View source for Urinalysis

{{Short description|Array of tests performed on urine}}
{{about|the routine physical, chemical, and microscopic examination of urine|other tests performed on urine|Urine test}}
{{Infobox diagnostic
|  Name        = Urinalysis
|  Image       = Urinalysis_collage.jpg
|  Caption     = Procedures in urinalysis. Left: A [[urine test strip]] is immersed into the sample. Top right: Urine is about to be examined under a [[phase-contrast microscope]] using a Neubauer [[counting chamber]]. Bottom right: Phase-contrast microscopic image showing many [[white blood cell]]s in the urine ([[pyuria]]).
|  alt         = See caption.
|  ICD10       =
|  ICD9        
|  MeshID      = D016482
|  MedlinePlus = 003579
|  OtherCodes  = {{SearchLOINC|Urinalysis+panel+ur+-CHEM+-DRUG|LOINC Codes for Urinalysis panels}}
}}
'''Urinalysis''', a [[portmanteau]] of the words ''urine'' and ''analysis'',<ref name=oed>{{cite web|last=Harper|first=Douglas|title=Urinalysis|url=http://www.etymonline.com/index.php?term=urinalysis&allowed_in_frame=0|work=Online Etymology Dictionary|access-date=26 September 2011|url-status=live|archive-url=https://web.archive.org/web/20120821191436/http://www.etymonline.com/index.php?term=urinalysis&allowed_in_frame=0|archive-date=21 August 2012}}</ref> is a [[Test panel|panel]] of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using [[urine test strips]], and [[#Microscopic examination|microscopic examination]]. Macroscopic examination targets parameters such as color, clarity, odor, and [[specific gravity]]; urine test strips measure chemical properties such as [[pH]], [[glucose]] concentration, and [[protein]] levels; and [[microscopy]] is performed to identify elements such as [[Cell (biology)|cell]]s, [[urinary cast]]s, [[Crystalluria|crystal]]s, and [[organism]]s.{{sfn|McPherson|Pincus|2017|pp=441–3}}
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==Background==
{{multiple image
|align = left
|total_width=400
|image1=Blausen_0592_KidneyAnatomy_01.png
|alt1= Anatomical diagram of the kidney
|image2=Figure_41_03_04.jpg
|alt2= Diagram showing the structure and function of a nephron
|footer=Structure of the [[kidney]] and [[nephron]]
}}
[[Urine]] is produced by the filtration of [[blood]] in the [[kidney]]s. The formation of urine takes place in microscopic structures called [[nephrons]], about one million of which are found in a normal human kidney. Blood enters the kidney though the [[renal artery]] and flows through the kidney's vasculature into the [[Glomerulus (kidney)|glomerulus]], a tangled knot of [[capillaries]] surrounded by [[Bowman's capsule]]. The glomerulus and Bowman's capsule together form the [[renal corpuscle]]. A healthy glomerulus allows many [[solute]]s in the blood to pass through, but does not permit the passage of [[Cell (biology)|cell]]s or high-[[molecular weight]] substances such as most [[protein]]s. The [[filtrate]] from the glomerulus enters the capsule and proceeds to the [[renal tubule]]s, which reabsorb water and solutes from the filtrate into the circulation and secrete substances from the blood into the urine in order to maintain [[homeostasis]].{{sfn|Ovalle|Nahirney|2021|pp=383–9}}{{sfn|Sharp et al.|2020|pp=2–4}}

The first destination is the [[proximal convoluted tubule]]. The filtrate proceeds into the [[loop of Henle]], then flows through the [[distal convoluted tubule]] to the [[collecting duct]]. The collecting ducts ultimately drain into the [[renal calyces]], which lead to the [[renal pelvis]] and the [[ureter]]. Urine flows through the ureters into the [[bladder]] and exits the body through the [[urethra]].{{sfn|Ovalle|Nahirney|2021|pp=393–8}}{{sfn|Sharp et al.|2020|pp=5–8}} 

Besides excreting waste products, the process of urine formation helps to maintain [[Fluid balance|fluid]], [[Electrolyte balance|electrolyte]] and [[Acid–base homeostasis|acid-base balance]] in the body. The composition of urine reflects not only the functioning of the kidneys, but numerous other aspects of the body's regulatory processes.{{sfn|Turgeon|2016|pp=387–90}} The ease with which a urine sample can be obtained makes it a practical choice for diagnostic testing.{{sfn|Brunzel|2018|pp=19–22}}

==Medical uses==
Urinalysis involves assessment of the physical properties of urine, such as color and clarity; chemical analysis using [[urine test strip]]s; and microscopic examination.{{sfn|McPherson|Pincus|2017|p=441}} Test strips contain pads impregnated with chemical compounds that change color when they interact with specific elements in the sample, such as [[glucose]], [[protein]] and [[blood]],{{sfn|Turgeon|2016|pp=397–406}} and microscopic examination permits the counting and classification of solid elements of the urine, such as cells, crystals, and bacteria.{{sfn|McPherson|Pincus|2017|p=460}} 

Urinalysis is one of the most commonly performed medical laboratory tests.{{sfn|Van Leeuwen|Bladh|2019|p=1199}} It is frequently used to help diagnose [[urinary tract infection]]s{{sfn|Sharp et al.|2020|p=98}} and to investigate other issues with the [[urinary system]], such as [[Urinary incontinence|incontinence]].{{sfn|Rakel|Rakel|2016|p=49}} It may be used to [[Screening (medicine)|screen]] for diseases as part of a medical assessment. The results can suggest the presence of conditions such as [[kidney disease]], [[liver disease]] and [[diabetes]].{{sfn|Van Leeuwen|Bladh|2019|p=1199}} In [[emergency medicine]] urinalysis is used to investigate numerous symptoms, including [[abdominal pain|abdominal]] and [[pelvic pain]],{{sfn|Walls|Hockberger|Gausche-Hill|2017|p=219}}{{sfn|Walls|Hockberger|Gausche-Hill|2017|p=266}} [[fever]],{{sfn|Walls|Hockberger|Gausche-Hill|2017|p=101}} and [[confusion]].{{sfn|Walls|Hockberger|Gausche-Hill|2017|p=135}} During [[pregnancy]], it may be performed to screen for protein in the urine ([[proteinuria]]), which can be a sign of [[pre-eclampsia]],<ref name="NICE">{{cite web|title=Antenatal care|url=https://www.nice.org.uk/guidance/ng201/chapter/Recommendations#routine-antenatal-clinical-care|work=[[National Institute for Health and Care Excellence]]|date=2021|id=Guideline NG201|archiveurl=https://web.archive.org/web/20220711222939/https://www.nice.org.uk/guidance/ng201/chapter/Recommendations|accessdate=28 July 2022|archivedate=11 July 2022|url-status=live}}</ref> and [[Bacteriuria|bacteria in the urine]], which is associated with pregnancy complications.{{sfn|Walls|Hockberger|Gausche-Hill|2017|p=266}}<ref name="kalinderi">{{cite journal|last1=Kalinderi|first1=K.|last2=Delkos|first2=D.|last3=Kalinderis|first3=M.|last4=Athanasiadis|first4=A.|last5=Kalogiannidis|first5=I.|date=2018|title=Urinary tract infection during pregnancy: current concepts on a common multifaceted problem|journal=Journal of Obstetrics and Gynaecology|volume=38|issue=4|pages=448–453|doi=10.1080/01443615.2017.1370579|pmid=29402148 |s2cid=46856646 }}</ref> The analysis of urine is invaluable in the diagnosis and management of kidney diseases.{{sfn|Rifai|Horvath|Wittwer|2018|pp=479–80}}

==Specimen collection==
Samples for urinalysis are collected into a clean (preferably sterile) container.{{sfn|Brunzel|2018|pp=19–22}}<ref name="bardsley"/> The sample can be collected at any time of the day,{{sfn|Brunzel|2018|p=20}} but the first urine of the morning is preferred because it is more concentrated.<ref name="echeverry"/> To prevent contamination, a "midstream clean-catch" technique is recommended, in which the genital area is cleaned before urinating and the sample is collected partway through the urination.<ref name="bardsley">{{cite journal|last=Bardsley|first=A.|date=2015|title=How to perform a urinalysis|journal=[[Nursing Standard]]|volume=30|issue=2|pages=34–36 |doi=10.7748/ns.30.2.34.e10001|pmid=26350868 |url=https://pure.coventry.ac.uk/ws/files/3936273/bardsley1comb.pdf }}</ref> Samples can also be collected from a [[urinary catheter]] or by inserting a needle through the abdomen and into the bladder ([[suprapubic aspiration]]).{{sfn|McPherson|Pincus|2017|p=443}} In infants and young children, urine may be collected into a bag attached to the genital region, but this is associated with a high risk of contamination.{{sfn|Brunzel|2018|pp=19–22}} If the sample is not tested promptly, inaccurate results can occur because bacteria in the urine will multiply and elements such as cells and [[Urinary cast|casts]] will degrade. It is recommended that urinalysis is performed within two hours of sample collection if the urine is not refrigerated.<ref name="echeverry"/>

==Macroscopic examination==
===Color and clarity===
{{See also|Urine#Color}}
[[File:Urine samples of varying colour and clarity.jpg|thumb|upright=1.2|alt=A variety of urine samples in a test tube rack. From left to right, the color and clarity of each  sample is: clear and dark yellow; clear and pale yellow; orange and cloudy; red and cloudy; pinkish-yellow and cloudy.|Urine samples of varying color and clarity]]
Normal urine has a yellow hue, which is primarily caused by the pigment [[urochrome]]. The color can range from pale yellow to amber based on the individual's hydration status. Urine can develop a variety of abnormal colors, which may suggest disease in some cases.{{sfn|Haber et al.|2010|pp=38–9}} A total lack of color indicates that the urine is extremely dilute, which may be caused by excessive fluid intake, [[diabetes insipidus]], or [[diabetes mellitus]]. Dark yellow-brown to green urine may suggest a high concentration of [[bilirubin]], a state known as [[bilirubinuria]].{{sfn|Haber et al.|2010||pp=38–9}}{{sfn|McPherson|Pincus|2017|p=444}} Red urine often indicates the presence of [[red blood cells]] or [[hemoglobin]], but can also be caused by  some medications and the consumption of foods containing red pigments,{{sfn|Haber et al.|2010||pp=38–9}} such as [[beets]]. [[Myoglobin]], a product of muscle breakdown, can give urine a red to reddish-brown color.{{sfn|McPherson|Pincus|2017|p=443–4}} Dark brown or black urine can occur in a genetic disorder called [[alkaptonuria]] and in people with [[melanoma]].{{sfn|Mundt|Shanahan|2016|p=80}} Purple urine occurs in [[purple urine bag syndrome]].<ref name="kang">{{cite journal|last1=Kang|first1=K.H.|last2=Jeong|first2=K.H.|last3=Baik|first3=S.K.|last4=Huh|first4=W.Y.|last5=Lee|first5=T.W.|last6=Ihm|first6=C.G.|last7=Lee|first7=S.H.|last8=Moon|first8=J.Y.|display-authors=6|date=2011|title=Purple urine bag syndrome: case report and literature review|journal=Clinical Nephrology|volume=75|issue=6|pages=557–559|doi=10.5414/cn106615|pmid=21612761 }}</ref>

A spectrum of abnormal colors can result from the intake of drugs. An unusually bright yellow color can occur after consumption of [[B vitamin]] supplements,{{sfn|Brunzel|2018|p=70}} while [[phenazopyridine]], used to treat urinary tract-related pain, can turn the urine orange. [[Methylene blue]] may turn it blue to bluish-green.{{sfn|Mundt|Shanahan|2016||pp=80–1}} [[Phenolphthalein]], a stimulant [[laxative]] previously found in [[Ex-Lax]],<ref name="murphy">{{cite journal|title=Movement Away From Phenolphthalein in Laxatives|first=James|last=Murphy|date=6 May 2009|journal=JAMA|volume=301|issue=17|pages=1770|doi=10.1001/jama.2009.585|pmid=19417193}}</ref> can produce colors ranging from red to purple, and [[levodopa]], used to treat [[Parkinson's disease]], may result in "cola-colored" urine.{{sfn|McPherson|Pincus|2017|p=444}}

The clarity of urine is also recorded during urinalysis. Urine is typically clear; materials such as crystals, cells, bacteria, and mucus can impart a cloudy appearance.{{sfn|Haber et al.|2010|pp=38–9}} A milky appearance can be caused by a very high concentration of white blood cells or [[lipiduria|fats]], or by [[chyluria]] (the presence of [[lymphatic fluid]] in the urine).{{sfn|McPherson|Pincus|2017|pp=444–5}} Unpreserved urine will become cloudier over time.{{sfn|Mundt|Shanahan|2016|p=76}}

===Smell===
{{See also|Urine#Odor}}
The odor (scent) of urine can normally vary from odorless (when very light colored and dilute) to a much stronger odor when the subject is dehydrated and the urine is concentrated.<ref>{{cite web|url=http://www.mayoclinic.org/symptoms/urine-odor/basics/causes/sym-20050704|title=Urine odor Causes|website=mayoclinic.org|access-date=30 April 2018|url-status=live|archive-url=https://web.archive.org/web/20180109031228/https://www.mayoclinic.org/symptoms/urine-odor/basics/causes/sym-20050704|archive-date=9 January 2018}}</ref>  Transient changes in urine odor can occur after consuming certain foods, most notably [[asparagus]]. The urine of diabetics experiencing [[ketoacidosis]] (urine containing high levels of [[ketone]] bodies) may have a fruity or sweet smell, while urine from individuals with [[urinary tract infection]]s often has a foul smell. Some [[inborn errors of metabolism]] cause characteristic odors, such as [[maple syrup urine disease]] (which takes its name from the urine scent) and [[phenylketonuria]] (which causes a "mousey" smell).{{sfn|Haber et al.|2010|p=39}} Odor is rarely reported during urinalysis.{{sfn|Mundt|Shanahan|2016|p=83}}

===Specific gravity===
[[Urine specific gravity|Specific gravity]] is a measure of the concentration of the urine, which provides information about hydration status and kidney function. It normally ranges from 1.003 to 1.035; lower values indicate that the urine is dilute, while higher values mean that it is concentrated. A urine specific gravity that consistently remains around 1.010 ([[isosthenuria]]) can indicate kidney damage, as it suggests that the kidneys have lost the ability to control urine concentration.{{sfn|Turgeon|2016|p=396}} It is not possible for the kidneys to produce urine with a specific gravity greater than 1.040{{sfn|Brunzel|2018|p=78}} but such readings can occur in urine that contains high-[[molecular weight]] substances, such as [[contrast dye]]s used in [[Radiography|radiographic imaging]].{{sfn|Mundt|Shanahan|2016|p=83}} Specific gravity is commonly measured with [[urine test strip]]s, but [[refractometer]]s may also be used.{{sfn|Turgeon|2016|p=397}} Reagent strip readings are based on the concentration of [[ion]]s in the sample, while refractometer readings are affected by other substances such as glucose and protein.{{sfn|Brunzel|2018|p=77}}

==Urine test strip==
{{main|Urine test strip}}
[[File:Urine_Quicktest.jpg|thumb|alt=A test strip with numerous colored pads is placed next to its container, which is labelled with a chart demonstrating how the color changes correspond to test results.|A [[urine test strip]] is compared against a color chart to determine the results.]]
[[Urine test strip]]s or "dipsticks" allow for the rapid measurement of numerous urine parameters and substances. The strip is dipped into the urine sample and the color changes on the reagent pads are read after a defined period of time, either by eye or using an automated instrument.{{sfn|Turgeon|2016|p=397−8}} The tests included vary depending on the type of dipstick, but common ones are [[glucose]], [[ketones]], [[bilirubin]], [[urobilinogen]], blood, white blood cells ([[leukocyte esterase]]), [[Urine protein|protein]], [[nitrite]], [[pH]], and [[specific gravity]].{{sfn|Turgeon|2016|pp=406–412}}{{sfn|Rifai|Horvath|Wittwer|2018|p=480}} Nitrite is reported as negative or positive;{{sfn|Brunzel|2018|p=103}} other elements may be scored on a scale or reported as an approximate concentration based on the intensity of the color change.{{sfn|Turgeon|2016|p=398}}

False positive and false negative results may occur. General sources of error include abnormally colored urine, which interferes with the interpretation of color changes;{{sfn|Brunzel|2018|p=89}} high levels of [[ascorbic acid]] (Vitamin C), which can cause false negative results for blood, bilirubin, glucose, and nitrite;{{sfn|Brunzel|2018|pp=116–7}} and variations in the concentration of the sample.<ref name="delanghe"/>

===Blood===
Reagent pads for blood change color in the presence of [[heme group]]s, which [[catalyze]] the reaction of [[hydrogen peroxide]] with the color indicator in the test strip. Heme groups are found in [[hemoglobin]], but also in [[myoglobin]] (a product of muscle breakdown). Thus, a positive result for blood can represent the presence of red blood cells ([[hematuria]]), free hemoglobin ([[hemoglobinuria]]), or myoglobin ([[myoglobinuria]]).<ref name="Kavuru">{{cite journal|first1=V.|last1=Kavuru|first2=T.|last2=Vu|first3=L.|last3=Karageorge|first4=D.|last4=Choudhury|first5=R.|last5=Senger|first6=J.|last6=Robinson|date=2019|title=Dipstick analysis of urine chemistry: benefits and limitations of dry chemistry-based assays|journal=[[Postgraduate Medicine]]|doi=10.1080/00325481.2019.1679540|volume=132|issue=3|pages=225–233|pmid=31609156 |s2cid=204545636 }}</ref> Red blood cells can sometimes be distinguished from free hemoglobin or myoglobin as the former causes a speckled pattern on the test pad while the latter results in a uniform color change.{{sfn|Mundt|Shanahan|2016|p=98}}

===White blood cells===
[[Leukocyte esterase]], an [[enzyme]] found in [[granulocyte]]s, is measured to estimate the concentration of [[white blood cell]]s.{{sfn|Turgeon|2016|p=405}} The action of the enzyme on chemicals in the test pad ends in the creation of a purple [[azo dye]].{{sfn|Brunzel|2018|pp=101–2}} False positive results can occur if the sample is contaminated with vaginal secretions; false negatives can occur in very concentrated samples or those containing high levels of [[glucose]] and [[protein]].{{sfn|Brunzel|2018|pp=101–2}}  Elevated white blood cell counts in urine generally indicate infection or inflammation.{{sfn|McPherson|Pincus|2017|pp=405–6}} People with a low level of neutrophils in the blood ([[neutropenia]]) may not have enough white blood cells in their urine to produce a positive reaction.{{sfn|Van Leeuwen|Bladh|2019|p=1200}}

===Nitrite===
Some bacteria that cause UTIs can [[Reduction (chemistry)|reduce]] urinary [[nitrate]]s to [[nitrite]]s. The presence of nitrites, which causes a pink color on the reagent strip pad, therefore acts as an indicator of urinary tract infection.<ref name="Kavuru"/> The nitrite test is quite [[Specificity and sensitivity|specific]], meaning that someone is likely to have a UTI if it is positive, but it is not sensitive; a negative result does not reliably indicate that the subject does not have a UTI.<ref name="takhar">{{cite journal|first1=S.S. |last1=Takhar|first2=G.J.|last2=Moran|title=Diagnosis and Management of Urinary Tract Infection in the Emergency Department and Outpatient Settings|journal=[[Infectious Disease Clinics of North America]]|volume=28|issue=1|date=2014|pages=33–48|doi=10.1016/j.idc.2013.10.003|pmid=24484573 }}</ref><ref name="meister">{{cite journal|first1=L.|last1=Meister|first2=E.J.|last2=Morley|first3=D.|last3=Scheer|first4=R.|last4=Sinert|title=History and physical examination plus laboratory testing for the diagnosis of adult female urinary tract infection|journal=[[Academic Emergency Medicine]]|date=2013|volume=20|issue=7|doi=10.1111/acem.12171|pages=631–645|pmid=23859578 |doi-access=free}}</ref> Not all bacteria that cause UTIs produce nitrite, and because it takes time for the chemical reaction to occur, the test is best performed on urine that has been in the bladder overnight.{{sfn|McPherson|Pincus|2017|pp=457–8}} A diet low in vegetables can lead to low nitrate levels in the urine, meaning that nitrites cannot be produced.<ref name="delanghe">{{cite journal|last1=Delanghe|first1=J.R.|last2=Speeckaert|first2=M.M.|title=Preanalytics in urinalysis|journal=Clinical Biochemistry|date=2016|volume=49|issue=18|pages=1346–1350|doi=10.1016/j.clinbiochem.2016.10.016|pmid=27784640 }}</ref> False positive results can occur in samples that are contaminated or stored improperly, allowing bacteria to multiply.{{sfn|McPherson|Pincus|2017|pp=457–8}}

===Protein===
Test strips estimate urine protein levels by exploiting the ability of protein to interfere with [[pH indicator]]s. The reagent pad contains an indicator that is [[Buffer (chemistry)|buffered]] to a pH of 3, which changes from yellow to green in the presence of protein.{{sfn|Rifai|Horvath|Wittwer|2018|p=480}} Trace levels of protein in the urine can be normal,{{sfn|McPherson|Pincus|2017|p=450}} but high levels ([[proteinuria]]) can indicate kidney disease.{{sfn|Rifai|Horvath|Wittwer|2018|p=480}} Most cases of proteinuria are caused by increased levels of [[albumin]],{{sfn|Rifai|Horvath|Wittwer|2018|p=487}} which test strips can detect relatively well; but they are markedly less sensitive to other proteins, such as [[Bence-Jones protein]],<ref name="resimont">{{cite journal|last1=Résimont|first1=G.|last2=Piéroni|first2=L.|last3=Bigot-Corbel|first3=E.|first4=E.|last4=Cavalier|first5=P.|last5=Delanaye|title=Urinary strips for protein assays: easy to do but difficult to interpret!|journal=Journal of Nephrology|volume=34|pages=411–432|date=2021|issue=2 |doi=10.1007/s40620-020-00735-y|pmid=32328900 |s2cid=216075968 }}</ref> which may occur in [[multiple myeloma]].{{sfn|Bain|2015|p=470}} Because the test pad reaction is dependent on pH, false positive results can occur if the urine is highly alkaline.{{sfn|McPherson|Pincus|2017|p=450}}<ref name="resimont"/> Conventional test strips are not sensitive enough to reliably detect [[microalbuminuria]], a condition in which urine albumin levels are slightly elevated,{{sfn|Brunzel|2018|p=95}} although dipsticks specialized for this measurement exist.<ref name="resimont"/>

===pH===
[[pH indicators]] are used to measure the pH of the sample. Urine pH varies with diet and a wide range of values occur in healthy subjects, although it is most commonly slightly acidic. Because the kidneys are involved in regulating acid-base balance, the urine is typically acidic in people with [[Metabolic acidosis|metabolic]] or [[respiratory acidosis]] and alkaline in those with [[alkalosis]]. However, in [[renal tubular acidosis]], the urine pH remains alkaline while the blood is acidic.{{sfn|Partin et al.|2021|p=16}}{{sfn|McPherson|Pincus|2017|p=447}} During urinary tract infections, waste products of bacterial metabolism can cause the urine to become alkaline.{{sfn|Brunzel|2018|p=90}} Urine pH may be monitored to help prevent the formation of [[kidney stone]]s or to avoid side effects of some drugs,{{sfn|Turgeon|2016|p=400}} such as high-dose [[methotrexate]] therapy, in which crystals that cause kidney damage can form if the urine is acidic.<ref name="Howard">{{cite journal|last1=Howard|first1=S.C.|last2=McCormick|first2=J.|last3=Pui|first3=C.H.|last4=Buddington|first4=R.K.|last5=Harvey|first5=R.D.|title=Preventing and Managing Toxicities of High-Dose Methotrexate|journal=The Oncologist|volume=21|issue=12|pages=1471–1482|doi=10.1634/theoncologist.2015-0164|date=2016|pmid=27496039 |pmc=5153332 }}</ref> If microscopy is performed, knowing the pH of the sample helps to identify any crystals that might be present.{{sfn|Turgeon|2016|p=400}}

===Specific gravity===
Urine test strips use the concentration of [[ion]]s in the urine to estimate specific gravity. The test pad contains a [[polyelectrolyte]] that releases [[hydrogen]] ions in proportion to the concentration of ions in the sample. The consequent pH change is measured using a pH indicator. The reading obtained from reagent strips, as opposed to refractometers, is not affected by substances such as [[glucose]], [[urea]] and contrast dyes. Falsely low readings can occur in alkaline urine.{{sfn|Mundt|Shanahan|2016|pp=85–6}}{{sfn|McPherson|Pincus|2017|p=446}}

===Glucose===
Test strips for glucose contain the enzyme [[glucose oxidase]], which breaks down glucose and forms [[hydrogen peroxide]] as a byproduct. In the presence of a [[peroxidase]] enzyme, hydrogen peroxide reacts with a [[chromogen]] to induce a color change.<ref name="Kavuru"/> The presence of glucose in the urine is known as [[glycosuria]]. In people with normal blood sugar levels, the amount of glucose in the urine should be negligible as it is reabsorbed by the renal tubules.{{sfn|Sharp et al.|2020|p=119}} High blood sugar levels ([[hyperglycemia]]) cause excess glucose to spill over into the urine and result in a positive reading. This characteristically occurs in [[diabetes mellitus]]{{sfn|Rakel|Rakel|2016|p=970}} (although it is not part of the formal diagnostic criteria).{{sfn|Rifai|Horvath|Wittwer|2018|p=482}} Glycosuria may occur in people with normal blood sugar levels during pregnancy or due to dysfunction of the renal tubules (termed [[renal glycosuria]]).{{sfn|Sharp et al.|2020|p=121}}

===Ketones===
[[File:Ketonuria.jpg|thumb|alt=A test strip with a single pad is held up to a color chart on the test strip container. The test strip is a deep purple color, which corresponds to a result of 3+.|Positive result on a [[Ketostix]] test strip, which is specialized for measuring ketones]]
[[Ketone bodies]] are products of [[fat]] breakdown. When the body relies on fats, rather than [[carbohydrates]], as its main energy source, increased levels of ketones occur in the blood and urine. The presence of detectable levels of ketones in the urine is called [[ketonuria]]. Ketones occur in three forms in the body: [[beta-hydroxybutyrate]] (BHB), [[acetone]] and [[acetoacetate]]. Test strips use [[sodium nitroprusside]] to detect [[acetoacetate]], and those with a [[glycine]] additive can detect [[acetone]]; however, none detect BHB. The reaction of ketones with sodium nitroprusside in an alkaline medium turns the test pad purple.{{sfn|Turgeon|2016|pp=408–9}}

Ketonuria occurs in uncontrolled [[type 1 diabetes]] and in [[diabetic ketoacidosis]].{{sfn|Sharp et al.|2020|pp=124–6}} Ketonuria can also occur when the body's demand for carbohydrates outpaces dietary intake, such as in people following a [[ketogenic diet]], people experiencing severe [[vomiting]] or [[diarrhea]], and during [[starvation]]{{sfn|Turgeon|2016|p=409}} or after strenuous exercise. Mild ketonuria can be normal during pregnancy.{{sfn|McPherson|Pincus|2017|p=453}} Some medications, such as [[levodopa]] or [[methyldopa]], can cause a false positive result.{{sfn|Sharp et al.|2020|p=125}}

===Bilirubin===
[[Bilirubin]] is a waste product formed from the breakdown of [[hemoglobin]]. Cells of the [[mononuclear phagocyte system]] digest aged red blood cells and release [[unconjugated bilirubin]] into the bloodstream, which is converted to water-soluble [[conjugated bilirubin]] by the [[liver]]. Conjugated bilirubin is normally stored in the [[gallbladder]] as a constituent of [[bile]] and is excreted through the [[intestine]]s; it does not occur at detectable levels in the urine.{{sfn|Turgeon|2016|pp=409–12}}

The presence of bilirubin in the urine (termed [[bilirubinuria]]) occurs as a consequence of high blood levels of conjugated bilirubin in [[liver disease]] or [[Obstructive jaundice|bile duct obstruction]]. Bilirubin is detected by means of reaction with a [[diazonium]] salt that forms a colored complex. With prolonged light exposure, bilirubin converts to [[biliverdin]] and becomes undetectable by reagent strips.{{sfn|Sharp et al.|2020|pp=136–7}}

===Urobilinogen===
[[Urobilinogen]] refers to a group of compounds produced from bilirubin by the [[intestinal flora]]. Under normal conditions, most of the urobilinogen produced is absorbed into the bloodstream and secreted into the bile by the liver, or excreted in the [[feces]] as [[stercobilin]] and other compounds. A small fraction is excreted in the urine.{{sfn|Turgeon|2016|p=410}}{{sfn|Rifai|Horvath|Wittwer|2018|p=767}}

Urine urobilinogen is increased in liver disease and [[hemolytic jaundice]] (jaundice due to increased destruction of red blood cells); in the latter case, urine bilirubin is typically negative. In bile duct obstruction, urine bilirubin increases but urobilinogen is normal or decreased, as bilirubin cannot reach the intestines to be converted to urobilinogen.{{sfn|Sharp et al.|2020|pp=138–9}} Testing methods are based on the [[Ehrlich's reagent|Ehrlich reaction]] of urobilinogen with [[Para-dimethylaminobenzaldehyde|''para''-dimethylaminobenzaldehyde]], or interaction with a diazonium compound to produce a colored product. Test strips that use Ehrlich's reagent can give false positive results in the presence of [[porphobilinogen]] and numerous drugs.{{sfn|McPherson|Pincus|2017|p=457}} Decreased levels of urobilinogen cannot be detected by the dipstick method. Like bilirubin, urobilinogen is sensitive to light.{{sfn|Brunzel|2018|pp=114–6}}

==Microscopic examination==
[[File:Formed elements of urine.png|thumb|upright=1.9|left|alt=See caption.|Microscopic view of various elements of the urine; (i) [[Squamous epithelium|squamous epithelial cells]], (ii) [[red blood cells]], (iii) [[white blood cells]], (iv) [[bacteria]], (v) [[yeast]], (vi) [[calcium oxalate]] crystals, (vii) triple phosphate crystals, (viii) [[granular cast]]s, and (ix) yeast with [[pseudohyphae]]<ref>{{cite journal|last=Lehmann|first=R.|title=From bedside to bench-practical considerations to avoid pre-analytical pitfalls and assess sample quality for high-resolution metabolomics and lipidomics analyses of body fluids.|journal=[[Analytical and Bioanalytical Chemistry]]|date=2021|volume=413|issue=22|pages=5567–5585|doi=10.1007/s00216-021-03450-0|pmid=34159398 |pmc=8410705 }}</ref>]]
Microscopic examination of the urine allows [[cell (biology)|cell]]s and elements such as [[urinary casts]] to be identified and counted. This can yield a great detail of information and may suggest a specific diagnosis. Microscopy is not always included in urinalysis: it may be reserved for samples that have abnormal results on preliminary testing or that are from certain patient populations, such as infants.{{sfn|Turgeon|2016|p=413}} Results that typically require microscopic examination include abnormal color or clarity and positive dipstick results for blood, leukocytes, nitrite, or protein.{{sfn|Brunzel|2018|p=117}}

If microscopy is necessary, the urine may be [[centrifuge]]d to concentrate the solid elements so that they can be viewed more easily. In this case, a drop of the concentrated sample is placed under a [[coverslip]] and examined, typically at 100x and 400x [[magnification]].{{sfn|Turgeon|2016|pp=414–5}} The microscopic components of urine are reported according to the amount present in the microscope's field of view at low magnification (reported as /lpf, meaning low-power field) and high magnification (/hpf for high-power field). Some elements, such as crystals or bacteria, are typically reported in a [[wikt:qualitative|qualitative]] format, using terms such as "few" or "many" or grades from 1+ to 4+. Others, such as cells or casts, are reported using numerical ranges.{{sfn|Brunzel|2018|p=130}} If it is necessary to determine the exact number of cells or casts in the sample, unconcentrated urine can be placed in a counting chamber called a [[hemocytometer]]. In this case, the results are reported per microliter (/μL).{{sfn|McPherson|Pincus|2017|p=461}} Urine is traditionally examined by [[light microscopy]], but some laboratories use [[phase-contrast microscope]]s, which improve the visualization of elements such as [[urinary casts]] and mucus. Urine can also be [[Supravital stain|stained]] before analysis to make its components easier to identify.{{sfn|Turgeon|2016|pp=414–5}}

There are automated microscopy systems that use [[flow cytometry]] technology or pattern recognition to identify microscopic elements in unconcentrated urine.<ref name="OyaertDelanghe2019">{{cite journal|last1=Oyaert|first1=Matthijs|last2=Delanghe|first2=Joris|title=Progress in Automated Urinalysis|journal=Annals of Laboratory Medicine|volume=39|issue=1|year=2019|pages=15–22|issn=2234-3806|doi=10.3343/alm.2019.39.1.15|pmid=30215225|pmc=6143458|doi-access=free}}</ref> Automated instruments reduce workload in medical laboratories and can accurately identify most common urinary elements, but do not perform as well with unusual findings such as transitional and renal epithelial cells, abnormal casts and rare crystals.<ref name="Becker2016">{{cite journal|last1=Becker|first1=G.J.|last2=Garigali|first2=G.|last3=Fogazzi|first3=G.B|title=Advances in Urine Microscopy|journal=American Journal of Kidney Diseases|date=2016|volume=67|issue=6|pages=954–64|doi=10.1053/j.ajkd.2015.11.011|pmid=26806004 }}</ref>

Elements that can be observed on microscopic examination include:

===Red blood cells===
[[File:Pus cells, Epithelial cells, RBCs and Bacteria in Urine Microscopy.jpg|thumb|upright=1.3|alt=See caption.|[[Light microscopy]] image showing squamous epithelial cells, white blood cells, and red blood cells in urine. Bacteria are also visible.]]
Under the microscope, normal red blood cells (RBCs) appear as small concave discs. Their numbers are reported per high-power field.{{sfn|Brunzel|2018|p=137}} In highly concentrated urine they may shrivel and develop a spiky shape, which is termed ''crenation'', while in dilute urine they can swell and lose their [[hemoglobin]], creating a faint outline known as a ''ghost cell''. A small quantity of red blood cells in the urine is considered normal.{{sfn|McPherson|Pincus|2017|p=461}}{{sfn|Brunzel|2018|p=138}}

An increased level of RBCs is termed [[hematuria]]. Microscopic hematuria is sometimes observed in healthy people after exercise<ref name="afp2022">{{cite journal|last1=Hitzeman|first1=N.|last2=Greer|first2=D.|last3=Carpio|first3=E.|date=2022|title=Office-Based Urinalysis: A Comprehensive Review|journal=[[American Family Physician]]|volume=106|issue=1|pages=27–35B|pmid=35839369}}</ref> or as a consequence of contamination of the sample with [[menstrual blood]].{{sfn|Brunzel|2018|p=138}} Pathologic causes of hematuria are diverse and include trauma to the urinary tract, [[kidney stone]]s, [[urinary tract infection]]s, [[drug toxicity]], [[genitourinary]] cancers, and a variety of other renal and systemic diseases.{{sfn|McPherson|Pincus|2017|p=461}}{{sfn|Brunzel|2018|p=139}}<ref name="afp2022"/> Abnormally shaped red blood cells with blob-like protrusions of the cell membrane, called dysmorphic RBCs, are thought to represent damage to the [[Glomerulus (kidney)|glomerulus]].{{sfn|Brunzel|2018|pp=137–8}}<ref name="peterson">{{cite journal|last1=Peterson|first1=L.M.|last2=Reed|first2=H.S.|title=Hematuria|date=2019|journal=Primary Care: Clinics in Office Practice|volume=46|issue=2|pages=265–273 |doi=10.1016/j.pop.2019.02.008|pmid=31030828 |s2cid=243594433 }}</ref>

===White blood cells===
Typically, most white blood cells (WBCs) in urine are [[neutrophil]]s. They are round, larger than RBCs, possess a [[cell nucleus]], and have a granular appearance. A few white blood cells can normally be found in the urine of healthy individuals; females tend to have slightly more than males. An increased number of WBCs is termed [[pyuria]] or [[leukocyturia]] and is associated with infection or inflammation of the urinary tract. WBCs can also appear in the urine following exercise or [[fever]].{{sfn|McPherson|Pincus|2017|pp=461–2}} An increased number of [[eosinophil]]s ([[eosinophiluria]]) can occur in [[acute interstitial nephritis]] and chronic UTIs. [[Cytocentrifugation]] and staining of the urine sample is necessary to reliably distinguish eosinophils from neutrophils.{{sfn|Brunzel|2018|p=141}}

===Epithelial cells===
{{Further|Urine cytology}}
[[Epithelial cells]] form the lining of the [[urinary tract]]. Three types may occur in urine: [[squamous epithelial cells]], [[Transitional epithelium|transitional epithelial cells]] and renal tubular epithelial cells. Some laboratories do not distinguish between the three types of cells and simply report "epithelial cells" in general.{{sfn|Mundt|Shanahan|2016|pp=115–6}}

Squamous epithelial cells line the [[urethra]], as well as the [[vagina]] and the outer layer of the skin. They are very large, flat, and thin, with irregular borders and a single, small [[Cell nucleus|nucleus]]. They may fold into various shapes. They are not considered clinically significant, but if they are seen in large numbers they can indicate contamination of the sample by vaginal secretions or the skin of the urogenital area.{{sfn|Turgeon|2016|pp=420–1}}{{sfn|Brunzel|2018|pp=143–5}}

Transitional epithelial cells, also known as urothelial cells, line the urinary tract from the [[renal pelvis]] through the [[ureter]]s and [[bladder]] and, in males, the upper ([[proximal]]) portion of the urethra. They are smaller than squamous cells and their shape varies based on the layer of epithelium from which they are derived, but they are most commonly round or pear-shaped.{{sfn|Brunzel|2018|pp=143–5}} They may have one or two nuclei.{{sfn|Mundt|Shanahan|2016|pp=115–6}} Small numbers of these cells are found in normal urine; larger numbers can be seen after invasive procedures like [[catheterization]] or [[cystoscopy]] or in conditions that irritate the urinary tract, such as [[urinary tract infection]]s.{{sfn|Brunzel|2018|p=45}} In the absence of recent trauma to the urinary tract, clusters and sheets of transitional cells in the urine may indicate [[malignancy]], requiring further investigation.{{sfn|McPherson|Pincus|2017|pp=462–3}}

Renal tubular epithelial cells (RTEs) line the [[collecting duct]]s and the [[Distal tubule|distal]] and [[proximal tubule]]s of the [[kidney]].{{sfn|Brunzel|2018|pp=146–8}} They can be difficult to identify in unstained urine, as they look similar to urothelial cells and WBCs;{{sfn|Turgeon|2016|p=421}} however, they are generally larger than WBCs and smaller than urothelial cells,{{sfn|Mundt|Shanahan|2016|pp=115–6}} and collecting duct cells, unlike urothelial cells, often have a flat edge.{{sfn|Turgeon|2016|p=421}} The presence of RTEs in high numbers is a significant finding, as this indicates damage to the [[renal tubule]]s. This may occur in conditions such as [[acute tubular necrosis]], drug or [[heavy metal toxicity]], [[acute glomerulonephritis]], kidney [[transplant rejection]], trauma, and [[sepsis]].{{sfn|Brunzel|2018|pp=146–8}}{{sfn|McPherson|Pincus|2017|p=463}}

===Casts===
[[File:RTE cast, muddy granular cast, WBC cast and RBC cast in urine.jpg|thumb|upright=1.2|left|Examples of [[urinary casts]]: a) RTE cell cast, b) "muddy" granular cast, c) white blood cell cast, d) red blood cell cast<ref name="mohsenin">{{cite journal|last=Mohsenin|first=V.|title=Practical approach to detection and management of acute kidney injury in critically ill patient|journal=Journal of Intensive Care|date=2017|volume=5|page=57|doi=10.1186/s40560-017-0251-y|pmid=28932401 |pmc=5603084 |doi-access=free }}</ref>]]
[[Urinary casts]] are cylindrical structures composed of [[Tamm-Horsfall glycoprotein]]. Their shape derives from the [[renal tubules]] where they are formed, and the protein base can incorporate cells or other material. Hyaline casts contain only protein and can be found in low numbers in healthy people; their numbers may increase transiently after exercise or dehydration. Persistently increased numbers are seen in many renal diseases.{{sfn|Mundt|Shanahan|2016|p=129}} They are almost transparent and can be difficult to see using light microscopy.{{sfn|Turgeon|2016|p=423}}

Granular casts, so named for their microscopic appearance, incorporate degenerated cellular material or protein aggregates. They are considered an abnormal finding and are associated with diseases of the kidney<ref name="callefi">{{cite journal|last1=Caleffi|first1=A.|last2=Lippi|first2=G.|date=2015|title=Cylindruria|journal=[[Clinical Chemistry and Laboratory Medicine]]|volume=53|issue=Suppl 2|pages=1471–s1477|doi=10.1515/cclm-2015-0480|pmid=26079824 |s2cid=263857666 |doi-access=free}}</ref> although they can rarely occur in healthy individuals, particularly following strenuous physical activity.{{sfn|Brunzel|2018|p=151}} Large, dense casts with cracked edges, called waxy casts, are traditionally associated with [[chronic kidney failure]],{{sfn|Brunzel|2018|p=154}} though little evidence exists to support this.<ref name="callefi"/> Red blood cell casts incorporate intact RBCs and are a serious finding because under normal conditions, RBCs cannot pass through the [[Glomerulus (kidney)|glomerulus]] into the renal tubules.{{sfn|McPherson|Pincus|2017|p=465}} These casts are characteristically found in people with glomerular diseases such as [[acute glomerulonephritis]] and [[lupus nephritis]].{{sfn|Turgeon|2016|p=425}} White blood cell casts represent infection or inflammation involving the kidneys;{{sfn|Mundt|Shanahan|2016|p=130}} they can occur in [[pyelonephritis]], but are absent in lower urinary tract infections.{{sfn|Turgeon|2016|p=424}} Following injury to the renal tubules, renal tubular epithelial cell casts may be seen in the urine.{{sfn|Brunzel|2018|p=155}}  Casts may incorporate a variety of other materials such as bacteria, yeast, crystals, and pigments like bilirubin or myoglobin.<ref name="callefi"/>

===Crystals===
{{main|Crystalluria}}
[[File:Urine crystals comparison.png|thumb|Comparison of different types of urine crystals.]]
Various compounds in the urine can [[Precipitation (chemistry)|precipitate]] to form crystals. Crystals can be identified based on their appearance and the pH of the urine (many types preferentially form at an acidic or alkaline pH).{{sfn|McPherson|Pincus|2017|p=467}} Crystals that can be found in normal urine include [[uric acid]], monosodium urate, triple phosphate ([[ammonium magnesium phosphate]]), [[calcium oxalate]], and [[calcium carbonate]].{{sfn|Brunzel|2018|pp=161–2}} Crystals can also appear as poorly defined aggregates of granular material, termed amorphous urates or amorphous phosphates (urates form in acid urine while phosphates form in alkaline urine). These are of no clinical significance, but they can interfere with microscopy by obscuring other elements (especially bacteria).{{sfn|Haber et al.|2010|p=234–5}} Some drugs, such as [[sulfonamides]], may form crystals when excreted in the urine, and ammonium biurate crystals commonly occur in aged samples.{{sfn|Brunzel|2018|pp=161–2}}

The presence of crystals in the urine has conventionally been associated with the formation of [[kidney stones]], and crystalluria is more common in people with kidney stones than those without. However, crystalluria occurs in up to 20% of the normal population, so it is not a reliable diagnostic marker.<ref name="frochot">{{cite journal|last1=Frochot|first1=V.|last2=Daudon|first2=M.|title=Clinical value of crystalluria and quantitative morphoconstitutional analysis of urinary calculi|journal=[[International Journal of Surgery]]|volume=36 (Pt D)|pages=624–632|doi=10.1016/j.ijsu.2016.11.023|date=2016|issue=Pt D |pmid=27847293 }}</ref> Some types of crystals are characteristically associated with disease states. [[Leucine]] and [[tyrosine]] crystals may be observed in liver disease,<ref name="echeverry">{{cite book|last1=Echeverry|first1=G.|last2=Hortin|first2=G.L.|last3=Rai|first3=A.J.|title=The Urinary Proteome |chapter=Introduction to Urinalysis: Historical Perspectives and Clinical Application |series=[[Methods in Molecular Biology]]|date=2010|volume=641|pages=1–12|doi=10.1007/978-1-60761-711-2_1|pmid=20407938 |isbn=978-1-60761-710-5 }}</ref> and [[cystine]] crystals indicate [[cystinuria]] (although they look identical to hexagonal variants of uric acid crystals, and can only be distinguished with further testing).{{sfn|Haber et al.|2010|p=290}} [[Cholesterol]] crystals may rarely be seen in [[nephrotic syndrome]] and [[chyluria]].{{sfn|Haber et al.|2010|p=299}}

===Organisms===
[[Image:Bacteriuria pyuria 4.jpg|thumb|left|[[Phase-contrast microscopy|Phase-contrast microscopic]] image showing many bacteria and white blood cells in the urine. These changes suggest a urinary tract infection.]]
Microorganisms that can be observed in the urine include bacteria, [[yeast]] and ''[[Trichomonas vaginalis]]''.{{sfn|McPherson|Pincus|2017|p=472}} The urine of children with [[pinworm]] infections may contain ''[[Enterobius vermicularis]]'' eggs, and ''[[Schistosoma haematobium]]'' ova  may be detected in urine samples from individuals with parasitic infestations.{{sfn|Brunzel|2018|p=176}}

===Other elements===
[[Mucus]] can occur in the urine, where it appears as translucent wavy strands under the microscope. The presence of mucus is not a clinically significant finding, but it can be confused with hyaline casts. [[Sperm]] may occasionally be observed in the urine of both males and females; in female children and vulnerable adults, this can indicate [[sexual abuse]]. Reporting the presence of sperm in human urine (spermaturia), especially in women,is a controversial topic.<ref>{{cite web |last1=Novak |first1=Robert |title=Q. Are there any recommendations about reporting sperm on a microscopic urine examination? Some of our technologists have been trained to not report them, and some report them only on men. |url=https://www.captodayonline.com/Archives/q_and_a/qa_0501.html |publisher=CAP Today |access-date=24 February 2024 |date=May 2001}}</ref><ref>{{cite news |last1=Kiechle MD, PhD |first1=Fredrick |title=Q&A - What is the standard for reporting sperm in urine? |url=https://www.captodayonline.com/Archives/1109/1109_qa.html |access-date=24 February 2024 |publisher=CAP Today |date=Nov 2009}}</ref><ref>{{cite journal |title=Answering your questions on HEW certification vs. BS degrees, reporting spermatozoa in urine exams, Calcoflour stains, and hair analysis. |journal=Medical Laboratory Observer |date=Dec 1, 1997 |url=https://www.thefreelibrary.com/Answering+your+questions+on+HEW+certification+vs.+BS+degrees%2C...-a020250658|first1=Daniel|last1=Baer}}</ref> [[Fat]] droplets and [[oval fat bodies]] may be present in a condition called [[lipiduria]], which has various causes, most notably [[nephrotic syndrome]]. Contaminants from the outside environment, such as [[starch]] granules, hair, and clothing fibers, may be seen but are not reported.{{sfn|Brunzel|2018|p=176–80}}

==Interpretation==
{| class="wikitable plainrowheaders mw-collapsible floatright" style="font-size:85%;"
|+ Example of reference values for dipstick urinalysis{{sfn|Turgeon|2016|p=390}}
|-
! scope="col" | Test
! scope="col" | Result
|-
! scope="row" | Blood
|Negative
|-
! scope="row" | Leukocytes
|Negative
|-
! scope="row" | Nitrite
|Negative
|-
! scope="row" | Protein
|Negative to trace
|-
! scope="row" | pH
|5–7
|-
! scope="row" | Specific gravity
|1.003–1.035
|-
! scope="row" | Glucose
|Negative
|-
! scope="row" | Ketones
|Negative
|-
! scope="row" | Bilirubin
|Negative
|-
! scope="row" | Urobilinogen
|<1&nbsp;mg/dL
|-
|}
The interpretation of urinalysis takes into account the results of physical, chemical and microscopic examination and the person's overall condition. Urine test results should always be interpreted using the reference range provided by the laboratory that performed the test, or using information provided by the test strip/device manufacturer.<ref>{{cite web|title=Reference Ranges and What They Mean|url=http://labtestsonline.org/understanding/features/ref-ranges/start/6|publisher=Lab Tests Online (USA)|access-date=22 June 2013|url-status=live|archive-url=https://web.archive.org/web/20130828020717/http://labtestsonline.org/understanding/features/ref-ranges/start/6|archive-date=28 August 2013}}</ref>  Not all abnormal results signify disease, and false positive results are common. For this reason, the use of urinalysis for screening in the general population has been discouraged, but it remains a common practice.{{sfn|Rakel|Rakel|2016|pp=969–70}}

Urinalysis is commonly used to help diagnose urinary tract infections, but the significance of the results depends on the broader clinical situation.{{sfn|Sharp et al.|2020|p=98}} In the setting of UTI symptoms, positive dipstick results for nitrite and leukocyte esterase are strongly suggestive of a UTI,<ref name="chu">{{cite journal|last1=Chu|first1=C.M.|last2=Lowder|first2=J.L.|date=2018|title=Diagnosis and treatment of urinary tract infections across age groups|journal=[[American Journal of Obstetrics and Gynecology]]|volume=219|issue=1|pages=40–51|doi=10.1016/j.ajog.2017.12.231|pmid=29305250 |s2cid=23789220 }}</ref><ref name="dubbs"/> but negative results do not rule it out if there is a high degree of suspicion.<ref name="chu"/><ref name="annals"/> When the dipstick test is positive, microscopy is used to confirm and count WBCs, RBCs and bacteria and assess for possible contamination (signified by a high number of squamous epithelial cells in the sample).<ref name="dubbs">{{citation|last1=Dubbs|first1=S.B.|last2=Sommerkamp|first2=S.K.|date=2019|title=Evaluation and Management of Urinary Tract Infection in the Emergency Department|journal=Emergency Medicine Clinics of North America|volume=37|issue=4|pages=707–723|doi=10.1016/j.emc.2019.07.007|pmid=31563203 |s2cid=201962582 }}</ref> If UTI is suspected, particularly in [[Complicated UTI|complicated cases]] or when urinalysis results are inconclusive,<ref name="annals">{{cite journal|last1=Gupta|first1=K.|last2=Grigoryan|first2=L.|last3=Trautner|first3=B.|date=2017|title=Urinary Tract Infection|journal=[[Annals of Internal Medicine]]|volume=167|issue=7|pages=ITC49–ITC64|doi=10.7326/AITC201710030|pmid=28973215 |s2cid=31963042 }}</ref> a [[urine culture]] may be performed to identify microorganisms if present, obtain a [[colony count]], and carry out [[antibiotic sensitivity testing]]. The colony count helps to distinguish between contamination and infection.{{sfn|Van Leeuwen|Bladh|2019|pp=434–6}}

If a significant quantity of bacteria is present in the urine but there are no symptoms of a UTI, the condition is called [[asymptomatic bacteriuria]]. Asymptomatic bacteriuria is common in elderly people and in those with long-term urinary catheters, and in most cases does not require treatment.<ref name="penfield">{{cite journal|last1=Cortes-Penfield|first1=N.W.|last2=Trautner|first2=B.W.|last3=Jump|first3=R.L.P.|title=Urinary Tract Infection and Asymptomatic Bacteriuria in Older Adults|journal=Infectious Disease Clinics of North America|date=2017|volume=31|issue=4|pages=673–688|doi=10.1016/j.idc.2017.07.002|pmid=29079155 |pmc=5802407 }}</ref> Exceptions include pregnant women, in whom bacteriuria is associated with poorer pregnancy outcomes,<ref name="kalinderi"/> and people undergoing some invasive [[urology]] procedures.<ref name="penfield"/>

A positive dipstick result for blood could signify the presence of red blood cells, hemoglobin, or myoglobin, and therefore requires microscopic analysis for confirmation.{{sfn|Sharp et al.|2020|pp=50–3}} Intact red blood cells will normally be observed under the microscope if present, but they may [[Lysis|lyse]] in dilute or alkaline samples.{{sfn|Brunzel|2018|p=138}} Hemoglobinuria, if unaccompanied by a high quantity of RBCs, can signify [[intravascular hemolysis]] (destruction of red blood cells inside the body).{{sfn|Turgeon|2016|p=403}} [[Myoglobinuria]] occurs in [[rhabdomyolysis]] and other conditions that cause breakdown of muscle tissue.{{sfn|Sharp et al.|2020|pp=57–8}}

If red blood cells are present, the interpretation takes into account whether the urine is visibly bloody (termed [[macroscopic hematuria]]) or if RBCs are only seen on microscopy ([[microscopic hematuria]]).<ref name="peterson"/> Contamination of the sample with blood from a non-urinary source, such as from [[menstruation]] or [[rectal bleeding]], can mimic hematuria,{{sfn|Brunzel|2018|p=139}} and microscopic hematuria is sometimes observed in healthy people after exercise.<ref name="afp2022"/> Other causes of microscopic hematuria include UTI, [[kidney stones]], [[benign prostatic hyperplasia]], and trauma to the urinary tract.<ref name="peterson"/><ref name="nejm">{{cite journal|last=Ingelfinger|first=J.R.|date=2021|title=Hematuria in adults|journal=[[New England Journal of Medicine]]|volume=385|issue=2|pages=153–163|doi=10.1056/NEJMra1604481|pmid=34233098 |s2cid=235768813 }}</ref> Kidney diseases that affect the [[Glomerulus (kidney)|glomerulus]] can cause microscopic hematuria, in which case it is referred to as [[glomerular hematuria]].<ref name="nejm"/> On urine microscopy, the presence of abnormally shaped ("dysmorphic") red blood cells and RBC casts is associated with glomerular hematuria.<ref name="peterson"/>{{sfn|Brunzel|2018|pp=137–8}} Proteinuria and elevated blood [[creatinine]] alongside hematuria suggests kidney dysfunction.<ref name="peterson"/> In people at risk, persistent microscopic hematuria can be a sign of urinary tract cancer and may require further testing, such as urinary tract [[Medical imaging|imaging]] and [[cystoscopy]].<ref name="afp2022"/><ref name="nejm"/> Sometimes no cause can be identified, and the condition is managed with regular monitoring.<ref name="nejm"/> The causes of macroscopic hematuria are similar, but in the absence of an obvious explanation such as trauma or UTI, it is more strongly associated with malignancy and requires further investigation.<ref name="peterson"/>{{sfn|Partin et al.|2021|pp=252–3}}

Elevated levels of protein in the urine are often suggestive of kidney disease, but may have other causes. Proteinuria can occur transiently as a consequence of exercise, fever, stress, or UTI. Proteinuria that occurs only while standing, called [[orthostatic proteinuria]], is relatively common in young men and not associated with disease.{{sfn|Partin et al.|2021|p=18–19}}{{sfn|Sharp et al.|2020|p=82}} In [[multiple myeloma]], [[Bence-Jones protein]] may be secreted into the urine,{{sfn|Rifai|Horvath|Wittwer|2018|p=489}} although this type of proteinuria is not as easily detected by urine dipsticks.<ref name="resimont"/> If proteinuria is persistently detected by dipstick testing, a [[24-hour urine collection]] can be performed to obtain an accurate measurement of protein levels; alternatively, protein excretion can be estimated from the [[urine protein/creatinine ratio]] of a single specimen. Measuring the amount of protein in the urine helps to distinguish between different causes of proteinuria.{{sfn|Partin et al.|2021|p=19}}{{sfn|Sharp et al.|2020|pp=79-80}} [[Urine protein electrophoresis]], which identifies and measures the proportions of different types of protein in the urine, may be used to investigate the cause of proteinuria{{sfn|Partin et al.|2021|p=19}} and to detect Bence-Jones protein.{{sfn|Rifai|Horvath|Wittwer|2018|p=289}} During pregnancy, dipstick testing may be used to screen for proteinuria as it is a sign of [[pre-eclampsia]].<ref name="NICE"/>

==History==
{{multiple image
|total_width=370
|image1=Theophilus Protospatharius.jpg
|alt1=
|image2=Fasciculus_Medicinae_1491.jpg
|alt2=
|footer= Left: [[Theophilus Protospatharius]] holding a blue-gray [[uroscopy]] flask, depicted in a 13th-century manuscript. Right: Urine color wheel from ''[[Fasciculus Medicinae]]'' published by [[Johannes de Ketham]] (1491).
}}
The diagnostic value of urine has been recognized since ancient times. Urine examination was practiced in [[Sumer]] and [[Babylonia]] as early as 4000 BC, and is described in ancient [[Ancient Greek|Greek]] and [[Sanskrit]] texts.<ref name="ki2"/> [[Hippocrates]], [[Celsus]] and [[Galen]] published important works correlating the characteristics of urine with patients' health.{{sfn|Rosenfeld|1999|p=5}} During the [[Middle Ages]] the visual inspection of urine―termed [[uroscopy]]—gained widespread popularity. The 7th-century manuscript ''De Urinis'' by the Byzantine physician [[Theophilus Protospatharius]] is thought to be the earliest publication dedicated solely to the examination of urine. Protospatharius notably described a method for precipitating protein out of urine using heat.<ref name="ki2"/>

Many influential works on urine testing followed. Publications by [[Isaac Judaeus]] built upon Protospatharius' work, and [[Zayn al-Din Gorgani]], an 11th-century Persian physician, published instructions for specimen collection which noted that urine samples were affected by aging and exposure to heat and light. Other medieval writers included [[Gilles de Corbeil]], who published a popular [[mnemonic]] poem on uroscopy and introduced the [[Uroscopy#Matula (flask)|matula]], a round flask used to examine urine; and [[Joannes Actuarius]], who wrote a series of books on uroscopy in seven volumes. The 1491 book ''[[Fasciculus Medicinae]]'', published by [[Johannes de Ketham]], became popular with laypeople and was used for self-diagnosis.<ref name="ki2">{{cite journal|last=Armstrong|first=J.A.|title=Urinalysis in Western culture: a brief history|journal= Kidney International|date=2007|volume=71|issue=5|pages=384–7|doi=10.1038/sj.ki.5002057|pmid=17191081 |doi-access=free}}</ref><ref name="kamaledeen">{{cite journal|last1=Kamaledeen|first1=A.|last2=Vivekanantham|first2=S.|title=The rise and fall of uroscopy as a parable for the modern physician|journal=Journal of the Royal College of Physicians of Edinburgh|date=2015|volume=45|issue=1|pages=63–6|doi=10.4997/JRCPE.2015.115|pmid=25874834 |doi-access=free}}</ref> The matula came to symbolize the practice of medicine in general.{{sfn|Rosenfeld|1999|pp=6–9}}
{{multiple image
|align=left
|total_width=370
|image1=A physician examining a urine-flask brought by a woman. Oil Wellcome M0013918.jpg
|alt1=
|image2=Hogarth%27s_The_Company_of_Undertakers._Wellcome_M0011548.jpg
|alt2=
|footer=Left: A physician examining a urine-flask brought by a woman; oil painting after [[Caspar Netscher]] (1639–1684). Right: ''[[The Company of Undertakers]]'', a satirical 1736 engraving by [[William Hogarth]] depicting various forms of [[quackery]]. A man holding a urine flask appears in the lower right.}}
Physicians of antiquity interpreted the color of urine using circular charts listing correspondences with disease states. The relation of urine characteristics to disease was based on the theory of the [[four humors]].{{sfn|Rosenfeld|1999|pp=6–9}} Different areas of the matula flask were thought to represent different organs and regions of the human body.<ref name="acjk">{{cite journal|last=Eknoyan|first=G.|date=2007|title=Looking at the urine: the renaissance of an unbroken tradition. |journal=[[American Journal of Kidney Diseases]]|volume=49|issue=6|pages=865–872|doi=10.1053/j.ajkd.2007.04.003|pmid=17533032 |doi-access=free}}</ref> In the 16th century, [[Paracelsus]] applied the principles of [[alchemy]] to the study of urine.{{sfn|Haber et al.|2010|p=10}} He believed that materials obtained from distillation and precipitation of the urine could provide diagnostic information. In this respect he could be regarded as a progenitor of biochemical methods for urinalysis.{{sfn|Rosenfeld|1999|pp=4–7}}

During the late Middle Ages and the [[Renaissance]], the abuse of uroscopy by disreputable individuals began to draw criticism. "Uromancers" without medical training claimed that they could not only diagnose disease, but detect pregnancy, determine a baby's sex, and even predict the future from a subject's urine. In 1637 the English physician [[Thomas Brian]] published ''The Pisse-Prophet, or, Certaine Pisse-Pot Lectures'', excoriating those who claimed to be able to diagnose diseases by uroscopy without examining the patient.{{sfn|Rosenfeld|1999|pp=9–10}}<ref name="clinmed">{{cite journal|last=Connor|first=H.|date=2001|title=Medieval uroscopy and its representation on misericords--part 1: Uroscopy|journal=Clinical Medicine|volume=1|issue=6|pages=507–509|doi=10.7861/clinmedicine.1-6-507|pmid=11792095 |pmc=4953881 }}</ref>

The 19th century saw a proliferation in chemical methods for the analysis of urine, but these techniques were labor-intensive and impractical; in one contemporary editorial a physician complained about the dangers of keeping [[nitric acid]] (used to detect albumin) in one's pocket.<ref name="voswinckel"/><ref name="gazette">{{cite journal|title=Editorial: Tests for albumen in urine|journal=[[Medical Times and Gazette]]|volume=2|pages=365–366|date=1874|url=https://books.google.com/books?id=6JUEAAAAQAAJ&pg=PA366}}</ref> A search for more convenient techniques ensued. An early method resembling urine test strips was devised by the French chemist {{ill|Edme-Jules Maumené|fr}} in 1850. Maumené impregnated a strip of wool with [[tin(II) chloride]], added a drop of urine, and exposed it to a flame. If the urine contained glucose, the wool would turn black. In the 1880s [[William Pavy]] developed powdered reagents for urinalysis, and [[George Oliver (physician)|George Oliver]] introduced "Urinary Test Papers" for albumin and glucose, which were a commercial success and were marketed in Germany as well as the United Kingdom.<ref name="voswinckel"/><ref name="si">{{cite journal|last1=Cameron|first1=S.|last2=Neild|first2=G.H.|date=2013|title=Oliver and Feigl: 2 forgotten fathers of "stick" testing of urine for albumin|journal=[[Journal of Nephrology]]|volume=26|issue=Suppl. 22|pages=77–81|doi=10.5301/jn.5000344|doi-broken-date=1 November 2024 |pmid=24375346 }}</ref> From 1900 onwards there was a proliferation of commercial reagent kits for urinalysis.<ref name="voswinckel">{{cite journal|last=Voswinckel|first=P.|date=1994|title=A marvel of colors and ingredients. The story of urine test strips|journal=Kidney International|volume=Suppl. 47|pages=S3–S7|pmid=7869669|url=https://archive.org/details/sim_kidney-international_1994-11_46_supplement-47/page/n11/mode/2up}}</ref>  Beginning in the 1920s, the chemist [[Fritz Feigl]] developed highly sensitive methods for [[spot test]]ing on filter paper, which paved the way for modern urine test strips. Feigl also introduced the method of protein detection using the protein error of indicators, which is still used today.<ref name="voswinckel"/><ref name="si"/>

In 1956 [[Helen Murray Free]] and her husband developed Clinistix (also known as [[Clinistrip]]), the first dip-and-read test for glucose in urine for patients with diabetes.<ref>{{cite web|title=Helen M. Free|url=https://www.acs.org/content/acs/en/education/whatischemistry/women-scientists/helen-m-free.html|website=American Chemical Society|access-date=13 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161113115210/https://www.acs.org/content/acs/en/education/whatischemistry/women-scientists/helen-m-free.html|archive-date=13 November 2016}}</ref> This breakthrough led to additional dip-and-read tests for other substances.<ref>{{cite web|title=The Development of Diagnostic Test Strips|url=https://www.acs.org/content/dam/acsorg/education/whatischemistry/landmarks/diagnosticteststrips/development-of-diagnostic-test-strips-commemorative-booklet.pdf|website=American Chemical Society|access-date=13 November 2016|url-status=live|archive-url=https://web.archive.org/web/20170207064437/https://www.acs.org/content/dam/acsorg/education/whatischemistry/landmarks/diagnosticteststrips/development-of-diagnostic-test-strips-commemorative-booklet.pdf|archive-date=7 February 2017}}</ref> The invention was named a National Historic Chemical Landmark by the American Chemical Society in May 2010.<ref>{{cite web|title=Al and Helen Free and the development of diagnostic test strips|url=https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/diagnosticteststrips.html|website=American Chemical Society|access-date=13 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161113120018/https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/diagnosticteststrips.html|archive-date=13 November 2016}}</ref> A dipstick test for urine protein, called Albustix, was introduced by [[Miles Laboratories]] in 1957,{{sfn|Rosenfeld|1999|p=148}} and the first multi-test dipsticks were released in 1959. Automated test strip readers came onto the market in the 1980s.{{sfn|Rosenfeld|1999|p=327}}

==See also==
{{col div|colwidth=30em}}
* [[Uroscopy]], the ancient form of this analysis
* [[Urinary casts]]
* [[Proteinuria]]
* [[Urine test strip]]
* [[Urine collection device]]
* [[Pregnancy test]], measures [[Human chorionic gonadotropin|hCG]] levels in urine
{{colend}}

==References==
{{reflist|33em}}

==Works cited==
{{refbegin|30em}}
*{{cite book|last1= Bain|first1=B.J.|title=Blood Cells: A Practical Guide|url=https://books.google.com/books?id=dckoCQAAQBAJ|year=2015|publisher=[[John Wiley & Sons]]|isbn=978-1-118-81733-9|edition=5}}
*{{cite book|title=Fundamentals of Urine and Body Fluid Analysis|last=Brunzel|first=N.A.|date=2018|publisher=[[Elsevier]]|edition=4|isbn=978-0-323-37479-8|url=https://books.google.com/books?id=_D5yDQAAQBAJ}}
*{{cite book|title=Color Atlas of the Urinary Sediment: An Illustrated Field Guide Based on Proficiency Testing|last1=Haber|first1=M.H.|last2=Blomberg|first2=D.|last3=Galagan|first3=K.|last4=Glassy|first4=E.F.|last5=Ward|first5=P.C.J.|publisher=[[College of American Pathologists]]|date=2010|isbn=978-0-930304-87-4|ref={{harvid|Haber et al.|2010}}}} <!-- use {{sfn|Haber et al.|2010}} to cite this -->
*{{cite book |last1=Hoffman |first1=Karl Berthold |last2=Ultzmann |first2=Robert |title=Analysis of the urine |date=1886 |publisher=D. Appleton and company |location=New York |lccn=07000368}}
*{{cite book|last1=McPherson|first1=R.A.|last2=Pincus|first2=M.R.|title=Henry's Clinical Diagnosis and Management by Laboratory Methods|url=https://books.google.com/books?id=xAzhCwAAQBAJ|year=2017|publisher=Elsevier Health Sciences|isbn=978-0-323-41315-2|edition=23}}
*{{cite book|title=Graff's Textbook of Urinalysis and Body Fluids|edition=3|last1=Mundt|first1=L.A.|last2=Shanahan|first2=K.|date=2016|isbn=978-1-4963-2016-2|publisher=[[Wolters Kluwer]]}} 
*{{cite book|title=Netter's Essential Histology|edition=3|last1=Ovalle|first1=W.K.|last2=Nahirney|first2=P.|date=2021|isbn=978-0-323-69464-3|publisher=Elsevier|url=https://books.google.com/books?id=StnNDwAAQBAJ}}
*{{cite book|title=Campbell-Walsh-Wein Urology|last1=Partin|first1=A.W.|last2=Dmochowski|first2=R.R.|last3=Kavoussi|first3=L.R.|last4=Peters|first4=C.A.|date=2021|publisher=Elsevier|isbn=978-0-323-54642-3|url=https://books.google.com/books?id=RdfLDwAAQBAJ|ref={{harvid|Partin et al.|2021}} }}
*{{cite book|title=Textbook of Family Medicine|last1=Rakel|first1=R.E.|last2=Rakel|first2=D.P.|date=2016|publisher=Elsevier|isbn=978-0-323-23990-5|edition=9|url=https://books.google.com/books?id=8huMBgAAQBAJ}}
*{{cite book|title=Tietz Textbook of Clinical Chemistry and Molecular Diagnostics|last1=Rifai|first1=N.|last2=Horvath|first2=A.R.|last3=Wittwer|first3=C.T.|edition=6|publisher=Elsevier|date=2018|isbn=978-0-323-35921-4|url=https://books.google.com/books?id=3mRgDwAAQBAJ}}
*{{cite book|last=Rosenfeld|first=L.|title=Four Centuries of Clinical Chemistry|date=1999|publisher=[[Taylor & Francis]]|isbn=90-5699-645-2}}
*{{cite book|last1=Sharp|first1=V.J.A.|last2=Antes|first2=L.M.|last3=Sanders|first3=M.L.|last4=Lockwood|first4=G.M.|date=2020|title=Urine Tests: A Case-Based Guide to Clinical Evaluation and Application|url=https://books.google.com/books?id=divyDwAAQBAJ|publisher=[[Springer (publisher)|Springer]]|isbn=978-3-030-29138-9|ref={{harvid|Sharp et al.|2020}}}}
*{{cite book|last=Turgeon|first=M.L.|title=Linné & Ringsrud's Clinical Laboratory Science: Concepts, Procedures, and Clinical Applications|url=https://books.google.com/books?id=QyvRoQEACAAJ|year=2016|publisher=Elsevier Mosby|isbn=978-0-323-22545-8|edition=7}}
* {{cite book|last1=Walls|first1=R.|last2=Hockberger|first2=R.|last3=Gausche-Hill|first3=M.|title=Rosen's Emergency Medicine - Concepts and Clinical Practice|url=https://books.google.com/books?id=OANODgAAQBAJ|edition=9|year=2017|publisher=Elsevier Health Sciences|isbn=978-0-323-39016-3}}
* {{cite book|last1=Van Leeuwen|first1=A.M.|last2=Bladh|first2=M.L.|title=Davis's Comprehensive Manual of Laboratory and Diagnostic Tests with Nursing Implications|url=https://books.google.com/books?id=cpWNDwAAQBAJ|year=2019|publisher=F. A. Davis Company|isbn=978-0-8036-9448-4|edition=8}}
{{refend}}

==External links==
{{Commons category|Urinalysis}}
* [http://digital2.library.ucla.edu/viewItem.do?ark=21198/zz0002267k Conoximent de las Orines, an early book about analyzing urine for medical purposes. Estimated date 1466.]

{{Abnormal clinical and laboratory findings for urine|state=expanded}}

[[Category:Diagnostic nephrology]]
[[Category:Urine tests| ]]