Causes:

The key process in the development of kidney stones is supersaturation.

• The urine carries salts, including calcium oxalate, uric acid, cystine, or xanthine.
• These salts can become extremely concentrated if there is not enough urine, or if unusually high amounts of crystal-forming salts are present.
• When salt concentration levels reach the point at which they no longer dissolve, these salts form crystals.

Different factors may be involved in either reducing urine amount, or increasing the levels of the salts.

Deficiencies in Protective Factors. Normally, urine contains substances that may protect against stone formation, including:

• Magnesium
• Citrate
• Pyrophosphate
• Enzymes

These substances:

• Allow salt in the urine to be at higher-than-normal concentrations without forming crystals
• Prevent crystal formation
• Coat the crystals and prevent them from sticking to the surface of kidney tubes

Not having enough of these protective substances can cause stones.

Changes in the Acidity of the Urine. Changes in the acid balance of the urine can affect stone formation.

• Uric acid and cystine stones mainly form in acidic urine.
• Calcium phosphate and struvite stones increase in alkaline urine.

Causes of Calcium Stones

Often, the cause of calcium stones is not known. The condition is then called idiopathic nephrolithiasis. Research suggests that nearly all stones result from problems in the breakdown and absorption of calcium and oxalate. Genetic factors may play a role in about half of these cases. A number of medical conditions and drugs can also affect digestion and intestinal absorption.

Excess Calcium in the Urine (Hypercalciuria). Hypercalciuria (too much calcium in the urine) is responsible for as much as 70% of calcium-containing stones. A number of conditions may produce hypercalciuria. Many are due to genetic factors, but most cases are due to unknown causes (idiopathic).

The following can lead to hypercalciuria and calcium stones:

• Too much calcium absorption in the intestines: In most of these conditions, genetic factors lead to increased calcium absorption in the intestine.
• Excessive chloride: Chloride has a negative charge, and calcium has a positive one, so they balance each other in the body. Excess chloride may lead to excess calcium.
• Renal calcium leak: In this condition, the does not regulate minerals normally, causing an increase of calcium in the urine.
• Excessive sodium: High urinary levels of sodium result in increased levels of calcium. Certain defects in the kidney tubules transport system, which cause imbalances in sodium and phosphate, can lead to high calcium levels in the urine. A diet high in salt can also produce this effect.

Excess Oxalate in the Urine (Hyperoxaluria). Oxalate is the most common stone-forming compound. Too much oxalate in the urine is responsible for up to 60% of calcium stones and is a more common cause of stones than too much calcium in the urine.

Hyperoxaluria can be either primary or secondary.

• Primary hyperoxaluria is an inherited disorder in which too much oxalate in the urine is the main problem.
• Secondary hyperoxaluria results from specific conditions that cause high levels of urinary oxalate.

Secondary hyperoxaluria is usually caused by too much dietary oxalates (found in a number of common vegetables, fruits, and grains) or by problems in the body's breakdown of oxalates. Such defects may be due to various factors:

• Severe vitamin B6 deficiencies (usually due to genetic disorders)
• Deficiencies in Oxalobacter formigenes, an intestinal bacteria that breaks down oxalate
• Short bowel syndrome, a condition that generally results from removal of portions of the small intestines. It causes an inability to properly absorb fat and nutrients. Calcium may bind to the unabsorbed fat instead of the oxalates, which causes a buildup of oxalate
• Androgens (male hormones)

Female hormones (estrogens) actually lower the risk of hyperoxaluria. Estrogen may help prevent the formation of calcium oxalate stones by keeping urine alkaline, and raising protective citrate levels.

Patients who undergo the most common gastric type of bypass surgery, the Roux-en-Y, may be at increased risk for calcium oxalate kidney stones, beginning 6 months after surgery. These patients develop hyperoxaluria, and the condition is common 12 months after surgery.

Excessive Calcium in the Bloodstream (Hypercalcemia). Hypercalcemia generally occurs when bones break down and release too much calcium into the bloodstream. This is a process called resorption. It can occur from a number of different diseases and events:

• Hyperparathyroidism: Overactive parathyroid glands cause about 5% of calcium stones. People with this disorder have at least a 20% chance of developing kidney stones. Women are more likely to have this disorder than men.
• Immobilization: Lack of movement can lead to kidney stones.
• Renal tubular acidosis: This disorder causes an acidic and alkaline imbalance. Renal tubular acidosis not only increases calcium levels in the bloodstream, but it also reduces protective citrate levels.

Hyperuricosuria is a condition in which there are high levels of uric acid in urine. It occurs in 15 - 20% of people (mostly men) with calcium oxalate stones. Urate, the salt formed from uric acid, creates the center of a crystal (nidus), around which calcium oxalate crystals form and grow. Such stones tend to be severe and recurrent. They appear to be strongly related to a high intake of protein. (Hyperuricosuria also plays a major role in some uric acid stones.)

Low Urine Levels of Citrate (Hypocitraturia). Citrate is the main substance in the body that is responsible for removing excess calcium. It also blocks the process that turns calcium crystals into stones. Low levels of citrate in the urine is a significant risk factor for calcium stones. Hypocitraturia also increases the risk for uric acid stones. This condition most likely contributes to about a third of all kidney stones.

Many conditions can reduce citrate levels. Some causes include:

• Renal tubular acidosis
• Potassium or magnesium deficiency
• Urinary tract infection
• Kidney failure
• Chronic diarrhea

Often, however, the cause of hypocitraturia-related stones is unknown.

Low Levels of Other Stone-Blocking Compounds. Several other compounds in the urine, including magnesium and pyrophosphate, also prevent the formation of calcium stones. If any of these compounds are lacking, stones may develop.

Causes of Uric Acid Stones

Human body tissues, and certain foods, substances called purines. Purine-containing foods include dried beans, peas, and liver. When the body breaks down purines, it produces uric acid. The presence of a certain level of uric acid in the body is normal, but excess uric acid can lead to stones.

The following conditions are usually seen in patients with uric acid stones:

• Too much uric acid in the urine for a long period (the most important cause of uric acid stones)
• Lower than normal amounts of urine produced
• Hyperuricosuria, a metabolic disorder that leads to high levels of uric acid in the urine

Note: Hyperuricosuria can also trigger calcium stones. Therefore, a combination of calcium and uric acid stones may be present in patients with hyperuricosuria.

A number of conditions and other factors may contribute to, or cause, uric acid stones:

• Gout: Uric acid and other kidney stones develop in up to 25% of patients with primary gout, a painful form of arthritis that occurs when uric acid in the blood forms crystals in one or more joints.
• Diabetes: People with type 2 diabetes have highly acidic urine that can lead to kidney stones, particularly uric acid stones.
• Insulin resistance: People with insulin resistance have an increased risk for uric acid stones. The reason is unknown but may be related to the transport of certain salts through the kidneys. This transport changes in patients with insulin resistance.
• Kidney abnormalities: Kidney problems that reduce the production of ammonia, particularly in people with diabetes or insulin resistance, may lead to uric acid stones.
• Genetic factors: Inherited factors can increase a person's risk for uric acid stones.
• Hypocitraturia: Hypocitraturia is a low amount of citrate in the urine.
• Diet: Eating too much animal protein increases the risk of forming uric acid stones.

Other risk factors include:

• Certain medications (chemotherapy drugs, diuretics, and salicylates)
• Binge drinking
• Not eating for long periods of time (fasting)
• Lead poisoning
• Treatment of blood cancers (leukemia, multiple myeloma, and lymphomas)
• Some rare types of anemia (low levels of red blood cells in the blood)
• Chronic diarrhea

Causes of Struvite Stones

Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes. These enzymes raise the concentration of ammonia in the urine. Ammonia makes up the crystals that form struvite stones. The stone-promoting bacteria are usually Proteus, but may also include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci. Women are twice as likely to have struvite stones as men.

Causes of Other Stones

Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Causes of Cystine Stones. Cystine stones develop from genetic defects that cause abnormal transport of amino acids in the kidney and gastrointestinal system, leading to a build-up of cystine, one of these amino acids. Researchers have identified two genes responsible for this condition: SLC3A1 and CLC7A9.

Causes of Xanthine Stones. In some cases, xanthine stones may develop in patients being treated with allopurinol for gout.