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]; Sapan Patel M.B.B.S; Ogheneochuko Ajari, MB.BS, MS [3]; Mahmoud Sakr, M.D. [4]

Synonyms and Keywords: Elevated urinary protein levels; Elevated urine protein

To view a comprehensive algorithm of common findings of urine composition and urine output, click here

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

Common Causes

Causes by Organ System

Cardiovascular Amyloidosis, benign orthostatic proteinuria, constrictive pericarditis, dehydration, eclampsia, hypertension, Nutcracker syndrome, preeclampsia, renal artery stenosis, renal vein thrombosis, shock , subacute bacterial endocarditis, tricuspid insufficiency
Chemical/Poisoning Nitrosourea compounds, mercury, cadmium, trichloroethlene, bromobenzene , chloroform, aristolochic acids , paraquat, diquat, ethylene glycol
Dental No underlying causes
Dermatologic Scleroderma
Drug Side Effect Acetaminophen and Oxycodone, Aflibercept, anticonvulsants, Artemether and lumefantrin, bevacizumab, captopril, carmustine, caspofungin, cisplatin, deferasirox, diflunisal, febuxostat, gemcitabine, gold, heavy metal ingestion, heroin, Interferon gamma, Lenvatinib, Lincomycin Hydrochloride, lomustine, micafungin, mithramycin, NSAIDS, Olsalazine, Oxaprozin, pazopanib, penicillamine, pramipexole, rifaximin, Sodium aurothiomalate, Sorafenib, Streptozocin, sulfasalazine, sulindac, Telavancin hydrochloride, [Thalidomide]], Tolmetin , Ziv-aflibercept
Ear Nose Throat No underlying causes
Endocrine Diabetes mellitus, hypothyroidism
Environmental Allergens, irradiation
Gastroenterologic Cirrhosis of liver, Wilson's disease, hemochromatosis
Genetic Alport syndrome, Alström syndrome, aminoaciduria, amyloidosis, Balkan nephropathy, connatal tubulopathies, cystinosis, Dent disease, diabetes mellitus, Fabry's disease, familial mediterranean fever, galactosemia, glycogen storage disease type I, hepatorenal tyrosinemia, hereditary fructose intolerance, idiopathic multicentric osteolysis, Imerslund-Grasbeck syndrome, Lecithin cholesterol acyltransferase deficiency, Nail-patella syndrome, polycystic kidney disease , recurrent hereditary polyserositis, Wilson's disease, X-linked hypophosphatemia
Hematologic No underlying causes
Iatrogenic No underlying causes
Infectious Disease Epstein-barr virus, helminthic, hepatitis B, HIV, infectious mononucleosis, Legionella pneumophila, leprosy, malaria, poststreptococcal glomerulonephritis, Prostitis, acute Pyelonephritis, Subacute bacterial endocarditis, toxoplasmosis, urinary tract infection, viral illness, yellow fever, genitourinary tuberculosis
Musculoskeletal/Orthopedic rhabdomyolysis
Neurologic No underlying causes
Nutritional/Metabolic extreme obesity
Obstetric/Gynecologic Eclampsia, preeclampsia
Oncologic Renal cell carcinoma, multiple myeloma
Ophthalmologic No underlying causes
Overdose/Toxicity No underlying causes
Psychiatric stress
Pulmonary No underlying causes
Renal/Electrolyte Amyloidosis, Bence-jones proteinuria, crescentic glomerulonephritis, dehydration, Fanconi syndrome, fibrillary glomerulopathies, focal segmental glomerulosclerosis , hyperoxaluria, hypertension-related kidney failure, hyperuricemia, hypokalemic nephropathy, interstitial nephritis, medullary cystic kidney disease, myoglobinuria, nephritic syndrome, nephritis of pregnancy, nephrotic syndrome), Papillary necrosis, autosomal dominant polycystic kidney disease ), Poststreptococcal glomerulonephritis, Proliferative glomerulonephritis, Proximal renal tubular acidosis, acute Pyelonephritis, renal artery stenosis, renal metastases, renal neoplasm, renal tubular acidosis, renal vein thrombosis, rhabdomyolysis, toxic nephropathy, unilateral kidney, Urinary tract infection, X-linked hypophosphataemia
Rheumatology/Immunology/Allergy Allergens, arteriolar nephrosclerosis, autoimmune conditions, Bence-jones proteinuria, Collagen vascular diseases, crescentic glomerulonephritis, Fanconi syndrome, fibrillary glomerulopathies, focal segmental glomerulosclerosis ), Henoch-schonlein syndrome, hepatitis b, IgA nephropathy (i.e., Berger's disease), IgM nephropathy, increased formation of polyclonal free light chains, interstitial nephritis, mixed cryoglobulinemia, multiple myeloma, Organ rejection- kidney transplant patients], Polyarteritis nodosa, recurrent hereditary polyserositis, rheumatoid disease, sarcoidosis, systemic lupus erythematosis, systemic sclerosis, Wegener's granulomatosis
Sexual No underlying causes
Trauma musculoskeletal trauma
Urologic Retrograde ejaculation
Miscellaneous No underlying causes

Causes in Alphabetical Order

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. [7][8] 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.[9][10]

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.[11]

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)[12] or angiotensin receptor blocker (ARB)[13] 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

  1. The American Heritage Stedman's Medical Dictionary. "KMLE Medical Dictionary Definition of proteinuria".  Retrieved 2007-01-20
  2. http://www.pathguy.com/lectures/urine.htm Retrieved 2007-01-20
  3. http://www.medhelp.org/forums/urology/archive/195.html Retrieved 2007-01-20
  4. Pneumaturia at GPnotebook Retrieved 2007-01-20
  5. http://www.pathguy.com/lectures/urine.htm Retrieved 2007-01-20
  6. 6.0 6.1 Van Vleet TR, Schnellmann RG (2003). "Toxic nephropathy: environmental chemicals.". Semin Nephrol. 23 (5): 500–8. PMID 13680539. 
  7. http://medlib.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.html Retrieved 2007-01-20
  8. Simerville JA, Maxted WC, Pahira JJ (2005). "Urinalysis: a comprehensive review". American family physician. 71 (6): 1153–62. PMID 15791892. 
  9. http://www.pathguy.com/lectures/urine.htm Retrieved 2007-01-20
  10. http://www.answers.com/topic/protein-electrophoresis Retrieved 2007-01-20
  11. "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
  12. 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. PMC 2794224Freely accessible. PMID 19926893. doi:10.1681/ASN.2009070737. 
  13. 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. PMC 2663827Freely accessible. PMID 19211712. doi:10.1681/ASN.2008040416. 

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