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Isolated proteinuria

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Title: Isolated proteinuria  
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Isolated proteinuria

Proteinuria
ICD-10 9 DiseasesDB eMedicine MeSH D011507

Proteinuria (/prtˈnʊəriə/ or /prtˈnjʊəriə/; from protein and urine) means the presence of an excess of serum proteins in the urine. The excess protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine (bilirubinuria),[1] retrograde ejaculation,[2] pneumaturia (air bubbles in the urine) due to a fistula,[3] or drugs such as pyridium.[1]

Up to 150 mg a day of protein may be excreted by a normal person, primarily the Tamm-Horsfall protein.

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 syndrome)

Proteinuria can also be caused by certain biological agents, such as bevacizumab (Avastin) used in cancer treatment, or by excessive fluid intake (drinking in excess of 4 litres of water per day).[4][5]

Measurement

Protein dipstick grading
Designation Approx. amount
Concentration[6] Daily[7]
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 2000 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,[8] 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.[9][10] 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.[1][11] Trace results may be produced in response to excretion of Tamm-Horsfall mucoprotein.

Recent technologies used to detect human serum albumin (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.=using this assay can be as low as 15 ug/mL.[12]

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 proteinuria being for a PCR greater than 100 mg/mmol.[13]

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 30–300 mg/day are termed microalbuminuria which is considered pathologic.[14] 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.[15]

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:[10]

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

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)[19] or angiotensin receptor blocker (ARB)[20] 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.

See also

References

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