (30–150 mg)
• Mild (150–500 mg)
• Moderate (500–1000 mg)
• Heavy (1000–3000 mg)
• Nephrotic range (more than 3000 mg)
As the kidney disease progresses, more protein enters the urine. Patients with nephrotic-range proteinuria typically have extensive glomeruli damage and usually develop generalized swelling and this condition is known as nephrotic syndrome.
Proteinuria is not a disease by itself. However; it is an early and sensitive marker of kidney damage in many types of chronic kidney disease.Normal mean value for urine albumin excretion in adults is approximately 10 mg/day. Urine albumin excretion is increased by physiological variables, such as upright posture, exercise, pregnancy, and fever. Normal mean value for urine total protein is approximately 50 mg/day. Any value more than the normal may be indicative of underlying kidney disease.
Hypertension and diabetes are the two biggest risk factors for proteinuria. Age and weight gain also increase the risk.
The following conditions are the other causes of proteinuria:
1. Primary kidney diseases called glomerulonephritis
2. Autoimmune diseases ( eg systemic lupus erythematosus- SLE)
3. Infection (eg hepatitis)
Patients usually are asymptomatic if the degree of proteinuria is very mild. As more protein leaks out, patients typically complain of foamy or frothy urine. Some patients may describe that as having bubbles in the urine. This occurs because protein changes the surface tension between urine and water.
If the lost in protein via the urine is in large quantities (more than 3g/day), a patient may developed nephrotic syndrome and may complain of swelling of legs, abdominal distension and shortness of breath.
PROGNOSIS AND NATURAL COURSE
Some cases of proteinuria can remain stable for many months and years. However, proteinuria may get more heavy in some cases and cause further kidney injury resulting in kidney failure. This is especially so if it is associated with high blood pressure and diabetes and when the proteinuria is rather heavy (more than 1 gram/day).
The higher the proteinuria, the greater the risk of developing into the advanced stages of chronic kidney disease resulting in kidney failure.
DIAGNOSIS & INVESTIGATIONS
A urine dipstick test is a simple method using a test strip immersed into a urine sample to detect the presence of protein in the urine. However, it only measures the concentration in that specific specimen. The concentration of urine passed varies throughout the day hence the urine dipstick is not a very accurate method. This method also is unable to detect microalbuminuria.
The most accurate method to detect proteinuria and microalbuminuria is by measuring the amount of protein excreted in the urine in a 24-hour period (24 hour Urine Total Protein). Collecting urine for 24 hours can be difficult and inconvenient, so the physician often uses a spot urine test in which one sample of urine is analyzed. Healthy kidneys continually remove creatinine from the blood to maintain a stasis between blood levels and urine levels. The ratio of protein to creatinine in the urine is closely related to the 24 hour proteinuria result and hence provide the physician with a good idea of how much protein is being excreted over 24 hours.
There are many causes of proteinuria and the treatment will depend on the underlying cause and degree of protein leak. A series of investigations may be required to ascertain the cause:
1. Blood test to assess the kidney function, ie. blood creatinine level
2. Ultrasound of the kidneys
3. Kidney biopsy may be indicated in some cases for more specific diagnosis and prognosis
If a person has diabetes, hypertension, or both, the first goal of treatment will be to control blood sugar and blood pressure. People with diabetes should test their blood glucose often, follow a healthy eating plan, take prescribed medicines, and get the amount of exercise recommended by their doctor.
A person with diabetes and high blood pressure may need a medicine from a class of drugs called angiotensin-converting enzyme (ACE) inhibitors or a similar class called angiotensin receptor blockers (ARBs). These medicines have been found to protect kidney function even more than other drugs that provide the same level of blood pressure control as well as reducing the proteinuria. Many patients with proteinuria but without hypertension may also benefit from the use of ACE inhibitors or ARBs. The American Diabetes Association and the American College of Cardiology recommend that people with diabetes keep their blood pressure below 130/80.
Patients who have high blood pressure and proteinuria, but not diabetes, also benefit from taking an ACE inhibitor or ARB. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends that people with kidney disease keep their blood pressure below 130/80. To maintain this target, a person may need to take a combination of two or more blood pressure medicines.
In addition to blood glucose and blood pressure control, the National Kidney Foundation recommends restricting dietary salt and protein. A doctor may refer a patient to a dietitian to help develop and follow a healthy eating plan.
Dr Roger Tan, Consultant Nephrologist
The article above is meant to provide general information and does not replace a doctor's consultation.
Please see your doctor for professional advice.