Proteinuria

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Synonyms and keywords: Urinary protein levels raised; urine protein raised

Overview

Proteinuria (from protein and urine) means the presence of an excess of serum proteins in the urine.^[1] 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),^[2] retrograde ejaculation,^[3] pneumaturia (air bubbles in the urine) due to a fistula,^[4] or drugs such as pyridium.^[5]

Causes

Proteinuria may be a feature of the following conditions:^[6]

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
Drugs (e.g., NSAIDs, nicotine, penicillamine, gold, ACE inhibitors, antibiotics, opiates especially heroin.^[7]
Fabry's disease
Infections (e.g., HIV, syphilis, hepatitis,post-streptococcal infection)
Aminoaciduria
Fanconi syndrome
Heavy metal ingestion
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.^[8]
Ebola hemorrhagic fever
Nail Patella syndrome
Familial Mediterranean fever

Causes of Proteinuria by Type

Bence-Jones proteinuria

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

Glomerular Proteinuria

Allergins
Glomerulonephritis

Collagen Vascular Disease

Drugs
Hereditary

Infections

Miscellaneous

Tubular Proteinuria

Connatal tulbulopathies
Hypokalemic nephropathy
Interstitial nephropathy
Renal Vein Thrombosis
Renal tubular acidosis
Toxic nephropathy

Prerenal and Overflow Proteinuria

Bence-Jones Proteinuria
Hemoglobinura
Increased formation of polyclonal free light chains
Myoglobinuria

Renal Parenchymal and Post Renal Proteinuria

Hemmorhage in the urinary tract
Local infections
Nephrolithiasis
Prostitis
Tamm-Horsfall protein

Miscellaneous Causes of Proteinuria

Arteriolar nephrosclerosis
Chronic Pyelonephritis
Constrictive Pericarditis
Genitourinary Tuberculosis
High Fever
Malignant Hypertension
Massive Obesity
Orthostatic proteinuria
Preeclampsia
Renal Neoplasm
Renal Vein Thrombosis
Tricuspid insufficiency
Unilateral kidney

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.

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

Diagnosis

Laboratory Findings

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 globulins or Bence-Jones Proteins because the reagent on the test strips, Bromphenol blue, is highly specific for albumin. ^[9]^[6] 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.^[10]^[11]

Alternatively the concentration of protein in the urine may be compared to the creatinine level in a spot urine sample. This is termed Protein/Creatinine Ratio (PCR). The 2005 UK Chronic Kidney Disease guidelines states that PCR is a better test than 24 hour urinary protein measurement. Proteinuria is defined as a Protein:creatinine ratio >45 mg/mmol (which is equivalent to Albumin:creatinine ratio of >30 mg/mmol) with very high levels of nephrotic syndrome being for PCR > 100 mg/mmol.^[12]

Reference Range
Physiologic protien elimination	<150mg protien/24 hours
Proteinuria	>150mg protein/24 hours
Microalbuminuria	<30mg albumin/24 hours

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)^[13] or angiotensin receptor blocker (ARB)^[14] 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.

Related Chapters

References

↑ The American Heritage Stedman's Medical Dictionary. "KMLE Medical Dictionary Definition of proteinuria". Retrieved 2007-01-20
↑ http://www.pathguy.com/lectures/urine.htm Retrieved 2007-01-20
↑ http://www.medhelp.org/forums/urology/archive/195.html Retrieved 2007-01-20
↑ Template:GPnotebook Retrieved 2007-01-20
↑ http://www.pathguy.com/lectures/urine.htm Retrieved 2007-01-20
↑ ^6.0 ^6.1 Simerville JA, Maxted WC, Pahira JJ (2005). "Urinalysis: a comprehensive review". American family physician. 71 (6): 1153–62. PMID 15791892.
↑ Dettmeyer RB, Preuss J, Wollersen H, Madea B (2005). "Heroin-associated nephropathy". Expert opinion on drug safety. 4 (1): 19–28. PMID 15709895.
↑ Hermann G, Zühlke V, Faul P (1970). "Gamma globulin fragments in urine of kidney transplant patients in relation to rejection crisis". European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes. 2 (1): 55–63. PMID 4131420.
↑ http://medlib.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.html Retrieved 2007-01-20
↑ http://www.pathguy.com/lectures/urine.htm Retrieved 2007-01-20
↑ http://www.answers.com/topic/protein-electrophoresis Retrieved 2007-01-20
↑ "Identification, management and referral of adults with chronic kidney disease: concise guidelines" (PDF). UK Renal Association. 27/9/05. Check date values in: |date= (help) - see Guideline 4 Confirmation of proteinuria, on page 9
↑ Mehdi UF, Adams-Huet B, Raskin P; et al. (2009). "Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximum angiotensin-converting enzyme inhibition in diabetic nephropathy". J Am Soc Nephrol. 20 (12): 2641–50. doi:10.1681/ASN.2009070737. PMC 2794224. PMID 19926893.
↑ Burgess E, Muirhead N, Rene de Cotret P; et al. (2009). "Supramaximal dose of candesartan in proteinuric renal disease". J Am Soc Nephrol. 20 (4): 893–900. doi:10.1681/ASN.2008040416. PMC 2663827. PMID 19211712.

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[1] The American Heritage Stedman's Medical Dictionary. "KMLE Medical Dictionary Definition of proteinuria". Retrieved 2007-01-20

[2] ttp://www.pathguy.com/lectures/urine.htm Retrieved 2007-01-20

[3] ttp://www.medhelp.org/forums/urology/archive/195.html Retrieved 2007-01-20

[4] Template:GPnotebook Retrieved 2007-01-20

[5] ttp://www.pathguy.com/lectures/urine.htm Retrieved 2007-01-20

[pmid15791892-6] 6.0 ^6.1 Simerville JA, Maxted WC, Pahira JJ (2005). "Urinalysis: a comprehensive review". American family physician. 71 (6): 1153–62. PMID 15791892.

[pmid15709895-7] Dettmeyer RB, Preuss J, Wollersen H, Madea B (2005). "Heroin-associated nephropathy". Expert opinion on drug safety. 4 (1): 19–28. PMID 15709895.

[pmid4131420-8] Hermann G, Zühlke V, Faul P (1970). "Gamma globulin fragments in urine of kidney transplant patients in relation to rejection crisis". European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes. 2 (1): 55–63. PMID 4131420.

[9] ttp://medlib.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.html Retrieved 2007-01-20

[10] ttp://www.pathguy.com/lectures/urine.htm Retrieved 2007-01-20

[11] ttp://www.answers.com/topic/protein-electrophoresis Retrieved 2007-01-20

[12] "Identification, management and referral of adults with chronic kidney disease: concise guidelines" (PDF). UK Renal Association. 27/9/05. Check date values in: |date= (help) - see Guideline 4 Confirmation of proteinuria, on page 9

[Mehdi-13] Mehdi UF, Adams-Huet B, Raskin P; et al. (2009). "Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximum angiotensin-converting enzyme inhibition in diabetic nephropathy". J Am Soc Nephrol. 20 (12): 2641–50. doi:10.1681/ASN.2009070737. PMC 2794224. PMID 19926893.

[Burgess-14] Burgess E, Muirhead N, Rene de Cotret P; et al. (2009). "Supramaximal dose of candesartan in proteinuric renal disease". J Am Soc Nephrol. 20 (4): 893–900. doi:10.1681/ASN.2008040416. PMC 2663827. PMID 19211712.

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