Proteinuria

Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein, less than 150 mg/day; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom may also be caused by other conditions). Severe proteinuria can cause nephrotic syndrome in which there is worsening swelling of the body.

Signs and symptoms

Proteinuria often causes no symptoms and it may only be discovered incidentally.

Foamy urine is considered a cardinal sign of proteinuria, but only a third of people with foamy urine have proteinuria as the underlying cause. It may also be caused by bilirubin in the urine (bilirubinuria), retrograde ejaculation, glycosuria, dehydration, a fast urine stream, pneumaturia (air bubbles in the urine) due to a fistula, or drugs such as phenazopyridine (trademarked as 'Pyridium').

Due to disease in the glomerulus
Because of increased quantity of proteins in serum (overflow proteinuria)
Due to low reabsorption at proximal tubule (Fanconi syndrome)

Proteinuria can also be caused by certain biological agents, such as bevacizumab (Avastin) used in cancer treatment. Excessive fluid intake (drinking in excess of 3.79 liters (one gallon) of water per day) is another cause.

Conditions with proteinuria

Proteinuria may be a feature of the following conditions:

Fabry disease
Infections (e.g. HIV, syphilis, hepatitis, poststreptococcal infection, urinary schistosomiasis)
Aminoaciduria
Fanconi syndrome in association with Wilson disease
Hypertensive nephrosclerosis
Interstitial nephritis
Sickle cell disease
Hemoglobinuria
Multiple myeloma
Myoglobinuria
Organ rejection:
Ebola virus disease
Nail–patella syndrome
Familial Mediterranean fever
HELLP syndrome
Systemic lupus erythematosus
Granulomatosis with polyangiitis
Rheumatoid arthritis
Glycogen storage disease type 1
Goodpasture syndrome
Henoch–Schönlein purpura
A urinary tract infection which has spread to the kidney(s)
Sjögren syndrome
Post-infectious glomerulonephritis
Living kidney donor
Polycystic kidney disease

Bence–Jones proteinuria

Amyloidosis
Pre-malignant plasma cell dyscrasias:
Monoclonal gammopathy of undetermined significance
Smoldering multiple myeloma
Malignant plasma cell dyscrasias
Multiple myeloma
Waldenström's macroglobulinemia
Other malignancies
Chronic lymphocytic leukemia
Rare cases of other Lymphoid leukemias
Rare cases of Lymphomas

Pathophysiology

Protein is the building block of all living organisms. When kidneys are functioning properly by filtering the blood, they distinguish the proteins from the wastes which were previously present together in the blood.

Albumin and immunoglobins

Albumin is a protein produced by the liver which makes up roughly 50%-60% of the total proteins in the blood while the other 40%-50% are proteins other than albumin, such as immunoglobins.

Diagnosis

{|class="wikitable" align="right"

!colspan=3| Protein dipstick grading

!rowspan=2| Designation !! colspan=2| Approx. amount

| Concentration || Daily

| Trace || 5–20 mg/dL ||

| 1+ || 30 mg/dL || Less than 0.5 g/day

| 2+ || 100 mg/dL || 0.5–1 g/day

| 3+ || 300 mg/dL || 1–2 g/day

| 4+ || More than 1000 mg/dL || More than 2 g/day

Conventionally, proteinuria is diagnosed by a simple dipstick test, although it is possible for the test to give a false negative reading, even with nephrotic range proteinuria if the urine is dilute. False negatives may also occur if the protein in the urine is composed mainly of globulins or Bence Jones proteins because the reagent on the test strips, bromophenol blue, is highly specific for albumin. Traditionally, dipstick protein tests would be quantified by measuring the total quantity of protein in a 24-hour urine collection test, and abnormal globulins by specific requests for protein electrophoresis.

More recently developed technology detects human serum albumin (HSA) through the use of liquid crystals (LCs). The presence of HSA molecules disrupts the LCs supported on the AHSA-decorated slides thereby producing bright optical signals which are easily distinguishable. Using this assay, concentrations of HSA as low as 15 μg/mL can be detected.

Alternatively, the concentration of protein in the urine may be compared to the creatinine level in a spot urine sample. This is termed the protein/creatinine ratio. The 2005 UK Chronic Kidney Disease guidelines state that protein/creatinine ratio is a better test than 24-hour urinary protein measurement. Proteinuria is defined as a protein/creatinine ratio greater than 45 mg/mmol (which is equivalent to albumin/creatinine ratio of greater than 30 mg/mmol or approximately 300 mg/g) with very high levels of proteinuria having a ratio greater than 100 mg/mmol.

Protein dipstick measurements should not be confused with the amount of protein detected on a test for microalbuminuria which denotes values for protein for urine in mg/day versus urine protein dipstick values which denote values for protein in mg/dL. That is, there is a basal level of proteinuria that can occur below 30 mg/day which is considered non-pathology. Values between 30 and 300 mg/day are termed microalbuminuria which is considered pathologic. Urine protein lab values for microalbumin of >30 mg/day correspond to a detection level within the "trace" to "1+" range of a urine dipstick protein assay. Therefore, positive indication of any protein detected on a urine dipstick assay obviates any need to perform a urine microalbumin test as the upper limit for microalbuminuria has already been exceeded.

Analysis

It is possible to analyze urine samples in determining albumin, hemoglobin and myoglobin with an optimized MEKC method.

Treatment

The most common cause is diabetic nephropathy; in this case, proper glycemic control may slow the progression. Medical management consists of angiotensin converting enzyme (ACE) inhibitors, which are typically first-line therapy for proteinuria. In patients whose proteinuria is not controlled with ACE inhibitors, the addition of an aldosterone antagonist (i.e., spironolactone) or angiotensin receptor blocker (ARB) may further reduce protein loss.

Atrasentan (Vanrafia) was approved for medical use in the United States in April 2025.