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Urine and Urinalysis
All samples should be midstream and collected in a clean sterile container. Suprapubic aspiration or fresh catheter samples are ideal, but not always practical.
Physical examination
Colour
The colour of the urine can vary greatly. Normal urine varies from colourless to dark yellow. Various factors can affect urine colour.1
Common Causes of Urine Discolouration
Colour Pathological causes Food and drug causes
Brown Bile pigments, myoglobin, fava beans Levodopa, metronidazole, nitrofurantoin, some antimalarial agents
Brownish-black Bile pigments, melanin, methaemoglobin Cascara, levodopa, methyldopa, senna
Green or blue Pseudomonal UTI, biliverdin Amitriptyline, indigo carmine, IV cimetidine, IV promethazine, methylene blue, triamterene
Orange Bile pigments Phenothiazines, phenazopyridine
Red Haematuria, haemoglobinuria, myoglobinuria, porphyria Beets, blackberries, rhubarb, Phenolphthalein, rifampicin
Yellow Concentrated urine (orange to gold in dehydration) Carrots
Cascara
Turbidity
Cloudy urine may be due to excess phosphate crystals precipitating in alkaline urine, which is of no significance. It can however also be seen in pyuria secondary to infection,2 chyluria (usually secondary to filariasis),3 hyperuricosuria secondary to a diet high in purine-rich foods,4 lipiduria5 and hyperoxaluria.6
Odour1
The normal odour is described as urinoid. In concentrated specimens this can be strong but does not imply infection which has a more pungent smell. Alkaline fermentation causes an ammoniacal smell, and patients with diabetic ketoacidosis produce a urine that may have a sweet or fruity odour. Other causes of abnormal odours are cystine decomposition (a sulphuric smell), gastrointestinal-bladder fistulae (a faecal smell), medications (e.g.vitamin B6), and diet (e.g. asparagus).
Dipstick analysis
Immerse the dipstick completely in fresh urine and withdraw immediately, drawing the edge along rim of container to remove excess. Hold the dipstick horizontally before reading.
Specific Gravity SG <1.008 is dilute and >1.020 is concentrated.
Increased specific gravity is seen in conditions causing dehydration, glycosuria, renal artery stenosis, heart failure (secondary to decreased blood flow to the kidneys), inappropriate antidiuretic hormone secretion and proteinuria.7,8 Some dipsticks give falsely high readings in the presence of dextran solutions and IV radiopaque dyes,1 but this varies, so check the manufacturer's leaflet.1 The usefulness of specific gravity in identifying dehydration in infants has been brought into question.9
Decreased specific gravity is seen in excessive fluid intake, renal failure, pyelonephritis, and central and nephrogenic diabetes insipidus.10 False low readings are associated with alkaline urine (e.g. a high-citrate diet).1
pH
The range is 4.5 to 8, but urine is commonly acidic (i.e. 5.5-6.5) due to metabolic activity.
Acidic urine (low pH) may be caused by diet (e.g. acidic fruits such as cranberries).10 Urine pH generally reflects the blood pH but in renal tubular acidosis (RTA) this is not the case. In type 1 RTA (distal) the urine is acidic but the blood alkaline. In type 2 (proximal) the urine is initially alkaline but becomes more acidic as the disease progresses.11 Acidic urine may be associated with uric acid calculi.12
Alkaline urine (high pH) is seen in the initial stages of type 2 RTA and also with infection with urease-splitting organisms. Alkaline urine may be associated with the formation of stag-horn calculi.13
Haematuria
Dipstick testing for haematuria is based on the peroxidase activity of erythrocytes. However, haemoglobin and myoglobin will also catalyse this reaction. False positives are also seen in dehydration and menstruation.
False negatives are seen in patients taking captopril and vitamin C, proteinuria, elevated specific gravity, pH less than 5.1 and bacteriuria.1,14
Dipstick testing for haematuria is therefore at best a screening tool which needs the support of microscopy to make a definitive diagnosis.15
The causes of haematuria can be divided into those occurring at the glomerular level, renal (i.e. non-glomerular) and urological causes. Glomerular haematuria is typically associated with erythrocyte cases, dysmorphic red blood cells and significant proteinuria, although 20% of patients present with haematuria alone.1,16 Renal haematuria is also associated with significant proteinuria, but there are no associated dysmorphic RBCs or erythrocyte casts.1 Urologic haematuria is distinguished from other aetiologies by the absence of proteinuria, dysmorphic RBCs, and erythrocyte casts.1 Exercise-induced haematuria is a benign, relatively common condition often is associated with long-distance running. Results of repeat urinalysis after 48 to 72 hours should be negative.17
Causes of Haematuria1,18
Glomerular Causes
Familial causes Fabry's disease Hereditary nephritis
(Alport's syndrome)
Primary glomerulonephritis Focal segmental glomerulonephritis IgA nephropathy (Berger's disease)
Nail-patella syndrome Thin basement-membrane disease Goodpasture's disease
Henoch-Schönlein purpura Mesangioproliferative glomerulonephritis Postinfectious glomerulonephritis
Rapidly progressive glomerulonephritis Secondary glomerulonephritis Haemolytic-uremic syndrome
Systemic lupus nephritis Thrombotic thrombocytopenic purpura Vasculitis
Renal Causes
Arteriovenous malformation Hypercalciuria Hyperuricosuria
Loin pain-haematuria syndrome Malignant hypertension Medullary sponge kidney
Metabolic Causes Papillary necrosis Polycystic kidney disease
Renal artery embolism Renal vein thrombosis Sickle cell disease or trait
Proteinuria1
Normal urinary proteins include serum globulins, albumin, and proteins secreted by the nephron. Proteinuria is defined as albumin:creatinine ratio >30 mg/mmol or albumin concentration >200 mg/L. The loss of up to 150 mg of protein per day is normal. This may be expressed as less than 4 mg per hour per square metre of body surface area.19Clinical proteinuria is indicated at greater that 0.5g or protein per day (greater or equal to 0.3g/L on a test strip).
Most dipstick tests will pick up albumin but may not detect low concentrations of Bence-Jones protein or gamma-globulins. Bence-Jones protein can be detected by a specific antibody test on a mid-stream sample, whilst urine gamma-globulins can be detected by urine electrophoresis.
Proteinuria may be transient or persistent. Transient proteinuria is usually due to temporary changes in glomerular haemodynamics, and follows a benign course. Orthostatic proteinuria is a subset of this category, in which the phenomenon is seen after prolonged standing.20 It is confirmed by obtaining a negative result after eight hours of lying flat.
The causes of persistent proteinuria may be divided into glomerular, tubular and overflow. The commonest is glomerular proteinuria, in which albumin is the primary urine protein. Tubular protein is caused by malfunctioning tubule cells which are unable to reabsorb normally filtered protein. Low-molecular weight proteins predominate in this condition. Overflow proteinuria is caused by low-molecular weight proteins overwhelming the ability of the tubules to reabsorb filtered proteins.1
Persistent significant proteinuria detected by dipstick requires further assessment with 24-hour urinary protein excretion, urinary protein-creatinine ratio, microscopic examination of the urinary sediment, urinary protein electrophoresis, and assessment of renal function.21
Causes of Proteinuria1
Transient proteinuria
Congestive heart failure Dehydration Emotional stress
Exercise Fever Orthostatic (postural) proteinuria
Seizures Persistent proteinuria Primary glomerular causes
Focal segmental glomerulonephritis IgA nephropathy (i.e. Berger's disease) IgM nephropathy
Membranoproliferative glomerulonephritis Membranous nephropathy Minimal change disease
Secondary glomerular causes
Alport's syndrome Amyloidosis Collagen vascular diseases
(e.g. systemic lupus erythematosus)
Diabetes mellitus Drugs (e.g. NSAIDs, penicillamine [Cuprimine],
gold, ACE inhibitors) Fabry's disease
Sickle cell disease Malignancies (e.g. lymphoma, solid tumors) Sarcoidosis
Infections (e.g. HIV, syphilis, hepatitis,post-streptococcal infection)
Tubular causes
Aminoaciduria Drugs (e.g. NSAIDs, antibiotics) Fanconi syndrome
Heavy metal ingestion Hypertensive nephrosclerosis Interstitial nephritis
Overflow causes
Haemoglobinuria Multiple myeloma Myoglobinuria
Glycosuria
Glucose is normally filtered by the glomerulus, but small amounts (1.67mmol/L or 30 mg/dL) do reach the urine.20 These amounts are usually below the sensitivity level of dipsticks but may occasionally produce a positive result. Causes of glycosuria include diabetes mellitus, Cushing's syndrome, liver and pancreatic disease, and Fanconi's syndrome.1
The test is specific for glucose but false positive results may be seen when high levels of ketones are present22 and in patients taking levodopa.23
False negatives are seen where specific gravity is elevated,22 in uricosuria24 and in patients taking ascorbic acid.25
Ketones
Ketones are not normally found in urine.1,20 The reagent on a dipstick detects acetic acid, but does not react to acetone or beta-hydroxybutyric acid. A positive test is associated with uncontrolled diabetes,26 pregnancy without diabetes,27 carbohydrate-free diets28 and starvation.29
False trace results may be seen in highly-pigmented urine and in patients taking levodopa.1
Delay in testing a sample may result in a false negative result.1
Nitrites
This test relies on the breakdown of urinary nitrates to nitrites, which are not found in normal urine. Many Gram-negative and some Gram-positive bacteria are capable of producing this reaction and a positive test suggests their presence in significant numbers (i.e. more than 10,000 per ml). A negative result does not rule out a urinary tract infection.1,30
The reagent is highly sensitive to air exposure, which may cause a false positive response.31
False negative results may be seen where bladder incubation time is shortened (less than 4 hours), in the absence of dietary nitrate, in the presence of nitrate-reductase negative organisms (e.g. some Mycobacteria strains,32) when urine specific gravity is elevated,1 where pH is less than 6.0,1 and in the presence of urobilinogen and urinary vitamin C.33
Leucocytes
This relies on the reaction of leukocyte esterase produced by neutrophils and a positive result suggests pyuria associated with urinary tract infection.1 Isolated trace results may be of questionable significance, but repeated ones should not be ignored.34
False positive results may be caused by contamination with vaginal discharge.1
Elevated urine glucose or oxalic acid concentrations may reduce sensitivity, and this may also be seen in patients taking tetracycline or cefalexin.1
Bilirubin and urobilinogen
Unconjugated bilirubin is water insoluble and not normally present in the urine. The presence of conjugated bilirubin indicates further evaluation for liver dysfunction and biliary obstruction. A small amount of urobilinogen is normally found in urine, but significant amounts suggest that further assessment for haemolytic and hepatocellular disease is indicated.1 Urobilinogen levels can be increased in conditions associated with elevated nitrite levels (e.g. UTIs).1
Microscopy
Microscopy is best performed on a centrifuged specimen. 10-15mls of freshly-voided urine should be spun at 1,500-3,000 r.p.m. for five minutes, the supernatant decanted, and the sediment resuspended in the remaining liquid. A single drop is transferred to a clean glass slide and a cover slip applied.1 The sample is then examined for the following:
Cells - an excess of leucocytes suggests pyuria, but there is a gender difference. Men normally have fewer than two white blood cells (WBCs) per high power field (HPF), whilst women normally have fewer than five WBCs per HPF. The presence of transitional cells, which are small round cells with large nuclei, is normal. The presence of squamous epithelial cells, which are large irregular cells with small nuclei, suggests contamination.1 The presence of renal tubule cells indicates renal pathology.35 Dysmorphic erythrocytes may be indicative of glomerular disease.36
Casts - protein coagulum forms casts in the renal tubule, trapping any contents within them.1 RBC casts occur in glomerular bleeding, commonly in glomerulonephritis.35 The predominant cellular elements determine the type of cast: hyaline, erythrocyte, leukocyte, epithelial, granular, waxy, fatty, or broad.1,35
Crystals - these may be seen in healthy patients, but may also be helpful in assessing patients with urinary stones. Uric acid crystals are yellow to orange brown and may be diamond or barrel-shaped. Calcium oxalate crystals can vary in size, and have a refractile square 'envelope' shape. Triple phosphate crystals are colourless, have a 'coffin lid' shape, and may be associated with UTI (particularly Proteus spp.). Cysteine crystals have a hexagonal shape and are colourless.1,37 Crystals may be seen in the urinary sediment of healthy patients. Calcium oxalate crystals have a refractile square.
Bacteria - Gram staining may be helpful in specimens suspected of being contaminated, and in diagnosing the type of infection. Gram-negative rods, streptococci and staphylococci can be distinguished by their characteristic appearance under high-powered magnification.1 In women, 5 bacteria per high power field represents a count of approximately 100,000 per ml and is the standard concentration for the diagnosis of UTI in a possibly contaminated sample.1 Some authorities maintain that lower colony counts of 1,000 would be more accurate, particularly in a clean specimen.38 In men, any bacteria in a properly collected specimen is significant.34
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Document references
Simerville JA, Maxted WC, Pahira JJ; Urinalysis: a comprehensive review. Am Fam Physician. 2005 Mar 15;71(6):1153-62. [abstract]
Alper BS, Curry SH; Urinary tract infection in children. Am Fam Physician. 2005 Dec 15;72(12):2483-8. [abstract]
Tandon V, Singh H, Dwivedi US, et al; Filarial chyluria: long-term experience of a university hospital in India. Int J Urol. 2004 Apr;11(4):193-8; discussion 199. [abstract]
Marangella M; Uric acid elimination in the urine. Pathophysiological implications. Contrib Nephrol. 2005;147:132-48. [abstract]
Klahr S, Tripathy K, Bolanos O; Qualitative and quantitative analysis of urinary lipids in the nephrotic syndrome. J Clin Invest. 1967 Sep;46(9):1475-81. [abstract]
Laube N, Hoppe B, Hesse A; Problems in the investigation of urine from patients suffering from primary hyperoxaluria type 1. Urol Res. 2005 Nov;33(5):394-7. Epub 2005 Sep 8. [abstract]
Urine Specific Gravity; Medline Plus 2008
Kavouras SA; Assessing hydration status. Curr Opin Clin Nutr Metab Care. 2002 Sep;5(5):519-24. [abstract]
Steiner MJ, Nager AL, Wang VJ; Urine specific gravity and other urinary indices: inaccurate tests for dehydration. Pediatr Emerg Care. 2007 May;23(5):298-303. [abstract]
Urine PH; Rnceus 2008
Renal Tubular Acidosis; Merck Manual of Diagnosis and Therapy 2005
Shekarriz B, Stoller ML; Uric acid nephrolithiasis: current concepts and controversies. J Urol. 2002 Oct;168(4 Pt 1):1307-14. [abstract]
Akagashi K, Tanda H, Kato S, et al; Characteristics of patients with staghorn calculi in our experience. Int J Urol. 2004 May;11(5):276-81. [abstract]
Lam MH; False 'hematuria' due to bacteriuria. Arch Pathol Lab Med. 1995 Aug;119(8):717-21. [abstract]
Rao PK, Jones JS; How to evaluate 'dipstick hematuria': what to do before you refer. Cleve Clin J Med. 2008 Mar;75(3):227-33. [abstract]
Grossfeld GD, Litwin MS, Wolf JS Jr, et al; Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy--part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up. Urology. 2001 Apr;57(4):604-10.
Siegel AJ, Hennekens CH, Solomon HS, et al; Exercise-related hematuria. Findings in a group of marathon runners. JAMA. 1979 Jan 26;241(4):391-2. [abstract]
Ahmed Z, Lee J; Asymptomatic urinary abnormalities. Hematuria and proteinuria. Med Clin North Am. 1997 May;81(3):641-52. [abstract]
Mori Y, Hiraoka M, Suganuma N, et al; Urinary creatinine excretion and protein/creatinine ratios vary by body size and gender in children. Pediatr Nephrol. 2006 May;21(5):683-7. Epub 2006 Mar 21. [abstract]
Springberg PD, Garrett LE Jr, Thompson AL Jr, et al; Fixed and reproducible orthostatic proteinuria: results of a 20-year follow-up study. Ann Intern Med. 1982 Oct;97(4):516-9. [abstract]
Carroll MF, Temte JL; Proteinuria in adults: a diagnostic approach. Am Fam Physician. 2000 Sep 15;62(6):1333-40. [abstract]
Alto WA; No need for glycosuria/proteinuria screen in pregnant women. J Fam Pract. 2005 Nov;54(11):978-83. [abstract]
Rotblatt MD, Koda-Kimble MA; Review of drug interference with urine glucose tests. Diabetes Care. 1987 Jan-Feb;10(1):103-10. [abstract]
Cowart S, Stachura M; Glucosuria Clinical Methods 1990.
Nagel D, Seiler D, Hohenberger EF, et al; Investigations of ascorbic acid interference in urine test strips. Clin Lab. 2006;52(3-4):149-53. [abstract]
Hendey GW, Schwab T, Soliz T; Urine ketone dip test as a screen for ketonemia in diabetic ketoacidosis and ketosis in the emergency department. Ann Emerg Med. 1997 Jun;29(6):735-8. [abstract]
Hamdi K, Bastani P, Gafarieh R, et al; The influence of maternal ketonuria on fetal well-being tests in postterm pregnancy. Arch Iran Med. 2006 Apr;9(2):144-7. [abstract]
Mavropoulos JC, Yancy WS, Hepburn J, et al; The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: a pilot study. Nutr Metab (Lond). 2005 Dec 16;2:35. [abstract]
Toth HL, Greenbaum LA; Severe acidosis caused by starvation and stress. Am J Kidney Dis. 2003 Nov;42(5):E16-9. [abstract]
Pels RJ, Bor DH, Woolhandler S, et al; Dipstick urinalysis screening of asymptomatic adults for urinary tract disorders. II. Bacteriuria. JAMA. 1989 Sep 1;262(9):1221-4. [abstract]
Gallagher EJ, Schwartz E, Weinstein RS; Performance characteristics of urine dipsticks stored in open containers. Am J Emerg Med. 1990 Mar;8(2):121-3. [abstract]
David HL, Traore I, Feuillet A; Differential identification of Mycobacterium fortuitum and Mycobacterium chelonei. J Clin Microbiol. 1981 Jan;13(1):6-9. [abstract]
Healthcheck® Urinary Tract Infection Screening Test; Healthchem Diagnostics 2006.
Howes D; Urinary Tract Infection, Female eMedicine 2008.
Fogazzi GB, Saglimbeni L, Banfi G, et al; Urinary sediment features in proliferative and non-proliferative glomerular diseases. J Nephrol. 2005 Nov-Dec;18(6):703-10. [abstract]
Nagahama D, Yoshiko K, Watanabe M, et al; A useful new classification of dysmorphic urinary erythrocytes. Clin Exp Nephrol. 2005 Dec;9(4):304-9. [abstract]
Urinalysis; The Internet Pathology Laboratory for Medical Education 2008.; Sketches of urine casts
Cunha B; Urinary Tract Infection, Male. eMedicine 2008.
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Internet and further reading
Grossfeld GD, Litwin MS, Wolf JS Jr, et al; Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy--part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up. Urology. 2001 Apr;57(4):604-10.
Acknowledgements EMIS is grateful to Dr Laurence Knott for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 2905
Document Version: 20
DocRef: bgp657
Last Updated: 30 Sep 2008
Review Date: 30 Sep 2010
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