Editing Kidney stone disease (section)

== Diagnosis ==
Diagnosis of kidney stones is made on the basis of information obtained from the history, physical examination, [[urinalysis]], and [[radiography|radiographic]] studies.<ref name=Anoia2009 /> [[Medical diagnosis|Clinical diagnosis]] is usually made on the basis of the location and severity of the pain, which is typically colicky in nature (comes and goes in [[spasm]]odic  waves). Pain in the back occurs when calculi produce an obstruction in the kidney.<ref name=Weaver2002 /> Physical examination may reveal fever and [[Murphy's punch sign|tenderness at the costovertebral angle]] on the affected side.<ref name=Anoia2009 />

=== Imaging studies ===
Calcium-containing stones are relatively [[Radiodensity|radiodense]] (opaque to [[X-ray]]s), and they can often be detected by a traditional [[radiography]] of the [[abdomen]] that includes the [[kidneys, ureters, and bladder x-ray|kidneys, ureters, and bladder]] (KUB film{{Clarify|date=February 2024}}).<ref name=Pietrow2006 /> KUB{{Clarify|date=February 2024}} radiography, although useful in monitoring size of stone or passage of stone in stone formers, might not be useful in the acute setting due to low sensitivity.<ref>{{cite journal |last1=Brisbane |first1=Wayne |last2=Bailey |first2=Michael R. |last3=Sorensen |first3=Mathew D. |date=November 2016 |title=An overview of kidney stone imaging techniques |journal=Nature Reviews. Urology |volume=13 |issue=11 |pages=654–662 |doi=10.1038/nrurol.2016.154 |issn=1759-4812 |pmc=5443345 |pmid=27578040}}</ref> Some 60% of all renal stones are radiopaque.<ref name=SmithCentennial2000 /><ref name=Bushinsky2007 /> In general, calcium phosphate stones have the greatest density, followed by calcium oxalate and magnesium ammonium phosphate stones. [[Cystine]] calculi are only faintly [[radiodense]], while [[uric acid]] stones are usually entirely [[radiolucent]].<ref name=Smith1999 />

In people with a history of stones, those who are less than 50 years of age and are presenting with the symptoms of stones without any concerning signs do not require [[Helical cone beam computed tomography|helical CT scan]] imaging.<ref>{{cite web|author1=American College of Emergency Physicians|title=Ten Things Physicians and Patients Should Question|url=http://www.choosingwisely.org/doctor-patient-lists/american-college-of-emergency-physicians/|website=Choosing Wisely|access-date=14 January 2015|date=27 October 2014|url-status=live|archive-url=https://web.archive.org/web/20140307012443/http://www.choosingwisely.org/doctor-patient-lists/american-college-of-emergency-physicians/|archive-date=7 March 2014|df=dmy-all}}</ref> A [[CT scan|computed tomography]] (CT) scan is also not typically recommended in children.<ref>{{cite web|title=American Urological Association {{!}} Choosing Wisely|url=http://www.choosingwisely.org/societies/american-urological-association/|website=www.choosingwisely.org|access-date=28 May 2017|url-status=dead|archive-url=https://web.archive.org/web/20170223133729/http://www.choosingwisely.org/societies/american-urological-association/|archive-date=23 February 2017|df=dmy-all}}</ref>

Otherwise a noncontrast helical CT scan with {{convert|5|mm|in|1|sp=us}} sections is the diagnostic method to use to detect kidney stones and confirm the diagnosis of kidney stone disease.<ref name=Pearle2007 /><ref name=Anoia2009 /><ref name=SmithCentennial2000 /><ref name=Fang2009 /><ref name=Miller2007 /> Near all stones are detectable on CT scans with the exception of those composed of certain drug residues in the urine,<ref name=Pietrow2006 /> such as from [[indinavir]].

Where a CT scan is unavailable, an [[intravenous pyelogram]] may be performed to help confirm the diagnosis of [[urolithiasis]]. This involves [[Intravenous therapy|intravenous injection]] of a [[Radiocontrast|contrast agent]] followed by a KUB film. [[Urolith]]s present in the kidneys, ureters, or bladder may be better defined by the use of this contrast agent. Stones can also be detected by a [[retrograde pyelogram]], where a similar contrast agent is injected directly into the distal ostium of the ureter (where the ureter terminates as it enters the bladder).<ref name=SmithCentennial2000 />

[[Renal ultrasonography]] can sometimes be useful, because it gives details about the presence of [[hydronephrosis]], suggesting that the stone is blocking the outflow of urine.<ref name=Pietrow2006 /> Radiolucent stones, which do not appear on KUB, may show up on ultrasound imaging studies. Other advantages of renal ultrasonography include its low cost and absence of [[Radiology|radiation exposure]]. Ultrasound imaging is useful for detecting stones in situations where X-rays or CT scans are discouraged, such as in children or pregnant women.<ref name="semins">{{cite journal | vauthors = Semins MJ, Matlaga BR | title = Management of urolithiasis in pregnancy | journal = International Journal of Women's Health | volume = 5 | pages = 599–604 | date = September 2013 | pmid = 24109196 | pmc = 3792830 | doi = 10.2147/ijwh.s51416 | doi-access = free }}</ref> Despite these advantages, renal ultrasonography in 2009 was not considered a substitute for noncontrast helical CT scan in the initial diagnostic evaluation of urolithiasis.<ref name=Fang2009 /> The main reason for this is that, compared with CT, renal ultrasonography more often fails to detect small stones (especially ureteral stones) and other serious disorders that could be causing the symptoms.<ref name=Cutler2007 />

On the contrary, a 2014 study suggested that ultrasonography should be used as the initial diagnostic imaging test, with further imaging studies be performed at the discretion of the physician on the basis of clinical judgment, and using [[ultrasonography]] rather than [[CT scan|CT]] as an initial diagnostic test results in less radiation exposure and equally good outcome.<ref>{{cite journal | vauthors = Smith-Bindman R, Aubin C, Bailitz J, Bengiamin RN, Camargo CA, Corbo J, Dean AJ, Goldstein RB, Griffey RT, Jay GD, Kang TL, Kriesel DR, Ma OJ, Mallin M, Manson W, Melnikow J, Miglioretti DL, Miller SK, Mills LD, Miner JR, Moghadassi M, Noble VE, Press GM, Stoller ML, Valencia VE, Wang J, Wang RC, Cummings SR | title = Ultrasonography versus computed tomography for suspected nephrolithiasis | journal = The New England Journal of Medicine | volume = 371 | issue = 12 | pages = 1100–10 | date = September 2014 | pmid = 25229916 | doi = 10.1056/NEJMoa1404446 | s2cid = 4511678 | url = https://escholarship.org/content/qt1cm5f8cd/qt1cm5f8cd.pdf?t=nwl44w | access-date = 25 September 2019 | archive-date = 14 March 2020 | archive-url = https://web.archive.org/web/20200314051953/https://escholarship.org/content/qt1cm5f8cd/qt1cm5f8cd.pdf?t=nwl44w | url-status = live }}</ref>

<gallery>
File:Kidney stones abdominal X-ray.jpg|Bilateral kidney stones can be seen on this [[Kidneys, ureters, and bladder x-ray|KUB radiograph]]. There are [[phlebolith]]s in the pelvis, which can be misinterpreted as [[bladder stone]]s.
File:3mmstone.png|[[Transverse plane|Axial]] [[X-ray computed tomography|CT scan]] of abdomen without contrast, showing a 3-mm stone (marked by an arrow) in the left proximal [[ureter]]
File:Ultrasonography of renal stone located at the pyeloureteric junction.jpg|[[Renal ultrasonograph]] of a stone located at the pyeloureteric junction with accompanying hydronephrosis.
File:CT measurement of kidney stone in soft tissue and bone window.jpg|Measurement of a 5.6&nbsp;mm large kidney stone in soft tissue versus skeletal [[CT scan#Process|CT window]].
</gallery>

=== Laboratory examination ===
[[File:Struvite crystals dog with scale 1.JPG|thumb|[[Struvite]] crystals found on [[Urine microscopy|microscopic examination]] of the urine]]

Laboratory investigations typically carried out include:<ref name=Anoia2009 /><ref name=Fang2009 /><ref name=Pietrow2006 /><ref name=NIDDK2007 />
* [[Urine microscopy|microscopic examination]] of the urine, which may show [[red blood cell]]s, bacteria, [[leukocyte]]s, [[urinary cast]]s, and crystals;
* urine culture to identify any infecting organisms present in the urinary tract and [[Kirby-Bauer antibiotic testing|sensitivity]] to determine the susceptibility of these organisms to specific antibiotics;
* [[complete blood count]], looking for [[neutrophilia]] (increased [[neutrophil granulocyte]] count) suggestive of bacterial infection, as seen in the setting of struvite stones;
* [[renal function]] tests to look for abnormally high blood calcium levels ([[Hypercalcaemia|hypercalcemia]]);
* 24&nbsp;hour urine collection to measure total daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate, and [[phosphate]];
* collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple [[tea strainer]]) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.
{{clear}}

=== Composition ===

{| class="wikitable"
|- style="line-height:133%"
! Kidney<br>stone<br>type
! Relative<br>incidence<br>(adults)<ref name=Frassetto2011>{{cite journal | author= Frassetto L, Kohlstadt I | title= Treatment and prevention of kidney stones: an update. | journal= Am Fam Physician | year= 2011 | volume= 84 | issue= 11 | pages= 1234–42 | pmid= 22150656 | doi=  | pmc=  | url= https://pubmed.ncbi.nlm.nih.gov/22150656 | archive-date= 22 September 2023 | access-date= 28 August 2023 | archive-url= https://web.archive.org/web/20230922163226/https://pubmed.ncbi.nlm.nih.gov/22150656/ | url-status= live }}<br>Including cystine stone incidence of 1%</ref>
! Circumstances
! Color and<br>microscopy<br>appearance
! Radio-density
! Details
|-
| [[Calcium oxalate|Calcium<br>oxalate]]
| 60%
| when urine is acidic (decreased pH)<ref>{{cite book| vauthors = Becker KL |title=Principles and practice of endocrinology and metabolism|date=2001|publisher=Lippincott, Williams & Wilkins|location=Philadelphia, Pa. [u.a.]|isbn=978-0-7817-1750-2|page=684|edition=3|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA684|url-status=live|archive-url=https://web.archive.org/web/20170908221053/https://books.google.com/books?id=FVfzRvaucq8C&pg=PA684|archive-date=8 September 2017|df=dmy-all}}</ref>
| Black/dark brown [[File:Calcium oxalate crystal.jpg|center|70 px]]
| Radio-opaque
| Some of the oxalate in urine is produced by the body. Calcium and oxalate in the diet play a part but are not the only factors that affect the formation of calcium oxalate stones. Dietary oxalate is found in many vegetables, fruits, and nuts. Calcium from bone may also play a role in kidney stone formation.
|-
| [[Calcium phosphate|Calcium<br>phosphate]]
| 10–20%
| when urine is alkaline (high pH)
| Dirty white [[File:Calcium phosphate crystal.jpg|center|70 px]]
| Radio-opaque
| Tends to grow in alkaline urine especially when [[Proteus (bacterium)|''Proteus'' bacteria]] are present. The most common type among pregnant women.<ref name=Frassetto2011/>
|-
| [[Uric acid]]
| 10–20%
| when urine is persistently acidic
| Yellow/reddish brown [[File:Uric acid crystal.jpg|center|70 px]]
| Radio-lucent
| Diets rich in animal proteins and purines: substances found naturally in all food but especially in organ meats, fish, and shellfish.
|-
| [[Struvite]]
| {{0}}3%
| infections in the kidney and when urine is alkaline (high pH)
| Dirty white [[File:Struvite crystals.jpg|center|70 px]]
| Radio-opaque
| Prevention of struvite stones depends on staying infection-free. Diet has not been shown to affect struvite stone formation.
|-
| [[Cystine]]
| {{0}}1–2%<ref>{{cite web|title=Cystine stones|url=http://www.uptodate.com/contents/cystine-stones|work=[[UpToDate]]|access-date=20 February 2014|url-status=live|archive-url=https://web.archive.org/web/20140226110022/http://www.uptodate.com/contents/cystine-stones|archive-date=26 February 2014|df=dmy-all}}</ref>
| rare genetic disorder
| Pink/yellow [[File:Cystine crystals.jpg|center|70 px]]
| Radio-opaque
| Cystine, an amino acid (a dimer of cysteine, of the building blocks of protein), leaks through the kidneys and into the urine to form crystals.
|-
| [[Xanthine]]<ref>Bailey & Love's/25th/1296</ref>
|
| extremely rare
| Brick red
| Radio-lucent
|
|}

[[File:Surface of a kidney stone.jpg|thumb|Scanning electron micrograph of the surface of a kidney stone showing tetragonal crystals of [[weddellite]] (calcium oxalate dihydrate) emerging from the amorphous central part of the stone (the horizontal length of the picture represents 0.5 mm of the figured original)]]
[[File:Kidney stones, Uric acid.JPG|thumb|Multiple kidney stones composed of [[uric acid]] and a small amount of [[calcium oxalate]]]]
[[File:Lenticular kidney stone.jpg|thumb|A lenticular kidney stone, excreted in the urine]]

==== Calcium-containing stones ====
By far, the most common type of kidney stones worldwide contains calcium. For example, calcium-containing stones represent about 80% of all cases in the United States; these typically contain [[calcium oxalate]] either alone or in combination with [[calcium phosphate]] in the form of [[apatite]] or [[brushite]].<ref name=Reilly2005Ch13 /><ref name=Coe2005 /> Factors that promote the [[Precipitation (chemistry)|precipitation]] of oxalate crystals in the urine, such as [[primary hyperoxaluria]], are associated with the development of calcium oxalate stones.<ref name=Hoppe2003 /> The formation of calcium phosphate stones is associated with conditions such as [[hyperparathyroidism]]<ref name=NIDDK2006 /> and [[renal tubular acidosis]].<ref name=NIDDK20084696 />

[[Oxaluria]] is increased in patients with certain gastrointestinal disorders including inflammatory bowel disease such as [[Crohn's disease]] or in patients who have undergone resection of the small bowel or small-bowel bypass procedures. Oxaluria is also increased in patients who consume increased amounts of oxalate (found in vegetables and nuts). Primary hyperoxaluria is a rare autosomal recessive condition that usually presents in childhood.<ref name="De Mais">{{cite book | vauthors = De Mais D |title= ASCP Quick Compendium of Clinical Pathology |edition= 2nd |publisher= ASCP Press |location= Chicago |year= 2009 }}</ref>

Calcium oxalate crystals can come in two varieties. Calcium oxalate monohydrate can appear as 'dumbbells' or as long ovals that resemble the individual posts in a picket fence. Calcium oxalate dihydrate have a tetragonal "envelope" appearance.<ref name="De Mais" />

==== Struvite stones ====
About 10–15% of urinary calculi are composed of [[struvite]] (hexa-hydrated [[ammonium magnesium phosphate]], NH<sub>4</sub>MgPO<sub>4</sub>·6H<sub>2</sub>O).<ref name=Heptinstall2007 /> Struvite stones (also known as "infection stones," [[urease]], or triple-phosphate stones) form most often in the presence of infection by urea-splitting [[bacteria]]. Using the enzyme urease, these organisms [[Metabolism|metabolize]] [[urea]] into [[ammonia]] and [[carbon dioxide]]. This [[alkalinity|alkalinizes]] the urine, resulting in favorable conditions for the formation of struvite stones. ''[[Proteus mirabilis]]'', ''[[Proteus vulgaris]]'', and ''[[Morganella morganii]]'' are the most common organisms isolated; less common organisms include ''[[Ureaplasma urealyticum]]'' and some species of ''[[Providencia (bacterium)|Providencia]]'', ''[[Klebsiella]]'', ''[[Serratia]]'', and ''[[Enterobacter]]''. These infection stones are commonly observed in people who have factors that predispose them to [[urinary tract infection]]s, such as those with [[spinal cord injury]] and other forms of [[neurogenic bladder]], [[ileal conduit urinary diversion]], [[vesicoureteral reflux]], and [[Obstructive uropathy|obstructive uropathies]]. They are also commonly seen in people with underlying metabolic disorders, such as [[idiopathic]] [[hypercalciuria]], [[hyperparathyroidism]], and [[gout]]. Infection stones can grow rapidly, forming large calyceal staghorn ([[antler]]-shaped) calculi requiring invasive surgery such as percutaneous nephrolithotomy for definitive treatment.<ref name=Heptinstall2007 />

Struvite stones (triple-phosphate/magnesium ammonium phosphate) have a 'coffin lid' morphology by microscopy.<ref name="De Mais" />

==== Uric acid stones ====
About 5–10% of all stones are formed from [[uric acid]].<ref name=Moe2006 /> People with certain metabolic abnormalities, including [[obesity]],<ref name=Johri2010 /> may produce uric acid stones. They also may form in association with conditions that cause [[hyperuricosuria]] (an excessive amount of uric acid in the urine) with or without [[hyperuricemia]] (an excessive amount of uric acid in the [[blood serum|serum]]). They may also form in association with disorders of acid/base metabolism where the urine is excessively acidic (low [[pH]]), resulting in precipitation of uric acid crystals. A diagnosis of uric acid [[urolithiasis]] is supported by the presence of a [[Radiodensity|radiolucent]] stone in the face of persistent urine acidity, in conjunction with the finding of uric acid crystals in fresh urine samples.<ref name=Halabe1994 />

As noted above (section on calcium oxalate stones), people with [[inflammatory bowel disease]] ([[Crohn's disease]], [[ulcerative colitis]]) tend to have [[hyperoxaluria]] and form oxalate stones. They also have a tendency to form urate stones. Urate stones are especially common after [[Colectomy|colon resection]].

Uric acid stones appear as [[Pleomorphism (cytology)|pleomorphic]] crystals, usually diamond-shaped.  They may also look like squares or rods which are polarizable.<ref name="De Mais" />

==== Other types ====
[[File:Cystine Crystals in Canine Urine Sediment.jpg|alt=Translucent, hexagon-shaped crystals seen through a microscope|thumb|Microscopic [[cystine]] crystals have a distinctive hexagonal shape and are present in the urine of people with kidney stones composed of cystine]]
People with certain rare [[Inborn error of metabolism|inborn errors of metabolism]] have a propensity to accumulate crystal-forming substances in their urine. For example, those with [[cystinuria]], [[cystinosis]], and [[Fanconi syndrome]] may form stones composed of [[cystine]]. Cystine stone formation can be treated with urine alkalinization and dietary protein restriction.  People affected by [[xanthinuria]] often produce stones composed of [[xanthine]]. People affected by [[adenine phosphoribosyltransferase deficiency]] may produce [[2,8-dihydroxyadenine]] stones,<ref name=Kamatani1996 /> [[Alkaptonuria|alkaptonurics]] produce [[homogentisic acid]] stones, and [[Iminoglycinuria|iminoglycinurics]] produce stones of [[glycine]], [[proline]], and [[hydroxyproline]].<ref name=Rosenberg1968 /><ref name=Coskun1993 /> Urolithiasis has also been noted to occur in the setting of therapeutic drug use, with crystals of drug forming within the renal tract in some people currently being treated with agents such as [[indinavir]],<ref name=Crixivan2010 /> [[sulfadiazine]],<ref name=Schlossberg2011 /> and [[triamterene]].<ref name=Carr1990 />

=== Location ===
[[File:Blausen 0595 KidneyStones.png|thumb|Illustration of kidney stones]]

Urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder.<ref name=Pearle2007 /> Nephrolithiasis refers to the presence of such stones in the kidneys. Calyceal calculi are aggregations in either the [[minor calyx|minor]] or [[major calyx]], parts of the kidney that pass urine into the ureter (the tube connecting the kidneys to the urinary bladder). The condition is called ureterolithiasis when a calculus is located in the ureter. Stones may also form or pass into the bladder, a condition referred to as [[bladder stone]]s.<ref name=McNutt1893 />

===Size===
[[File:Staghorn Kidney Stone 08779.jpg|thumb|Radiograph showing a large staghorn calculus involving the [[major calyx|major calyces]] and [[renal pelvis]] in a person with severe [[scoliosis]]]]
Stones less than {{convert|5|mm|in|1|abbr=on}} in diameter pass spontaneously in up to 98% of cases, while those measuring {{convert|5|to|10|mm|in|1|abbr=on}} in diameter pass spontaneously in less than 53% of cases.<ref name=Gettman2005 />

{{anchor|staghorn}}Stones that are large enough to fill out the renal calyces are called ''staghorn stones'' and are composed of [[struvite]] in a vast majority of cases, which forms only in the presence of [[Urease#As diagnostic test|urease-forming bacteria]]. Other forms that can possibly grow to become staghorn stones are those composed of cystine, calcium oxalate monohydrate, and uric acid.<ref name="Segura1997">{{cite journal | vauthors = Segura JW | title = Staghorn calculi | journal = The Urologic Clinics of North America | volume = 24 | issue = 1 | pages = 71–80 | date = February 1997 | pmid = 9048853 | doi = 10.1016/S0094-0143(05)70355-4 }}</ref>