Proteinuria

Proteinuria ( or ; from protein and urine) means the presence of an excess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine (bilirubinuria), retrograde ejaculation, pneumaturia (air bubbles in the urine) due to a fistula, or drugs such as pyridium.

Causes
There are three main mechanisms to cause proteinuria:
 * Due to disease in glomerulus
 * Because of increased quantity of proteins in serum (overflow proteinuria)
 * Due to low reabsorption at proximal tubule (fanconi)

Proteinuria can also be caused by certain biological agents, such as bevacizumab (Avastin) used in cancer treatment.

Measurement
3.1 Conventional Measures Proteinuria is often diagnosed by a simple dipstick test, although it is possible for the test to give a false negative 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, bromphenol 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. However, some studies show that urine dipstick is not accurate and could sometimes give false readings. Trace results may be produced in response to excretion of Tamm-Horsfall mucoprotein.

3.2 Recent technologies Other recent technologies used to detect HSA is 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. Incorporating a dilution protocol, the quantification of the amount of HSA present in the urine sample was successfully achieved simply by counting the number of bright spots. HSA concentrations detected using this assay can be as low as 15 ug/mL.

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 (PCR). The 2005 UK Chronic Kidney Disease guidelines states PCR 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 nephrotic syndrome being for a PCR greater than 100 mg/mmol.

Associated conditions
Proteinuria may be a sign of renal (kidney) damage. Since serum proteins are readily reabsorbed from urine, the presence of excess protein indicates either an insufficiency of absorption or impaired filtration. Diabetics may suffer from damaged nephrons and develop proteinuria. The most common cause of proteinuria is diabetes, and in any person with proteinuria and diabetes, the etiology of the underlying proteinuria should be separated into two categories: diabetic proteinuria versus the field.

With severe proteinuria, general hypoproteinemia can develop which results in diminished oncotic pressure. Symptoms of diminished oncotic pressure may include ascites, edema and hydrothorax.

Conditions with proteinuria as a sign
Proteinuria may be a feature of the following conditions:
 * Nephrotic syndromes (i.e. intrinsic renal failure)
 * Pre-eclampsia
 * Eclampsia
 * Toxic lesions of kidneys
 * Collagen vascular diseases (e.g. systemic lupus erythematosus)
 * Dehydration
 * Glomerular diseases, such as membranous glomerulonephritis, focal segmental glomerulonephritis, minimal change disease (lipoid nephrosis)
 * Strenuous exercise
 * Stress
 * Benign orthostatic (postural) proteinuria
 * Focal segmental glomerulosclerosis (FSGS)
 * IgA nephropathy (i.e. Berger's disease)
 * IgM nephropathy
 * Membranoproliferative glomerulonephritis
 * Membranous nephropathy
 * Minimal change disease
 * Sarcoidosis
 * Alport's syndrome
 * Diabetes mellitus (diabetic nephropathy)
 * Drugs (e.g. NSAIDs, nicotine, penicillamine, gold and other heavy metals, ACE inhibitors, antibiotics, or opiates (especially heroin)
 * Fabry's disease
 * Infections (e.g. HIV, syphilis, hepatitis, poststreptococcal infection)
 * Aminoaciduria
 * Fanconi syndrome
 * Hypertensive nephrosclerosis
 * Interstitial nephritis
 * Sickle cell disease
 * Hemoglobinuria
 * Multiple myeloma
 * Myoglobinuria
 * Organ rejection: Kidney transplant patients may have gamma-globulins in their urine if the kidneys start to reject.
 * Ebola hemorrhagic fever
 * Nail patella syndrome
 * Familial Mediterranean fever
 * HELLP Syndrome
 * Systemic lupus erythematosus
 * Wegener's granulomatosis
 * Rheumatoid arthritis
 * Glycogen storage disease type 1
 * Goodpasture's syndrome
 * Henoch Schonlein Purpura
 * A urinary tract infection which has spread to the kidney(s)

Conditions with proteinuria consisting mainly of Bence-Jones proteins as a sign

 * Waldenstrom's macroglobulinemia
 * Chronic lymphocytic leukemia
 * Amyloidosis
 * Malignancies (e.g., lymphoma, other cancers)
 * Multiple myeloma

Treatment
Treating proteinuria mainly needs proper diagnosis of the cause. 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. Caution must be used if these agents are added to ACE inhibitor therapy due to the risk of hyperkalemia. Proteinuria secondary to autoimmune disease should be treated with steroids or steroid-sparing agent plus the use of ACE inhibitors.