kidney stone disease kidney stone disease kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. kidney stones typically form in the kidney and leave the body in the urine stream. a small stone may pass without causing symptoms. if a stone grows to more than 5 millimeters (0.2 inches), it can cause blockage of the ureter, resulting in sharp and severe pain in the lower back or abdomen. a stone may also result in blood in the urine, vomiting, or painful urination. about half of people who have had a kidney stone are likely to have another within ten years. kidney stone diseaseother namesurolithiasis, kidney stone, renal calculus, nephrolith, kidney stone disease,a kidney stone, 8 millimeters (0.3 in) in diameterspecialtyurology, nephrologysymptomssevere pain in the lower back or abdomen, blood in the urine, vomiting, nauseacausesgenetic and environmental factorsdiagnostic methodbased on symptoms, urine testing, medical imagingdifferential diagnosisabdominal aortic aneurysm, diverticulitis, appendicitis, pyelonephritispreventiondrinking fluids such that more than two liters of urine are produced per daytreatmentpain medication, extracorporeal shock wave lithotripsy, ureteroscopy, percutaneous nephrolithotomyfrequency22.1 million (2015)deaths16,100 (2015) most stones form by a combination of genetics and environmental factors. risk factors include high urine calcium levels, obesity, certain foods, some medications, calcium supplements, hyperparathyroidism, gout and not drinking enough fluids. stones form in the kidney when minerals in urine are at high concentration. the diagnosis is usually based on symptoms, urine testing, and medical imaging. blood tests may also be useful. stones are typically classified by their location: nephrolithiasis (in the kidney), ureterolithiasis (in the ureter), cystolithiasis (in the bladder), or by what they are made of (calcium oxalate, uric acid, struvite, cystine). in those who have had stones, prevention is by drinking fluids such that more than two liters of urine are produced per day. if this is not effective enough, thiazide diuretic, citrate, or allopurinol may be taken. it is recommended that soft drinks containing phosphoric acid (typically colas) be avoided. when a stone causes no symptoms, no treatment is needed; otherwise, pain control is usually the first measure, using medications such as nonsteroidal anti-inflammatory drugs or opioids. larger stones may be helped to pass with the medication tamsulosin or may require procedures such as extracorporeal shock wave lithotripsy, ureteroscopy, or percutaneous nephrolithotomy. kidney stones have affected humans throughout history with descriptions of surgery to remove them dating from as early as 600 bce. between 1% and 15% of people globally are affected by kidney stones at some point in their lives. in 2015, 22.1 million cases occurred, resulting in about 16,100 deaths. they have become more common in the western world since the 1970s. generally, more men are affected than women. the prevalence and incidence of the disease rises worldwide and continues to be challenging for patients, physicians, and healthcare systems alike. in this context, epidemiological studies are striving to elucidate the worldwide changes in the patterns and the burden of the disease and identify modifiable risk factors that contribute to the development of kidney stones. signs and symptoms diagram showing the typical location of renal colic, below the rib cage to just above the pelvis the hallmark of a stone that obstructs the ureter or renal pelvis is excruciating, intermittent pain that radiates from the flank to the groin or to the inner thigh. this is due to the transfer of referred pain signals from the lower thoracic splanchnic nerves to the lumbar splanchnic nerves as the stone passes down from the kidney or proximal ureter to the distal ureter. this pain, known as renal colic, is often described as one of the strongest pain sensations known. renal colic caused by kidney stones is commonly accompanied by urinary urgency, restlessness, hematuria, sweating, nausea, and vomiting. it typically comes in waves lasting 20 to 60 minutes caused by peristaltic contractions of the ureter as it attempts to expel the stone. 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 urolithiasis. postrenal azotemia and hydronephrosis can be observed following the obstruction of urine flow through one or both ureters. pain in the lower-left quadrant can sometimes be confused with diverticulitis because the sigmoid colon overlaps the ureter, and the exact location of the pain may be difficult to isolate due to the proximity of these two structures. risk factors dehydration from low fluid intake is a major factor in stone formation. individuals living in warm climates are at higher risk due to increased fluid loss. obesity, immobility, and sedentary lifestyles are other leading risk factors. high dietary intake of animal protein, sodium, sugars including honey, refined sugars, fructose and high fructose corn syrup, and excessive consumption of fruit juices may increase the risk of kidney stone formation due to increased uric acid excretion and elevated urinary oxalate levels (whereas tea, coffee, wine and beer may decrease the risk). kidney stones can result from an underlying metabolic condition, such as distal renal tubular acidosis, dent's disease, hyperparathyroidism, primary hyperoxaluria, or medullary sponge kidney. 3–20% of people who form kidney stones have medullary sponge kidney. kidney stones are more common in people with crohn's disease; crohn's disease is associated with hyperoxaluria and malabsorption of magnesium. a person with recurrent kidney stones may be screened for such disorders. this is typically done with a 24-hour urine collection. the urine is analyzed for features that promote stone formation. calcium oxalate a kidney stone (yellow) composed of calcium oxalatecalcium is one component of the most common type of human kidney stones, calcium oxalate. some studies suggest that people who take calcium or vitamin d as a dietary supplement have a higher risk of developing kidney stones. in the united states, kidney stone formation was used as an indicator of excess calcium intake by the reference daily intake committee for calcium in adults. in the early 1990s, a study conducted for the women's health initiative in the us found that postmenopausal women who consumed 1000 mg of supplemental calcium and 400 international units of vitamin d per day for seven 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. a 2004 study found that diets low in calcium are associated with a higher overall risk for kidney stone formation. for most individuals, other risk factors for kidney stones, such as high intakes of dietary oxalates and low fluid intake, play a greater role than calcium intake. other electrolytes calcium is not the only electrolyte that influences the formation of kidney stones. for example, by increasing urinary calcium excretion, high dietary sodium may increase the risk of stone formation. drinking fluoridated tap water may increase the risk of kidney stone formation by a similar mechanism, though further epidemiologic studies are warranted to determine whether fluoride in drinking water is associated with an increased incidence of kidney stones. high dietary intake of potassium appears to reduce the risk of stone formation because potassium promotes the urinary excretion of citrate, an inhibitor of calcium crystal formation. kidney stones are more likely to develop, and to grow larger, if a person has low dietary magnesium. magnesium inhibits stone formation. animal protein diets in western nations typically contain a large proportion of animal protein. eating animal protein creates an acid load that increases urinary excretion of calcium and uric acid and reduced citrate. urinary excretion of excess sulfurous amino acids (e.g., cysteine and methionine), uric acid, and other acidic metabolites from animal protein acidifies the urine, which promotes the formation of kidney stones. low urinary-citrate excretion is also commonly found in those with a high dietary intake of animal protein, whereas vegetarians tend to have higher levels of citrate excretion. low urinary citrate, too, promotes stone formation. vitamins the evidence linking vitamin c supplements with an increased rate of kidney stones is inconclusive. the excess dietary intake of vitamin c might increase the risk of calcium-oxalate stone formation. the link between vitamin d intake and kidney stones is also tenuous. excessive vitamin d supplementation may increase the risk of stone formation by increasing the intestinal absorption of calcium; correction of a deficiency does not. pathophysiology small crystals formed in the kidney. the most common crystals are made of calcium oxalate and they are generally 4–5 mm. staghorn kidney stones are considerably larger. 1. calcium and oxalate come together to make the crystal nucleus. supersaturation promotes their combination (as does inhibition.) 2. continued deposition at the renal papillae leads to the growth of the kidney stones. 3. kidney stones grow and collect debris. in the case where the kidney stones block all routes to the renal papillae, this can cause extreme discomfort and pain. 4. the complete staghorn stone forms and retention occurs. smaller solids that break off can become trapped in the urinary glands causing discomfort. 5. displaced stones travel through the ureter. if they cannot be broken down, they must be physically removed by a surgeon. 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 calculogenic (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 a liquid medium with no such surface), because it requires less energy. adhering to cells on the surface of a renal papilla, 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 calculogenic 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. 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 cause. randall's plaque while supersaturation of urine may lead to crystalluria, it does not necessarily promote the formation of a kidney stone because the particle may not reach the sufficient size needed for renal attachment. on the other hand, randall's plaques, which were first identified by alexander randall in 1937, are calcium phosphate deposits that form in the papillary interstitium and are thought to be the nidus required for stone development. in addition to randall's plugs, which form in the duct of bellini, these structures can generate reactive oxygen species that further enhance stone formation. pathogenic bacteria some bacteria have roles in promoting stone formation. specifically, urease-positive bacteria, such as proteus mirabilis can produce the enzyme urease, which converts urea to ammonia and carbon dioxide. this increases the urinary ph and promotes struvite stone formation. additionally, non-urease producing bacteria can provide bacteria components that can promote calcium oxalate crystallization, though this mechanism is poorly understood. 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