Proteinuria
Encyclopedia
Proteinuria means the presence of an
excess of serum
protein
s 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.
Proteinuria can also be caused by certain biological agents, such as bevacizumab
(Avastin) used in cancer treatment.
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 (human serum albumin) 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.
) 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
.
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.
excess of serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
in the urine (bilirubinuria
Bilirubinuria
In medicine, bilirubinuria is an abnormality where conjugated bilirubin is detected in the urine.The term "biliuria" is very similar, but more general. It refers to the presence of any bile pigment in the urine.-Causes:...
), retrograde ejaculation
Retrograde ejaculation
In the human male reproductive system, retrograde ejaculation occurs when semen, which would normally be ejaculated via the urethra, is redirected to the urinary bladder. Normally, the sphincter of the bladder contracts before ejaculation forcing the semen to exit via the urethra, the path of least...
, pneumaturia (air bubbles in the urine) due to a fistula
Fistula
In medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...
, or drugs such as pyridium.
Causes
There are three main mechanisms to cause proteinuria:- Due to disease in glomerulusGlomerulusA glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...
- Because of increased quantity of proteins in serumBlood serumIn blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
(overflow proteinuria) - Due to low reabsorption at proximal tubuleProximal tubuleThe proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.-Structure and appearance:...
(fanconiFanconi syndromeFalconi syndrome is a disease of the proximal renal tubules of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid...
)
Proteinuria can also be caused by certain biological agents, such as bevacizumab
Bevacizumab
Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....
(Avastin) used in cancer treatment.
Measurement
| Protein dipstick grading | ||
|---|---|---|
| Designation | | 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 2000 mg/dL | More than 2 g/day |
3.1 Conventional Measures
Proteinuria is often diagnosed by a simple dipstick
Dipstick
A dipstick is one of several measurement devices.Some dipsticks are dipped into a liquid to perform a chemical test or to provide a measure of quantity of the liquid....
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
Protein electrophoresis
Protein electrophoresis is a method for analysing the proteins in a fluid or an extract. The electrophoresis may be performed with a small volume of sample in a number of alternative ways with or without a supporting medium: SDS polyacrylamide gel electrophoresis Protein electrophoresis is a method...
. 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
Tamm-Horsfall protein
The Tamm-Horsfall glycoprotein also known as uromodulin is a glycoprotein that in humans is encoded by the UMOD gene. Up to 150 mg/dl of uromodulin may be excreted in the urine, making it the most abundant protein in normal urine.- Gene :...
.
3.2 Recent technologies
Other recent technologies used to detect HSA (human serum albumin) 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
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
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
Microalbuminuria
Microalbuminuria occurs when the kidney leaks small amounts of albumin into the urine, in other words, when there is an abnormally high permeability for albumin in the renal glomerulus.-Diagnosis:...
of greater than 30 mg/mmol or approximately 300 mg/g) with very high levels of nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
being for a PCR greater than 100 mg/mmol.
Associated conditions
Proteinuria may be a sign of renal (kidneyKidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
) 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
Hypoproteinemia
Hypoproteinemia is a condition where there is an abnormally low level of protein in the blood.One common cause is due to excess protein in the urine , which can be a medical sign of nephrotic syndrome....
can develop which results in
diminished oncotic pressure
Oncotic pressure
Oncotic pressure, or colloid osmotic pressure, is a form of osmotic pressure exerted by proteins in blood plasma that usually tends to pull water into the circulatory system.Throughout the body, dissolved compounds have an osmotic pressure...
. Symptoms of diminished oncotic pressure may include ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
, edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
and hydrothorax
Hydrothorax
A hydrothorax is a condition that results from serous fluid accumulating in the pleural cavity. This specific condition can be related to cirrhosis with ascites in which ascitic fluid leaks into the pleural cavity...
.
Conditions with proteinuria as a sign
Proteinuria may be a feature of the following conditions:- Nephrotic syndromes (i.e. intrinsic renal failure)
- Pre-eclampsiaPre-eclampsiaPre-eclampsia or preeclampsia is a medical condition in which hypertension arises in pregnancy in association with significant amounts of protein in the urine....
- EclampsiaEclampsiaEclampsia , an acute and life-threatening complication of pregnancy, is characterized by the appearance of tonic-clonic seizures, usually in a patient who had developed pre-eclampsia...
- Toxic lesions of kidneyKidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s - Collagen vascular diseases (e.g. systemic lupus erythematosusLupus erythematosusLupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
) - Dehydration
- GlomerularGlomerulusA glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...
diseases, such as membranous glomerulonephritisMembranous glomerulonephritisMembranous glomerulonephritis is a slowly progressive disease of the kidney affecting mostly patients between ages of 30 and 50 years, usually Caucasian.It is one of the more common forms of nephrotic syndrome.-Terminology:...
, focal segmental glomerulonephritisGlomerulonephritisGlomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
, minimal change disease (lipoid nephrosis) - Strenuous exercise
- Stress
- Benign orthostatic (postural) proteinuria
- Focal segmental glomerulosclerosisFocal segmental glomerulosclerosisFocal segmental glomerulosclerosis is a cause of nephrotic syndrome in children and adolescents, as well as an important cause of kidney failure in adults.It is also known as "focal glomerular sclerosis" or "focal nodular glomerulosclerosis"....
(FSGS) - IgA nephropathyIgA nephropathyIgA nephropathy is a form of glomerulonephritis...
(i.e. Berger's disease) - IgM nephropathy
- Membranoproliferative glomerulonephritisMembranoproliferative glomerulonephritisMembranoproliferative glomerulonephritis , also known as mesangiocapillary glomerulonephritis, is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane thickening, activating complement and damaging the glomeruli.MPGN accounts for approximately 4%...
- Membranous nephropathy
- Minimal change diseaseMinimal change diseaseMinimal Change Disease is a disease of the kidney that causes nephrotic syndrome and usually affects children .-Epidemiology:...
- SarcoidosisSarcoidosisSarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
- Alport's syndrome
- Diabetes mellitusDiabetes mellitusDiabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
(diabetic nephropathyDiabetic nephropathyDiabetic nephropathy , also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse...
) - Drugs (e.g. NSAIDs, nicotineNicotineNicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
, penicillaminePenicillaminePenicillamine is a pharmaceutical of the chelator class. It is sold under the trade names of Cuprimine and Depen. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic...
, gold and other heavy metals, ACE inhibitors, antibiotics, or opiates (especially heroin) - Fabry's diseaseFabry's diseaseFabry disease is a rare X-linked recessive lysosomal storage disease, which can cause a wide range of systemic symptoms...
- Infections (e.g. HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, syphilisSyphilisSyphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
, hepatitisHepatitisHepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
, poststreptococcal infection) - AminoaciduriaAminoaciduriaAminoaciduria is the presence of amino acids in the urine. Small amounts of amino acids are also present in normal urine. Increased total urine amino acids may result from metabolic disorders, chronic liver disease or renal disorders. Aminoacidurias can be divided into primary and secondary...
- Fanconi syndromeFanconi syndromeFalconi syndrome is a disease of the proximal renal tubules of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid...
- Hypertensive nephrosclerosis
- Interstitial nephritisInterstitial nephritisInterstitial nephritis is a form of nephritis affecting the interstitium of the kidneys surrounding the tubules...
- Sickle cell disease
- HemoglobinuriaHemoglobinuriaIn medicine, hemoglobinuria or haemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is often associated with hemolytic anemia, in which red blood cells are destroyed, thereby increasing levels of free...
- Multiple myelomaMultiple myelomaMultiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
- MyoglobinuriaMyoglobinuriaMyoglobinuria is the presence of myoglobin in the urine, usually associated with rhabdomyolysis or muscle destruction. Myoglobin is present in muscle cells as a reserve of oxygen.-Causes:...
- 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 feverFamilial Mediterranean feverFamilial Mediterranean fever is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in MEFV, a gene which encodes a 781–amino acid protein denoted pyrin....
- HELLP SyndromeHELLP syndromeHELLP syndrome is a life-threatening obstetric complication usually considered to be a variant of pre-eclampsia. Both conditions usually occur during the later stages of pregnancy, or sometimes after childbirth.HELLP is an abbreviation of the main findings:...
- Systemic lupus erythematosusSystemic lupus erythematosusSystemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
- Wegener's granulomatosisWegener's granulomatosisWegener's granulomatosis , more recently granulomatosis with polyangiitis , is an incurable form of vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end-organ damage, it is life-threatening and requires long-term immunosuppression...
- Rheumatoid arthritis
- Glycogen storage diseaseGlycogen storage diseaseGlycogen storage disease is the result of defects in the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types. GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism involved in these processes...
type 1 - Goodpasture's syndromeGoodpasture's syndromeGoodpasture’s syndrome is a rare disease characterized by glomerulonephritis and hemorrhaging of the lungs...
- 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 leukemiaChronic lymphocytic leukemiaB-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
- AmyloidosisAmyloidosisIn medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
- Malignancies (e.g., lymphoma, other cancers)
- Multiple myelomaMultiple myelomaMultiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
Treatment
Treating proteinuria mainly needs proper diagnosis of the cause.The most common cause is diabetic nephropathy
Diabetic nephropathy
Diabetic nephropathy , also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse...
; 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
Spironolactone
Spironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
) 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.
See also
- AlbuminuriaAlbuminuriaAlbuminuria is a pathological condition wherein albumin is present in the urine. It is a type of proteinuria.Measurement=The amount of protein being lost in the urine can be quantified by collecting the urine for 24 hours, measuring a sample of the pooled urine, and extrapolating to the volume...
- MicroalbuminuriaMicroalbuminuriaMicroalbuminuria occurs when the kidney leaks small amounts of albumin into the urine, in other words, when there is an abnormally high permeability for albumin in the renal glomerulus.-Diagnosis:...
- List of terms associated with diabetes
- Protein toxicityProtein toxicityProtein toxicity with proteinuria can result in those with preexisting kidney disease, or those who have lost kidney function due to age.-Definition:...
- Major urinary proteinsMajor urinary proteinsMajor urinary proteins , also known as α2u-globulins, are a subfamily of proteins found in abundance in the urine and other secretions of many animals. Mups provide a small range of identifying information about the donor animal, when detected by the vomeronasal organ of the receiving animal. They...