INTRODUCTION:

Urolithiasis (Kidney Stone)^1,2

Kidney stones (calculi) are masses of crystals and protein and are common causes of urinary tract obstruction in adults. The process of forming a kidney stone is called as Nephrolithiasis. Kidney stones may be Calcium oxalate/calcium phosphate stones, Magnesium ammonium phosphate stones, Uric acid stones and Cystine stones.

Figure No. 1: Kidney stone

A kidney stone, also known as a renal calculus (from the Latin language, "kidneys" and calculus, "pebble") is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine.Urinary 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). About 80% of those with kidney stones are men. Men most commonly experience their first episode between 20-30 years of age, 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 3 millimeters (0.12 in), 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 (the area between the ribs and hip), 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 nonsteroidal anti-inflammatory drugs or opioids. More severe cases may require surgical intervention. For example, some stones can be shattered into smaller fragments using extracorporeal shock wave lithotripsy. 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 (ureteral stent) may be placed in the ureter to bypass the obstruction and alleviate the symptoms, as well as to prevent ureteral stricture after ureteroscopic stone removal.

Signs and symptoms of Urolithiasis

The hallmark of stones that obstruct the ureter or renal pelvis is excruciating, intermittent pain that radiates from the flank to the groin or to the genital area and inner thigh. This particular type of 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.

CAUSES OF UROLITHIASIS

Dietary factors that increase the risk of stone formation include low fluid intake and high dietary intake of animal protein, sodium, refined sugars, fructose and high fructose corn syrup, oxalate, grape fruit juice, apple juice, and cola drinks.

Calcium: Calcium is one component of the most common type of human kidney stones, calcium oxalate. Some studies suggest 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 for calcium in adults. In the Women's Health Initiative, 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. In fact, current evidence suggests 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 dietary oxalates and low fluid intake, probably play a greater role than calcium intake.

Other electrolytes: Aside from calcium, other electrolytes appear to influence the formation of kidney stones. For example, by increasing urinary calcium excretion, high dietary sodium may increase the risk of stone formation. Fluoridation of drinking 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. On the other hand, high dietary intake of potassium appears to reduce the risk of stone formation because potassium promotes the urinary excretion of citrate, an inhibitor of urinary crystal formation. High dietary intake of magnesium also appears to reduce the risk of stone formation somewhat, because like citrate, magnesium is also an inhibitor of urinary crystal formation.

Animal protein: Diets in Western nations typically contain more animal protein than the body needs. 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. The body often balances this acidic urinary pH by leaching calcium from the bones, which further 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.

Vitamins: 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. While excess dietary intake of vitamin C might increase the risk of calcium oxalate stone formation, in practice this is rarely encountered. 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, but there is no evidence that correction of vitamin D deficiency increases the risk of stone formation.

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. 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.

PATHOPHYSIOLOGY OF UROLITHIASIS²¹

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 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 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, 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.

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 who do not consume enough water or calcium. They can result from an underlying metabolic condition, such as distal renal tubular acidosis, Dent's disease, hyperparathyroidism, primary hyperoxaluria or medullary sponge kidney. In fact, studies show about 3% to 20% of people who form kidney stones have medullary sponge kidney. Kidney stones are also more common in people with Crohn's disease. People 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.

Diagnosis of Urolithiasis

Bilateral kidney stones can be seen on this KUB radiograph. Note the presence of 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.

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 radio-dense, and they can often be detected by a traditional radiograph of the abdomen that includes the kidneys, ureters, and bladder (KUB film). Some 60% of all renal stones are radio-paque. In general, calcium phosphate stones have the greatest density, followed by calcium oxalate and magnesium ammonium phosphate stones. Cystine calculi are only faintly radio-dense, while uric acid stones are usually entirely radiolucent.

Where available, a non-contrast helical CT scan with 5 millimeters (0.20 in) sections is the diagnostic modality of choice in the radiographic evaluation of suspected nephrolithiasis. All stones are detectable on CT scans except very rare stones 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). Ultrasound imaging of the kidneys can sometimes be useful, as it gives details about the presence of hydronephrosis, suggesting the stone is blocking the outflow of urine. Radiolucent stones, which do not appear on CT scans, 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 is not currently 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), as well as other serious disorders that could be causing the symptoms.

Laboratory examination

Figure No. 2: Struvite crystals in microscopic examination of urine

Typical Laboratory Investigations of Urolithiasis

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 blood 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.

Classification of Kidney stones

Kidney stones are typically classified by their location and chemical composition given in Table No.1.

Chemical composition of Kidney stones

Figure No.3: Crystals of Weddellite

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).

Figure No.4: Uric acid and Calcium oxalate (Multiple kidney stones composed of uric acid and a small amount of calcium oxalate)

Calcium-containing stones

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 disease or 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 which usually presents in childhood.

Calcium oxalate stones appear as 'envelopes' microscopically. They may also form 'dumbells.'

Struvite stones

About 10–15% of urinary calculi are composed of struvite (ammonium magnesium phosphate, NH4MgPO4·6H2O). Struvite stones (also known as "infection stones", surease 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’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), patients with inflammatory bowel disease (Crohn disease, ulcerative colitis) tend to have hyperoxaluria and form oxalate stones. These patients 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.

Patients with hyperuricosuria can be treated with allopurinol which will reduce urate formation. Urine alkalinization may also be helpful in this setting.

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 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 people currently being treated with agents such as indinavir, sulfadiazine and triamterene.

Location of Kidney stones

This radiograph shows a large staghorn calculus involving the major calyces and renal pelvis in a person with severe scoliosis. Struvite stones can grow rapidly, forming large calyceal staghorn calculi that can require invasive surgery such as percutaneous nephrolithotomy or even anatrophic nephrolithotomy for definitive treatment. Urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder. Nephrolithiasis (from the Greek meaning (nephros, "kidney") and (lithos, "stone") refers to the presence of such calculi in the kidneys. Calyceal calculi refer to 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 cystolithiasis.

Prevention of Urolithiasis

Dietary measures

Specific therapy should be tailored to the type of stones involved. Diet can have a profound influence on the development of kidney stones. Preventive strategies include some combination of dietary modifications and medications with the goal of reducing the excretory load of calculogenic compounds on the kidneys. Current dietary recommendations to minimize the formation of kidney stones include:

Increasing fluid intake of citrate-rich foods (especially citrate-rich fluids such as lemonade and orange juice), with the objective of increasing urine output to more than two liters per day.

Attempt to maintain a calcium (Ca) intake of 1000 – 1200 mg per day.

Limiting sodium (Na) intake to less than 2300 mg per day.

Limiting vitamin C intake to less than 1000 mg per day.

Limiting animal protein intake to no more than two meals daily, with less than 170–230 g per day. (A positive association between animal protein consumption and recurrence of kidney stones has been shown in men.) Limiting consumption of foods containing high amounts of oxalate (such as spinach, strawberries, nuts, rhubarb, wheat germ, dark chocolate, cocoa, brewed tea). Maintenance of dilute urine by means of vigorous fluid therapy is beneficial in all forms of nephrolithiasis, so increasing urine volume is a key principle for the prevention of kidney stones. Fluid intake should be sufficient to maintain a urine output of at least 2 l (68 US fl oz) per day. A high fluid intake has been associated with a 40% reduction in recurrence risk. Calcium binds with available oxalate in the gastrointestinal tract, thereby preventing its absorption into the bloodstream, and reducing oxalate absorption decreases kidney stone risk in susceptible people. Because of this, 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, other prevention strategies include avoidance of large doses of supplemental vitamin C and restriction of oxalate-rich foods such as leaf vegetables, rhubarb, soy products and chocolate. However, no randomized, controlled trial of oxalate restriction has yet been performed to test the hypothesis that oxalate restriction reduces the incidence of stone formation. Some evidence indicates magnesium intake decreases the risk of symptomatic nephrolithiasis. Increase water intake may reduce the risk of recurrence of kidney stones but more studies are needed.¹⁹

Urine alkalinization

The mainstay for medical management of uric acid stones is alkalinization (increasing the pH) of the urine. Uric acid stones are among the few types amenable to dissolution therapy, referred to as chemolysis. Chemolysis is usually achieved through the use of oral medications, although in some cases, intravenous agents or even instillation of certain irrigating agents directly onto the stone can be performed, using antegrade nephrostomy or retrograde ureteral catheters. Acetazolamide (Diamox) is a medication that alkalinizes the urine. In addition to acetazolamide or as an alternative, certain dietary supplements are available that produce a similar alkalinization of the urine. These include sodium bicarbonate, potassium citrate, magnesium citrate, and Bicitra (a combination of citric acid monohydrate and sodium citrate dihydrate). Aside from alkalinization of the urine, these supplements have the added advantage of increasing the urinary citrate level, which helps to reduce the aggregation of calcium oxalate stones.

Increasing the urine pH to around 6.5 provides optimal conditions for dissolution of uric acid stones. Increasing the urine pH to a value higher than 7.0 increases the risk of calcium phosphate stone formation. Testing the urine periodically with nitrazine paper can help to ensure the urine pH remains in this optimal range. Using this approach, stone dissolution rate can be expected to be around 10 mm (0.39 in) of stone radius per month.

Diuretics

One of the recognized medical therapies for prevention of stones is the thiazide and thiazide-like diuretics, such as chlorthalidone or indapamide. These drugs inhibit the formation of calcium-containing stones by reducing urinary calcium excretion. Sodium restriction is necessary for clinical effect of thiazides, as sodium excess promotes calcium excretion. Thiazides work best for renal leak hypercalciuria (high urine calcium levels), a condition in which high urinary calcium levels are caused by a primary kidney defect. Thiazides are useful for treating absorptive hypercalciuria, a condition in which high urinary calcium is a result of excess absorption from the gastrointestinal tract.

Allopurinol

For people with hyperuricosuria and calcium stones, allopurinol is one of the few treatments that have been shown to reduce kidney stone recurrences. Allopurinol interferes with the production of uric acid in the liver. The drug is also used in people with gout or hyperuricemia (high serum uric acid levels). Dosage is adjusted to maintain a reduced urinary excretion of uric acid. Serum uric acid level at or below 6 mg/100 ml) is often a therapeutic goal. Hyperuricemia is not necessary for the formation of uric acid stones; hyperuricosuria can occur in the presence of normal or even low serum uric acid. Some practitioners advocate adding allopurinol only in people in whom hyperuricosuria and hyperuricemia persist, despite the use of a urine-alkalinizing agent such as sodium bicarbonate or potassium citrate.

MANAGEMENT OF UROLITHIASIS

Medical

Stone size influences the rate of spontaneous stone passage. For example, up to 98% of small stones (less than 5 mm (0.20 in) in diameter) may pass spontaneously through urination within four weeks of the onset of symptoms, but for larger stones (5 to 10 mm (0.20 to 0.39 in) in diameter), the rate of spontaneous passage decreases to less than 53%. Initial stone location also influences the likelihood of spontaneous stone passage. Rates increase from 48% for stones located in the proximal ureter to 79% for stones located at the vesicoureteric junction, regardless of stone size. Assuming no high-grade obstruction or associated infection is found in the urinary tract, and symptoms are relatively mild, various nonsurgical measures can be used to encourage the passage of a stone. Repeat stone formers benefit from more intense management, including proper fluid intake and use of certain medications. In addition, careful surveillance clearly is required to maximize the clinical course for people who are stone formers.

Analgesia

Management of pain often requires intravenous administration of NSAIDs or opioids. Orally administered medications are often effective for less severe discomfort.

Expulsion therapy

The use of medications to speed the spontaneous passage of ureteral calculi is referred to as medical expulsive therapy. Several agents, including alpha adrenergic blockers (such as tamsulosin) and calcium channel blockers (such as nifedipine), have been found to be effective. A combination of tamsulosin and a corticosteroid may be better than tamsulosin alone. These treatments also appear to be a useful adjunct to lithotripsy.

Surgical

A lithotriptor machine is seen in an operating room; other equipment is seen in the background, including an anesthesia machine and a mobile fluoroscopic system (or "C-arm").

Most stones less than 5 mm (0.20 in) pass spontaneously. Prompt surgery may, nonetheless, be required with persons with only one working kidney, bilateral obstructing stones, and a urinary tract infection and thus, it is presumed, an infected kidney, or intractable pain. Beginning in the mid-1980s, less invasive treatments such as extracorporeal shock wave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy began to replace open surgery as the modalities of choice for the surgical management of urolithiasis. More recently, flexible ureteroscopy has been adapted to facilitate retrograde nephrostomy creation for percutaneous nephrolithotomy. This approach is still under investigation, though early results are favorable.

Ureteroscopic surgery

Ureteroscopy has become increasingly popular as flexible and rigid fiberoptic ureteroscopes have become smaller. One ureteroscopic technique involves the placement of a ureteral stent (a small tube extending from the bladder, up the ureter and into the kidney) to provide immediate relief of an obstructed kidney. Stent placement can be useful for saving a kidney at risk for postrenal acute renal failure due to the increased hydrostatic pressure, swelling and infection (pyelonephritis and pyonephrosis) caused by an obstructing stone. Ureteral stents vary in length from 24 to 30 cm (9.4 to 12 in) and most have a shape commonly referred to as a "double-J" or "double pigtail", because of the curl at both ends. They are designed to allow urine to flow past an obstruction in the ureter. They may be retained in the ureter for days to weeks as infections resolve and as stones are dissolved or fragmented by ESWL or by some other treatment. The stents dilate the ureters, which can facilitate instrumentation, and they also provide a clear landmark to aid in the visualization of the ureters and any associated stones on radiographic examinations. The presence of indwelling ureteral stents may cause minimal to moderate discomfort, frequency or urgency incontinence, and infection, which in general resolves on removal. Most ureteral stents can be removed cystoscopically during an office visit under topical anesthesia after resolution of the urolithiasis.

More invasive operations

Percutaneous nephrolithotomy or, rarely, anatrophic nephrolithotomy, is the treatment of choice for large or complicated stones (such as calyceal staghorn calculi) or stones that cannot be extracted using less invasive procedures.

Epidemiology

Urolithiasis is a significant source of morbidity, affecting all geographical, cultural, and racial groups. The lifetime risk is about 10 to 15% in the developed world, but can be as high as 20 to 25% in the Middle East. The increased risk of dehydration in hot climates, coupled with a diet 50% lower in calcium and 250% higher in oxalates compared to Western diets, accounts for the higher net risk in the Middle East. In the Middle East, uric acid stones are more common than calcium-containing stones.

In North America and Europe, the annual incidence (number of new cases per year) of kidney stones is roughly 0.5%. In the United States, the prevalence (frequency in the population) of urolithiasis has increased from 3.2% to 5.2% from the mid-1970s to the mid-1990s. The total cost for treating urolithiasis was US$2 billion in 2003. About 80% of those with kidney stones are men; most stones in women are due to either metabolic defects (such as cystinuria) or infection. Men most commonly experience their first episode between 30 and 40 years of age, whereas for women, the age at first presentation is somewhat later. The age of onset shows a bimodal distribution in women, with episodes peaking at 35 and 55 years. Recurrence rates are estimated at 50% over a 10-year and 75% over 20-year period, with some people experiencing ten or more episodes over the course of a lifetime.

History of Urolithiasism

The existence of kidney stones was first recorded thousands of years ago, and lithotomy for the removal of stones is one of the earliest known surgical procedures. In 1901, a stone discovered in the pelvis of an ancient Egyptian mummy was dated to 4,800 BC. Medical texts from ancient Mesopotamia, India, China, Persia, Greece, and Rome all mentioned calculous disease. Part of the Hippocratic Oath suggests there were practicing surgeons in ancient Greece to whom physicians were to defer for lithotomies. The Roman medical treatise De Medicina by Aulus Cornelius Celsus contained a description of lithotomy, and this work served as the basis for this procedure until the 18th century.

Famous people who were kidney stone formers include Napoleon I, Napoleon III, Peter the Great, Louis XIV, George IV, Oliver Cromwell, Lyndon B. Johnson, Benjamin Franklin, Michel de Montaigne, Francis Bacon, Isaac Newton, Samuel Pepys, William Harvey, Herman Boerhaave, and Antonio Scarpa.

New techniques in lithotomy began to emerge starting in 1520, but the operation remained risky. After Henry Jacob Bigelow popularized the technique of litholapaxy in 1878, the mortality rate dropped from about 24% to 2.4%. However, other treatment techniques continued to produce a high level of mortality, especially among inexperienced urologists. In 1980, Dornier MedTech introduced extracorporeal shock wave lithotripsy for breaking up stones via acoustical pulses, and this technique has since come into widespread use.

Research directions

Crystallization of calcium oxalate appears to be inhibited by certain substances in the urine that retard the formation, growth, aggregation, and adherence of crystals to renal cells. By purifying urine using salt precipitation, isoelectric focusing, and size-exclusion chromatography, some researchers have found that calgranulin, a protein formed in the kidney, is a potent inhibitor of the in vivo formation of calcium oxalate crystals. Considering its extremely high levels of inhibition of growth and aggregation of calcium oxalate crystals, calgranulin might be an important intrinsic factor in the prevention of nephrolithiasis.

Plants with Urolithiatic activity³

List of Other Plants Useful in Dissolving Kidney Stone

1. Aerva javanica, Amaranthaceae Herb- diuretic, Purgative, Demulcent.

2. Ammania baccifera, Lythraceae- Ringworm, Parasitic skin affection, Anti-typhoid, Anti- tubercular properties.

3. Arctostaphylos uraursi, Asteraceaer- Diuretic, Diaphoretic, Gout, Skin affection.

4. Ascyrum hypericoides, Asclepidaceae- Emetic and Cathartic.

5. Asparagus racemosus, Liliaceae- Herb tonic, Diuretic, Galactagogue.

6. Berginia ligulata, Saxifragaceae- Astringent. Diuretic, Lithontriptic.

7. Bridolia Montana, Euphobiaceae- Bark Astringent, Anthelminetic.

8. Caesalpinia huga, Caesalpinioceae- RootDiuretic, Lithontriptic.

9. Chelidonium majus, Papaveraceae- Diuretic, Antispasmodic, bitter.

10. Chimaphila numbellata, Cruciferae - Diuretic, Expectorant, Stimulant.

11. Curcuma longa, Zingiberaceae- Diuretic, Choleretic, Hepatoprotective.

12. Desmodium styracifolium, Papilionaceae- Roots Emmenagogue, Stomachic.

13. Dolichos biflorus, Leguminoceae- Diuretic, Astringent, Tonic.

14. Eupatorium puipurecum Compositae cathartic, emetic, diuretic, Antiscorbutic.

Dolichos biflorus

Seeds of the drug Dolichos biflorus belonging to family Leguminosae, is supposed to be the best herb to cure urolithiatiasis from ancient times. It is commonly known as Kulatha (Sanskrit), Horsegram (English), Kurti-kalai (Bengali), Kollu (Tamil) and Kulthi (Hindi).

Figure No.5: Dolichos biflorus Plant

Table No.2: Macroscopic Evaluation of Dolichos biflorus

Sr. No.	Features	Observation
1	Plant Type	Herb
2	Plant Height	10-15 m
3	Type of Leaf	Narrow, flat
4	Leaf Base	Symmetrical
5	Leaf Apex	Obtuse
6	Leaf Margin	Oblanceolate
7	Leaf Surface	Hairy
8	Leaf Venation	Reticulate
9	Leaf Arrangement	Branched
10	Leaf Color
	Upper Surface	Green
	Lower Surface	Light green
11	Stem Origin	Simple or Branched from the base
12	Type of stem	Non Woody
13	Roots	Shallow roots, Tap roots
14	Seed	Flattened, Ellipsoid

MICROSCOPIC STUDY OF HERB DOLICHOS BIFLORUS

Transverse section of Dolichos biflorus leaves

Dolichos biflorus is a dorsiventral leaf. A thin transverse section shows Upper epidermis, lower epidermis, mesophyll and vascular bundles. Upper epidermis contains single layer of large and thick walled anticlinal cells and covering trichomes. Lower epidermisalsoidal contain single layer of cells with thin cuticle and covering trichomes. Mesophyll is the ground tissue lying between the two epidermal layers. It is differentiated into Palisade parenchyma (single layer below the upper epidermis only) and spongy parenchyma (five to six layers below the palisade layer) with large intercellular spaces. Vascular bundles are arranged centrally in the midrib region and they consist of xylem (which lies towards the upper epidermis) and Phloem (which lies towards the lower epidermis). There are six to seven layers of collenchymatous cells below the vascular bundle and towards the lower epidermis in the mid rib region.

Transverse section of Dolichos biflorus root

From the outer to inner side, transverse section of root of Dolichos biflorus shows epiblema, exodermis, cortex, endodermis, pericycle, vascular bundle and pith. It contains covering trichomes, originated from epiblema layer.

Epidermal cells are thin-walled and are devoid of cuticle, cortex is made up of parenchymatous cells; very small thin-walled cells of pericycle of single layer; vascular bundle have radial arrangement, having alternate arrangement of xylem and phloem; protoxylem is present towards pericycle, while metaxylem is towards pith; Conjunctive tissue is present in between xylem and phloem; pith ells is present in a small area in the centre of the root.

Transverse section of Dolichos biflorus Stem

Dolichos biflorus is a dicotyledonous herb. It has got the outermost layer, which is known as epidermis, and it consists of flattened tangential cells. Exactly below the epidermis, there is cortex. Cortex can be divided into three parts, from outer to inner side – hypodermis made up of collenchyma, general cortex made up of parenchyma and endodermis. Endodermis contains numerous starch grains, therefore it is known as “Starch sheath”. Pericycle is the region lying between endodermis and vascular bundle and it is made up of sclerenchyma and intervening parenchymatous cells. Below the pericycle there are vascular bundles which consist of secondaryphloem, secondary xylem and cambium. Protoxylem is present towards pericycle, while metaxylem is towards pith. Pith is a small area in the centre of the stem consisting of well developed parenchymatous cells.

Powder microscopy of Dolichos biflorus powder

It was creamy yellow colour Powder had shown fragments of spiral xylem vessels; epidermal cells in surface view; fibers and pieces of unicellular, multicellular trichomes present.

Ethnomedical Review of herb Dolichos biflorus^{4-8, 30-38}

Use ofDolichos biflorus have been employed traditionally from ancient time for the treatment of kidney stone and other diseases such as in asthma, colic pain, cold, cough, hiccoughs, stones in kidney and gallbladder, leucorrhoea and menstrual disorders, Eye diseases, Piles, Worm infestation, Tumors.

Chemical review of herb Dolichos biflorus

Flavonoids from D. biflorus (Leguninosae) were isolated and screened for antilipidemic activity on rabbits fed with high fat diet (HFD). Methanolic extract was fractionated with hexane, chloroform ethyl acetate and methanol. Ethyl acetate fration which showed maximum flavonoid yield was fractionated and estimated for flavonoids (total phenol) content. High fat diet rabbits showed significantly increased level of plasma and tissue total cholesterol, triglyceride, free fatty acids, phospholipids, plasma LDL cholesterol and decreased level of plasma HDL cholesterol. Administration of isolated flavonoids high fat diet rabbits showed near to normal (control) level of the above lipid profiles in plasma and tissues. Hence it is concluded that flavonoids possessed antilipidemic activity in high fat diet fed rabbits.¹⁵

The phenol content (mg/g) of studied legume seeds were Phaseolus vulgaris (1.43), Glycine max (1.32), Pisum sativum (0.92), D. biflorus (0.87), Vigna mungo (0.74), V.radiata (0.48) and Lathyrus sativus (0.31). Biological parameters were directly influenced by phenol contents of seeds. Phenol content appeared to be the most significant criteria responsible for susceptibility and persistency of pulse beetles as no adult emergence was recorded in P.vulgaris and G.max.¹⁶

Pharmacological Review of herb Dolichos biflorus

The seeds of D. biflorus have been reported to show antilithiatic, antihepatotoxic and hypolipidemic activity and involved in lowering the level of blood sugar and total cholesterol. Two Ayurvedic preparations, having D. biflorus as an ingredient, have shown their antinephrotoxic and free radical scavenging activity. The present study is aimed to evaluate the antioxidant and free radical scavenging activity of a 70% methanol extract of D. biflorus seeds.⁹

A study was undertaken to evaluate the in vitro antilithiatic activity of soxhlet extract of D.biflorus (Leguminosae) seeds and Satawar (Asparagus racemosus, Liliaceae) roots. The in vitro activity was determined by inhibition of calcium (titermetric analysis) and phosphate (colorimetric analysis) precipitation. Cystone (a marketed product) was used as reference drug for comparison. Extracts of D.biflorus showed activity almost equivalent to cystone but extracts of Asparagus racemosus were not as active as cystone. The combined effect was not as active as individual extracts.¹⁰

Patients were enrolled in the study and randomly assigned into three groups. Group 1st received Kulattha (D.biflorus, Leguminosae), Group 2nd received Varun (Crataeva nurvala, Capparidaceae) and Group 3rd received Placebo. At the end of six months symptomatic improvement and decrease in crystalluria in Group1st and 2nd compared to Group 3rd were noticed. There was no significant reduction in stone size in any of the groups.¹¹

Nephro-protective activity was evaluated in gentamicin induced nephrotoxicity (80 mg/kg/day s.c) in male albino rats, NR-AG-I (containing Crataeva nurvala, Tribulus terrestris, D.biflorus and Shilajeet) and NR-AG-II (C.nurvala, Boerhaavia diffusa, Saccharum officinarum and Butea frondosa) were tested at a dose of 150 mg/kg/day p.o. All the treatments were given for 12days.Urea clearance and microscopical examinations of kidney were performed after the treatment. Gentamicin treatment caused nephrotoxicity as evidenced by significant decrease in urea clearance and was prevented by both formulations. Study of renal microscopy showed necrosis, epithelial loss with granular degeneration and fatty changes in gentamicin treated rats and was reversed by both formulations, but NR-AG-I proved to be better formulation.¹²

Total antioxidant activity¹³

An improved ABTS.+ radical cation decolourisation assay was used to evaluate the antioxidant capacity of D. biflorus the in comparison to trolox standard. ABTS solution was mixed with potassium perasulfate and kept overnight to generate ABTS.+ radical cation. Then 10 l sample solution was mixed with 1 ml ABTS.+ solution and the absorbance was measured at 734 nm. All experiments were repeated 6 times. The Trolox equivalent antioxidant capacity (TEAC) was determined by plotting the percentage inhibition of absorbance as a function of concentration of standard and sample.

In vitro Antioxidant and free radical scavenging activity of methanolic extract of Dolichos biflorous was studied. A positive linear correlation was found between the phenol and DPPH scavenging activity (R² = 0.796). Dolichos biflorous has a potential source of useful natural antioxidants.^{17, 18}

Anti-bacterial activity¹⁴

The antimicrobial activity was tested against crude ethyl acetate, acetone and methanol extracts of Azadirechta. indica, Cassia. angustifolia, Cassia. roseus, D. melanoxylon, D. biflorus, G.sylvestre and J.procumbens. The inoculation of microorganism was prepared from bacterial culture [13]. The inoculums suspension was spread uniformly over the agar plates using spreader, for uniform distribution of bacteria. Subsequently, using a sterile borer, well of 0.5cm diameter was made in the inoculated media in addition to 0.2 ml of each extract was aseptically filled into the well. Later the plates were placed at room temperature for an hour to allow diffusion of extract into the agar. Then the plates were incubated for 24 h at 370C for room temperature. Tetracycline (30 mcg/ml) was used as positive control. The results were recorded by measuring the diameter of inhibition zone at the end of 24-72 h. Zone of inhibition surrounding the discs was measured using a transparent ruler and the diameter was recorded in mm. Results of inhibition zones in the well diffusion assay using crude ethyl acetate, acetone and methanol extracts of A. indica, C. angustifolia, C. roseus , D. melanoxylon , D. biflorus, G.sylvestre and J.procumbens showed significant zone of inhibition (ZOI) against Gram positive bacteria, B. cereus, and Gram negative bacteria, K. pneumonia, A. hydrophila, E. aerogenes, and E. coli of five tested bacterial organisms as compared to the standard antibiotic, Tetracycline (30 mcg/ ml). The highest zone of inhibition was observed in leaf methanol extract of A. indica against E. aerogenes (25 mm), K. pneumoniae (18mm) and E. coli (20 mm), and flower acetone extract of A. indica against E.coli (19 mm), flower methanol extract of C. angustifolia, leaf acetone extract of G. sylvestre against B. cereus (22 mm), respectively and very low zone of inhibition was observed in ethyl acetate, acetone and methanol extract of D. biflorus against A. hydrophila, B. cereus, and K. pneumoniae , E. Aerogenes.

Dolichos biflorus is a non-toxic seed which can be used as a food

Horse gram (Dolichos biflorus L.) seeds were used to conduct animal experiment to evaluate the palatability and toxicity of the food. Thirty days old male wistar rats (Rattus norvegicus) were used for the feeding experiment for 42 days duration. The seed meals mixed (20%) separately with standard rat feed was given to the rats. On the 42 day the animals were sacrificed. Blood from the animals were taken for the comparative analysis and characterization in terms of weight gain, haematological parameters, biochemical analysis and the lipid profile. There was significant gain in body weight in treated rats. The rats that consumed black seed morphoforms showed highest weight gain (177g). The blood parameter Haemoglobin (HB) varied from 10.72% to 13%. Random blood sugar (RBS) was high in brown morphoform fed rats. In liver function test the parameters tested were normal in all treatments. Cream morphoform seed fed rats showed higher value for serum bilirubin (0.4mg %) compared to all others including control. Total protein content was high in black (6.6mg %) seed fed rats. The lipid profile showed that total cholesterol was maximum in black morphoform fed rats (80.66mg/dl) and showed no significant variation among the morphoforms. All the above findings support the non toxic nature of the seed consumption.²⁰

Dolichos biflorous is an effective drug used for weight reduction ²³

Hydro-alcoholic extract of Peper betle and Alcoholic extract of Dolichos biflorous seed in the ratio of 2:3 is effectively used in the weight management in human volunteers. A novel herbal formulation LI10903F, alternatively known as LOWAT was developed based on its ability to inhibit adipogenesis and lipogenesis in 3T3-L1 adipocytes model. The clinical efficacy and tolerability of LI10903F were evaluated in an eight-week, randomized, double-blind, placebo-controlled, clinical trial in 50 human subjects with body mass index (BMI) between 30 and 40 kg/m2 (clinical trial registration number: ISRCTN37381706). Participants were randomly assigned to either a placebo or LI10903F group. Subjects in the LI10903F group received 300 mg of herbal formulation thrice daily, while subjects in the placebo group received 300 mg of placebo capsules thrice daily. All subjects were provided a standard diet (2,000 kcal daily) and participated in a moderate exercise of 30 min walk for five days a week. Additionally, the safety of this herbal formulation was evaluated by a series of acute, sub-acute toxicity and genotoxicity studies in animals and cellular models. After eight weeks of supplementation, statistically significant net reductions in body weight (2.49 kg; p=0.00005) and BMI (0.96 kg/m2; p=0.00004) were observed in the LI10903F group versus placebo group. Additionally, significant increase in serum adiponectin concentration (p=0.0076) and significant decrease in serum ghrelin concentration (p=0.0066) were found in LI10903F group compared to placebo group. Adverse events were mild and were equally distributed between the two groups. Interestingly, LI10903F showed broad spectrum safety in a series of acute, sub-acute toxicity and genotoxicity studies. The results of the current research suggest that LI10903F or LOWAT is well-tolerated, safe and effective for weight management.

Anti-Urolithiatic Activity of Dolichos Biflorus Seeds ²⁴

We have studied aqueous, chloroform, benzene extracts of Dolichos biflorus.Linn and standard drug Cystone for dissolving kidney stones- calcium oxalate by an in-vitro model. To check their potential to dissolve experimentally prepared kidney stones- calcium oxalate by an in-vitro model for Dolichos biflorus seeds and cystone as a standard compound collected from market . Phenolic compound isolated from the benzene and aqueous, flavanoids and steroids from aqueous fraction of the seed. Aqueous fractions showed highest dissolution of stones as compare to others. Aqueous fraction was more effective in dissolving calcium oxalate (48.5±0.022%). Reference standard-formulation Cystone was found to be more effective (53.5±0.02 %) when compared to phenolic and flavanoids fraction.

Dolichos biflorus Seeds reduces Hyperlipidemia ²⁵

The aqueous extract of Dolichos biflorus seeds was tested for in hyperlipidaemic models of wister albino rats. Dolichos biflorus seeds exhibited significant protective activity by reducing lipids. The present study shows the Total Cholesterol Triglceride High Density Lipoprotein Low Density Lipoprotein Low Very Density Lipoprotein were altered due to cholesterol induction. After the Dolichos biflorus seeds extract treatment, the Total Cholesterol Triglceride High Density Lipoprotein Low Density Lipoprotein Low Very Density Lipoprotein were recovered. The present study concludes that the Dolichos biflorus reduces the hyperlipidaemic models of rats.

Phytochemical and Pharmacological Studies of Dolichos biflorus ^{26, 28}

Micromorphology and physicochemical analysis of the seeds of Dolichos biflorus Linn. (Family: Papileonaceae) was studied. Macroscopy, microscopy, physicochemical analysis, preliminary screening and other WHO recommended parameters for standardizations were performed. Seed extract of Dolichos biflorus was investigated for the phytochemical and pharmacological activity . Phytochemical analysis was performed on extract and powder form of the drug. Procedure use for evaluation were Identification of chemical constituent by color reaction, Fluorescence analysis of powder drug, pH (in powder and extract forms), loss on drying, Thin layer chromatography, Infrared spectroscopy, acid and saponification values. In pharmacological studies (diuretic, analgesic and anti-inflammatory activities) were tested on the extract of plant seed. The tests were carried out over albino mice taking different concentration of seed extract. Seeds extract of Dolichos biflorus has exhibited mild analgesic activity, the results were (84.6Â±6.68) at dose 300mg/kg and (92.2Â±6.81) at dose 500mg/kg which were not much significant as compared to reference drug Aspirin (300mg/kg) having result (36.4Â±2.27). While seed extract of Dolichos biflorus exhibited remarkable diuretic activity, the values at 300 mg/kg was (1.33Â±0.13) and at 500 mg/kg were (2.66Â±0.31) which are highly significant as compared to drug Lasix (20mg /kg) having result (2.38Â±0.23). Anti-inflammatory effects of crude extract of Dolichos biflorus obtained at 0.06mg/kg and 01 mg/kg were (26.6Â±2.96) and (36Â±1.67) respectively. While the value for aspirin as standard drug (300mg/kg) were (17.44Â±1.59).This study provides a platform for further investigation for the isolation of active principles responsible for biological activity.

Chemomodulatory Effect of Dolichos biflorus Linn.²⁷

Significant reduction in tumor incidence (up to 33 % ) and tumor multiplicity (up to 61 % ) was observed in Forestomach Papillomagnesis model.

Seed Lectin from Dolichos biflorus (Horse Gram) Exhibit Lipoxygenase Acivity²⁸

Plant–pathogen interactions play a vital role in developing resistance to pests. Dolichos biflorus (horse gram), a leguminous pulse crop of the subtropics, exhibits amazing defence against attack by pests/pathogens. Investigations to locate the possible source of the indomitable pest resistance of D. biflorus, which is the richest source of LOX (lipoxygenase) activity, have led to amolecule that exhibits LOX-like functions. The LOX-like activity associated with the molecule, identified by its structure and stability to be a tetrameric lectin, was found to be unusual. The evidence for the lectin protein with LOX activity has come from (i) MALDI–TOF (matrix-assisted laser-desorption ionization–time-of-flight) MS, (ii) N-terminal sequencing, (iii) partial sequencing of the tryptic fragments of the protein, (iv) amino acid composition, and (v) the presence of an Mn2+ ion. A hydrophobic binding site of the tetrameric lectin, along with the presence of anMn2+ ion, accounts for the observed LOX like activity. This is the first ever report of a protein exhibiting both haemagglutination and LOX-like activity. The two activities are associated with separate loci on the same protein. LOX activity associated with this molecule adds a new dimension to our understanding of lectin functions. This observation has wide implications for the understanding of plant defence mechanisms against pests and the cellular complexity in plant–pathogen interactions that may lead to the design of transgenics with potential to impart pest resistance to other crops.

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Received on 22.05.2015 Modified on 10.06.2015

Res. J. Pharmacology & P’dynamics. 7(2): April- June 2015; Page 103-116

DOI: 10.5958/2321-5836.2015.00021.X

Type of Kidney Stone	Population	Circumstances	Details
Calcium oxalate	80%	when urine is acidic (low pH)	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 an organic molecule found in many vegetables, fruits, and nuts. Calcium from bone may also play a role in kidney stone formation.
Calcium phosphate	2-5%	When urine is alkaline (high pH)
Uric acid	5-10%	When urine is persistently acidic	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	Preventing struvite stones depends on staying infection-free. Diet has not been shown to affect struvite stone formation.
Cystine	7-8%	Rare genetic disorder	Cystine, an amino acid (one of the building blocks of protein), leaks through the kidneys and into the urine to form crystals.