Proteinuria

Proteinuria
Various test tubes of urine
Pronunciation	/ˌproʊtiːˈnjʊəriə/
Specialty	Nephrology
Complications	Protein toxicity

Proteinuria is the presence of excess

Proteinuria often causes no symptoms and it may only be discovered incidentally.[1]

Foamy urine is considered a cardinal sign of proteinuria, but only a third of people with foamy urine have proteinuria as the underlying cause.

There are three main mechanisms to cause proteinuria:[5]

• 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 4 litres of water per day) is another cause.^[6][7]

Proteinuria may be a sign of renal (

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

Proteinuria may be a feature of the following conditions:^[8]

• Nephrotic syndromes (i.e. intrinsic kidney failure
  )
• Pre-eclampsia
• Eclampsia
• Toxic lesions of kidneys
• Amyloidosis
• Collagen vascular diseases (e.g.
  systemic lupus erythematosus
  )
• Dehydration
• 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 syndrome
• Diabetes mellitus (diabetic nephropathy
  )
• Drugs (e.g.
  opiates (especially heroin)^[9]
• Fabry disease
• Infections (e.g. HIV, syphilis, hepatitis, poststreptococcal infection, urinary schistosomiasis)
• Aminoaciduria
• Wilson disease
• Hypertensive nephrosclerosis
• Interstitial nephritis
• Sickle cell disease
• Hemoglobinuria
• Multiple myeloma
• Myoglobinuria
• Organ rejection:^[10]
• Ebola virus disease
• Nail–patella syndrome
• Familial Mediterranean fever
• HELLP syndrome
• Systemic lupus erythematosus
• Granulomatosis with polyangiitis
• Rheumatoid arthritis
• Glycogen storage disease type 1^[11]
• Goodpasture syndrome
• Henoch–Schönlein purpura
• A urinary tract infection which has spread to the kidney(s)
• Sjögren syndrome
• Post-infectious glomerulonephritis
• Living kidney donor^[12]
• Polycystic kidney disease^[13]

This list is incomplete; you can help by adding missing items. (December 2008)

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.^[14] When kidneys are functioning properly by filtering the blood, they distinguish the proteins from the wastes which were previously present together in the blood.^[14] Thereafter, kidneys retain or reabsorb the filtered proteins and return them to the circulating blood while removing wastes by excreting them in the urine.^[14] Whenever the kidney is compromised, their ability to filter the blood by differentiating protein from the waste, or retaining the filtered protein then returning which back to the body, is damaged.^[14] As a result, there is a significant amount of protein to be discharged along with waste in the urine that makes the concentration of proteins in urine high enough to be detected by medical machine.^[14]

Medical testing equipment has improved over time, and as a result tests are better able to detect smaller quantities of protein.^[14] Protein in urine is considered normal as long as the value remains within the normal reference range.^[14] Variation exists between healthy patients, and it is generally considered harmless for the kidney to fail to retain a few proteins in the blood, letting those protein discharge from the body through urine.^[14]

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.^[15][14] This is why the concentration of albumin in the urine is one of the single sensitive indicators of kidney disease, particularly for those with diabetes or hypertension, compared to routine proteinuria examination.^[14]

As the loss of proteins from the body progresses, the suffering will gradually become symptomatic.^[14]

The exception applies to the scenario when there's an overproduction of proteins in the body, in which the kidney is not to blame.^[14]

Diagnosis

Conventionally, proteinuria is diagnosed by a simple

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.^[22]

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.^[23]

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.^[24] 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.^[25]

Analysis

It is possible to analyze urine samples in determining albumin, hemoglobin and myoglobin with an optimized MEKC method.^[26]

Treatment

Treating proteinuria mainly needs proper diagnosis of the cause. The most common cause is

See also

• Albuminuria
• Microalbuminuria
• List of terms associated with diabetes
• Protein toxicity
• Major urinary proteins
• UPCR

References