calcium-binding protein), tamm–horsfall protein, glycosaminoglycans, uropontin (a form of osteopontin), nephrocalcin (an acidic glycoprotein), prothrombin f1 peptide, and bikunin (uronic acid-rich protein). the biochemical mechanisms of action of these substances have not yet been thoroughly elucidated. however, when these substances fall below their normal proportions, stones can form from an aggregation of crystals. sufficient dietary intake of magnesium and citrate inhibits the formation of calcium oxalate and calcium phosphate stones; in addition, magnesium and citrate operate synergistically to inhibit kidney stones. the efficacy of magnesium in subduing stone formation and growth is dose-dependent. hypocitraturia hypocitraturia or low urinary-citrate excretion (variably defined as less than 320 mg/day) can be a contributing cause of kidney stones in up to 2/3 of cases. the protective role of citrate is linked to several mechanisms; citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. therapy with potassium citrate is commonly prescribed in clinical practice to increase urinary citrate and to reduce stone formation rates. alkali citrate is also used to increase urine citrate levels. it can be prescribed or found over-the-counter in pill, liquid or powder form. diagnosis diagnosis of kidney stones is made on the basis of information obtained from the history, physical examination, urinalysis, and radiographic studies. 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 spasmodic waves). pain in the back occurs when calculi produce an obstruction in the kidney. physical examination may reveal fever and tenderness at the costovertebral angle on the affected side. imaging studies calcium-containing stones are relatively radiodense, and they can often be detected by a traditional radiograph of the abdomen that includes the kidneys, ureters, and bladder (kub film). kub radiograph, 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. some 60% of all renal stones are radiopaque. 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. 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 ct scan imaging. a ct scan is also not typically recommended in children. otherwise a noncontrast helical ct scan with 5 millimeters (0.2 in) sections is the diagnostic method to use to detect kidney stones and confirm the diagnosis of kidney stone disease. near all stones are detectable on ct scans with the exception of those composed of certain drug residues in the urine, 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 injection of a contrast agent followed by a kub film. uroliths 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). 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. 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 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. despite these advantages, renal ultrasonography in 2009 was not considered a substitute for noncontrast helical ct scan in the initial diagnostic evaluation of urolithiasis. 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. 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 as an initial diagnostic test results in less radiation exposure and equally good outcome. bilateral kidney stones can be seen on this kub radiograph. there are phleboliths in the pelvis, which can be misinterpreted as bladder stones. axial ct scan of abdomen without contrast, showing a 3-mm stone (marked by an arrow) in the left proximal ureter renal ultrasonograph of a stone located at the pyeloureteric junction with accompanying hydronephrosis. measurement of a 5.6 mm large kidney stone in soft tissue versus skeletal ct window. laboratory examination struvite crystals found on microscopic examination of the urine laboratory investigations typically carried out include microscopic examination of the urine, which may show red blood cells, bacteria, leukocytes, urinary casts, and crystals; urine culture to identify any infecting organisms present in the urinary tract and 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 (hypercalcemia); 24 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. composition kidney stone type population circumstances color sensitivity details calcium oxalate 80% when urine is acidic (decreased ph) black/dark brown 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 5–10% when urine is alkaline (high ph) dirty white radio-opaque tends to grow in alkaline urine especially when proteus bacteria are present. uric acid 5–10% when urine is persistently acidic yellow/reddish brown radiolucent diets rich in animal proteins and purines: substances found naturally in all food but especially in organ meats, fish, and shellfish. struvite 10–15% infections in the kidney and when urine is alkaline (high ph) dirty white radio-opaque prevention of struvite stones depends on staying infection-free. diet has not been shown to affect struvite stone formation. cystine 1–2% rare genetic disorder pink/yellow radio-opaque cystine, an amino acid (one of the building blocks of protein), leaks through the kidneys and into the urine to form crystals. xanthine extremely rare brick red radiolucent 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) multiple kidney stones composed of uric acid and a small amount of calcium oxalate 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. factors that promote the precipitation of oxalate crystals in the urine, such as primary hyperoxaluria, are associated with the development of calcium oxalate stones. the formation of calcium phosphate stones is associated with conditions such as hyperparathyroidism and renal tubular acidosis. 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. 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. struvite stones about 10–15% of urinary calculi are composed of struvite (ammonium magnesium phosphate, nh4mgpo4·6h2o). 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 metabolize urea into ammonia and carbon dioxide. this 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, klebsiella, serratia, and enterobacter. these infection stones are commonly observed in people who have factors that predispose them to urinary tract infections, such as those with spinal cord injury and other forms of neurogenic bladder, ileal conduit urinary diversion, vesicoureteral reflux, and 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. struvite stones (triple-phosphate/magnesium ammonium phosphate) have a 'coffin lid' morphology by microscopy. uric acid stones about 5–10% of all stones are formed from uric acid. people with certain metabolic abnormalities, including obesity, 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 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 radiolucent stone in the face of persistent urine acidity, in conjunction with the finding of uric acid crystals in fresh urine samples. 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 colon resection. uric acid stones appear as pleomorphic crystals, usually diamond-shaped. they may also look like squares or rods which are polarizable. other types people with certain rare 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, alkaptonurics produce homogentisic acid stones, and iminoglycinurics produce stones of glycine, proline, and hydroxyproline. 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, sulfadiazine, and triamterene. location illustration of kidney stones urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder. nephrolithiasis refers to the presence of such stones in the kidneys. calyceal calculi are aggregations in either the 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 stones. size radiograph showing a large staghorn calculus involving the major calyces and renal pelvis in a person with severe scoliosis stones less than 5 mm (0.2 in) in diameter pass spontaneously in up to 98% of cases, while those measuring 5 to 10 mm (0.2 to 0.4 in) in diameter pass spontaneously in less than 53% of cases. stones that