Proteinuria is the presence of excessive proteins in urine.
In healthy individuals, urine contains only small amounts of protein. The main part of the nephron (the functional unit of the kidney) known as the glomerulus filters the blood in order to excrete the waste products. Normally, proteins do not get into urine as they have a high molecular weight and are too large to pass the barrier. However, some proteins which have a lower molecular weight may pass the barrier. Later most of them are reabsorbed in the proximal tubule of the nephron. Small quantities of protein are still excreted with the urine.
Excessive excretion of the proteins in urine may be caused by a large number of different disorders and be of different severity.
Normal amount of protein in urine
The normal daily loss of protein in urine is less than 150 mg (for children less than 140mg/m2/day), and albumin loss is less than 30 mg/day.
Pathophysiology of proteinuria
Tubular proteinuria is caused by the damage of the tubule-intestinal part of the kidney when the proteins of low molecular weight are not reabsorbed in the proximal tubules. Tubular proteinuria is less than 2 g/day.
Glomerular proteinuria may be transient, orthostatic (when the kidneys are healthy) or caused by the damaged glomeruli.
Transient proteinuria occurs in otherwise healthy individuals when they exercise a lot, experience high fever or are exposed to extreme temperatures. The protein loss is not larger than 1 g/day and the protein is not detected in urine when the urinalysis is repeated.
Orthostatic proteinuria of less than 1 g/day is usually detected in the evening in healthy tall individuals younger than 30 years who are standing or moving a lot during the day. In the morning in these persons, there is no protein in urine samples.
Various diseases may damage the glomeruli and cause proteinuria due to impaired kidney filtration. The protein excretion of less than 3.5 g/day is known as non-nephrotic proteinuria, and when the protein loss is more than 3.5 g/day nephrotic-range proteinuria is diagnosed.
Postglomerular proteinuria is caused by the secretion of the protein due to infection or renal calculi in the upper and lower urinary tract.
Overflow proteinuria occurs when abnormal proteins of low molecular weight (such as Bence-Jones protein, light chains amyloid, myoglobin, etc.) are being produced in the body in large amounts. The tubules are not able to reabsorb all of these proteins and proteinuria occurs. At the same time, these proteins influence toxic on the tubules and cause acute kidney injury.
Classification and causes
- Minimal Proteinuria (< 0.5 g/day)
- Following exercise or in highly concentrated urine, in healthy persons
- Fever, severe emotional stress or extreme temperature
- Orthostatic/postural proteinuria
- Renal tubular dysfunction, including genetic and drug-induced
- Polycystic kidneys
- Lower urinary tract infections
- Hemoglobinuria with severe hemolysis
- Moderate Proteinuria (0.5–3 g/day)
- Moderate chronic glomerulonephritis
- Congestive heart failure
- Mild diabetic nephropathy
- Multiple myeloma
- Preeclampsia or eclampsia
- Severe Proteinuria (> 3.5 g/day)
- Acute glomerulonephritis
- Severe chronic glomerulonephritis
- Lipoid nephrosis
- Severe diabetic nephropathy
- Renal amyloidosis
- Lupus nephritis
- Nonrenal causes of proteinuria
- Severe anemias and leukemia
- Abdominal tumors
- Intestinal obstruction
- Cardiac disease
- Poisoning from turpentine, phosphorus, mercury, sulfosalicylic acid, lead, phenol, opiates, and drug therapy
Microalbuminuria is an excretion of 30-300 mg of albumin per day. Microalbuminuria is usually detected as an early sign of nephropathy in individuals with diabetes mellitus, arterial hypertension, and other cardiovascular diseases.
Bence-Jones protein is an immunoglobulin light chain (paraprotein). This type of proteins is characteristic for multiple myeloma, although it may also be detected in individuals with chronic leukemia, adult Fanconi syndrome, hyperparathyroidism, osteomalacia, osteosarcoma, cancer metastases to bone, and hypertension.
- The sulfosalicylic acid test is performed to detect the presence of the protein in the urine. 3 drops of sulfosalicylic acid are added to 1 ml of the urine. The protein in urine results in the cloudiness of the urine;
- Paper strip method – paper strip is dipped in the urine sample. The protein in the urine causes color change from yellow to blue;
- Urinalysis is an analysis of the urine to detect various substances in urine and the protein;
- 24-hour urine is collected to evaluate the protein/albumin loss per 24 hours;
- Urine albumin/creatinine ratio and urine protein/creatinine ratio are defined as the correlation of albumin/protein, respectively, to creatinine measured in a random urine sample;
- Urine protein electrophoresis allows to determine the types of protein present in urine;
- Microalbuminuria may be detected only by highly sensitive immunoassays;