Kidney stones

Kidney stones
Kidney stones (called renal calculi (from Latin ren, renes, "kidney" and calculi, "pebbles" in medical parlance) are solid concretions or crystal aggregations formed in the kidneys from dietary minerals in the urine. Kidney stones are typically classified by their location in the kidney (nephrolithiasis), ureter (ureterolithiasis), or bladder (cystolithiasis), or by their chemical composition (calcium-containing, struvite, uric acid, or other compounds). Kidney stones are a significant source of morbidity. 80% of those with kidney stones are men. Men most commonly experience their first episode between age 30–40 years, while for women the age at first presentation is somewhat later.
Kidney stones typically leave the body by passage in the urine stream, and many stones are formed and passed without causing symptoms. If stones grow to sufficient size (usually at least 2–3 millimeters), they can cause obstruction of the ureter. Ureteral obstruction causes postrenal azotemia and hydronephrosis (distension and dilation of the renal pelvis and calyces), as well as spasm of the ureter. This leads to pain, most commonly felt in the flank, lower abdomen and groin (a condition called renal colic). Renal colic can be associated with nausea, vomiting, fever, blood in the urine, pus in the urine, and painful urination. Renal colic typically comes in waves lasting 20 to 60 minutes, beginning in the flank or lower back and often radiating to the groin or genitals. The diagnosis of kidney stones is made on the basis of information obtained from the history, physical examination, urinalysis, and radiographic studies. ultrasound examination and blood tests may also aid in the diagnosis.
When a stone causes no symptoms, watchful waiting is a valid option. For symptomatic stones, pain control is usually the first measure, using medications such as non-steroidal anti-inflammatory drugs (NSAIDs) or opioids. More severe cases may require surgical intervention. For example, some stones can be shattered into smaller fragments using extracorporeal shock wave lithotripsy (ESWL). Some cases require more invasive forms of surgery. Examples of these are cystoscopic procedures such as laser lithotripsy, or percutaneous techniques such as percutaneous nephrolithotomy. Sometimes, a tube may be placed in the ureter (a ureteral stent) to bypass the obstruction in the ureter and alleviate the symptoms.

Classification
Kidney stones are typically classified by their location or their chemical composition.
Location

Urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder. Nephrolithiasis (from Greek νεφρός (nephros, "kidney") and λίθoς (lithos, "stone")) refers to the presence of such calculi in the kidneys. Calyceal) calculi refers to aggregations in either the minor or major calyx, parts of the kidney which pass urine into the ureter (the tube connecting the kidneys to the urinary bladder). The condition is called ureterolithiasis when a calculus or calculi are located in the ureter. Stones may also form or pass into the bladder, a condition referred to as cystolithiasis.

Chemical composition
By far the most common type of kidney stones worldwide are those which contain 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.
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 which 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 calculi requiring invasive surgery such as percutaneous nephrolithotomy for definitive treatment.
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. Uric acid stones may form in association with conditions that cause hyperuricosuria (an excessive amount of uric acid in the urine) with or without high 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.
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. People afflicted with xanthinuria often produce stones composed of xanthine. People afflicted with 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 patients currently being treated with agents such as indinavir, sulfadiazine and triamterene.

Signs and symptoms
Signs of urolithiasis include oliguria (reduced urinary volume) caused by obstruction of the bladder or urethra by a stone or rarely, simultaneous obstruction of both ureters by two separate stones. Postrenal azotemia and hydronephrosis (distension and dilation of the renal pelvis and calyces)[  can be observed following the obstruction of urine flow through one or both ureters.[
Hallmark symptoms of kidney stones include renal colic, fever, hematuria, pyuria, and dysuria. Pain caused by kidney stones, referred to as renal colic, is often described as one of the strongest pain sensations felt by humans. Renal colic, which typically comes in waves lasting 20 to 60 minutes, is caused by peristaltic contractions of the ureter as it attempts to expel the stone. It typically begins in the flank or lower back, often radiating to the groin or in men, to the testes. The embryological link between the urinary tract, the genital system and the gastrointestinal tract is the basis of the radiation of pain to the gonads, as well as the nausea and vomiting that are also common in nephrolithiasis and ureterolithiasis.

Causes
Supersaturation of urine
When the urine becomes supersaturated (when the urine solvent contains more solutes than it can hold in solution) with one or more crystal-forming substances, a seed crystal may form through the process of nucleation. Heterogeneous nucleation (where there is a solid surface present on which a crystal can grow) proceeds more rapidly than homogeneous nucleation (where a crystal must grow in liquid medium with no such surface), because it requires less energy. Adhering to cells on the surface of a renal papillae, a seed crystal can grow and aggregate into an organized mass. Depending on the chemical composition of the crystal, the stone-forming process may proceed more rapidly when the urine pH is unusually high or low.
Supersaturation of the urine with respect to a crystal-forming compound is pH-dependent. For example, at a pH of 7.0, the solubility of uric acid in urine is 158 mg/100 mL. Reducing the pH to 5.0 decreases the solubility of uric acid to less than 8 mg/100 mL. One can readily see that the formation of uric acid stones requires a combination of hyperuricosuria (high urine uric acid levels) and low urine pH; hyperuricosuria alone is not associated with uric acid stone formation if the urine pH is alkaline. Supersaturation of the urine is a necessary but not a sufficient condition for the development of any urinary calculus. Supersaturation is likely the underlying cause of uric acid and cystine stones, but calcium-based stones (especially calcium oxalate stones) may have a more complex etiology.
Inhibitors of stone formation
Normal urine contains chelating agents such as citrate that inhibit the nucleation, growth, and aggregation of calcium-containing crystals. Other endogenous inhibitors include calgranulin (an S-100 calcium binding protein), Tamm-Horsfall protein (THP), 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 out of an aggregation of crystals.
Kidney stones often result from a combination of factors, rather than a single, well-defined cause. Stones are more common in people whose diet is very high in animal protein or vitamin C or who do not consume enough water or calcium. They can result from an underlying metabolic condition, such as renal tubular acidosis, Dent's disease, hyperparathyroidism, primary hyperoxaluria or medullary sponge kidney.  Kidney stones are also more common in patients with Crohn's disease.[27] Patients with recurrent kidney stones are often screened for these disorders. This is typically done with a 24–hour urine collection that is chemically analyzed for deficiencies and excesses that promote stone formation.
Calcium
Some studies suggest that people who take supplemental calcium have a higher risk of developing kidney stones, and these findings have been used as the basis for setting the Recommended Daily Intake (RDI) for calcium in adults. In the Women's Health Initiative, postmenopausal women who consumed 1,000 milligrams of supplemental calcium and 400 IU of vitamin D per day for 7 years had a 17% higher risk of developing kidney stones than subjects taking a placebo. The Nurses' Health Study also showed an association between supplemental calcium intake and kidney stone formation.
Unlike supplemental calcium, high intakes of dietary calcium do not appear to cause kidney stones and may actually protect against their development. This is perhaps related to the role of calcium in binding ingested oxalate in the gastrointestinal tract. As the amount of calcium intake decreases, the amount of oxalate available for absorption into the bloodstream increases; this oxalate is then excreted in greater amounts into the urine by the kidneys. In the urine, oxalate is a very strong promoter of calcium oxalate precipitation, about 15 times stronger than calcium. In fact, current evidence suggests that the consumption of diets low in calcium is associated with a higher overall risk for the development of kidney stones. For most individuals however, other risk factors for kidney stones, such as high intakes of oxalates from food and low intakes of fluid, probably play a bigger role than calcium intake.
Role of dietary animal protein
Diets in Western nations typically contain more animal protein than the body needs, and as the excess amino acids are broken down and excreted, the sulfurous amino acids (typically derived from animal rather than vegetarian foods) cause calcium to be excreted in the urine; calcium is one component of the most common type of human kidney stones, calcium oxalate. Red meat also contains acids that need to be excreted and this acidity constitutes another risk factor for kidney stones. High intake of animal protein also presents a greater uric acid load to be excreted by the kidney. This in turn acidifies the urine, increasing the risk of uric acid stones. In either case, the body often balances this acidic urinary pH by leaching calcium from the bones.
Other
There is some evidence that water fluoridation may increase the risk of kidney stone formation. In one study, patients with symptoms of skeletal fluorosis were 4.6 times as likely to develop kidney stones.
Despite a widely-held belief in the medical community that ingestion of vitamin C supplements is associated with an increased incidence of kidney stones, the evidence for a causal relationship between vitamin C supplements and kidney stones is inconclusive.
There are no conclusive data demonstrating a cause and effect relationship between alcohol consumption and kidney stones. However, some have theorized that certain behaviors associated with frequent and binge drinking can lead to systemic dehydration, which can in turn lead to the development of kidney stones.[43]
The American Urological Association has projected that increasing global temperatures will lead to an increased incidence of kidney stones in the United States by expanding the "kidney stone belt" of the southern United States. Astronauts seem to show a higher risk of developing kidney stones during or after space flights of long duration.
Prevention
Specific therapy should be tailored to the type of stones involved. Dietary intake can have a profound influence on the development of kidney stones. Preventive strategies may include dietary modifications and medication with the goal of reducing the excretory load on the kidneys.
A key principle for the prevention of kidney stones is to increase urine volume. The relative probability of kidney stone formation decreases as urinary volume increases. Because of this, maintenance of dilute urine by means of vigorous fluid therapy is beneficial in all forms of nephrolithiasis. Fluid intake should be sufficient to maintain a urine output of 2–3 liters per day. A high fluid intake has been associated with a 40% reduction in recurrence risk.
Available data suggest that the type of fluid ingested is important. For example, orange juice may help prevent calcium oxalate stone formation, blackcurrant juice may help prevent uric acid stones, and cranberry juice may help with struvite stones. Lemons have the highest concentration of citrate of any citrus fruit, and daily consumption of lemonade has been shown to decrease the rate of stone formation. Beer appears to decrease the rate of stone formation, while grapefruit juice appears to increase the risk. One study indicated that intake of caffeinated beverages increases risk of kidney stones. While it may be advised to avoid caffeinated cola beverages because of their high phosphate content, this does not include coffee or tea. In fact, prospective cohort studies of coffee and tea actually indicate that they may prevent kidney stones. Though caffeine does acutely increase urinary calcium excretion, several independent epidemiologic studies have shown that coffee intake overall is protective against the formation of stones.
Calcium binds with available oxalate in the gastrointestinal tract, thereby preventing its absorption into the bloodstream. A randomized controlled trial published in 2002 assigned men with hypercalciuria to follow either a diet containing a normal amount of calcium (30 mmol per day) but with restricted intake of animal protein and salt, or a low-calcium (10 mmol per day) diet. At 5 years, the group on the normal calcium, low animal protein and low salt diet had a 51% lower rate of stone recurrence than those following a low-calcium diet. Some nephrologists and urologists recommend chewing calcium tablets during meals containing oxalate foods. Calcium citrate supplements can be taken with meals if dietary calcium cannot be increased by other means. The preferred calcium supplement for people at risk of stone formation is calcium citrate because it helps to increase urinary citrate excretion.
Aside from vigorous oral hydration and consumption of more dietary calcium, prevention strategies include avoidance of large doses of vitamin C and restriction of oxalate-rich foods. Measurements of food oxalate content have been difficult and issues remain about the proportion of oxalate that is bioavailable, versus a proportion that is not absorbed by the intestine. Oxalate-rich foods are usually restricted to some degree, particularly in patients with high urinary oxalate levels, but no randomized controlled trial of oxalate restriction has been performed to test that hypotheses.