• Highlights
• Introduction
• Causes
• Risk Factors
• Symptoms
• Diagnosis
• Treatment
• Medications
• Other Treatments
• Complications
• Prevention
• Resources
• References

Kidney stones

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of kidney stones.

Alternative Names

Calcium stones; Nephrolithiasis

Causes

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

• Salts, including calcium oxalate, uric acid, cystine, or xanthine, are carried in urine.
• These salts can become extremely concentrated if the volume of urine is significantly reduced or if abnormally high amounts of crystal-forming salts are present.
• When concentration levels reach the point at which the salts no longer dissolve, the salts form crystals.

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

Deficiencies in Protective Factors. Normally, urine contains substances (magnesium, citrate, pyrophosphate, various proteins, enzymes) that may protect against stone formation. 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

Deficiencies in these protective substances can cause stones.

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

• Uric acid and cystine stones thrive in acidic urine.
• Calcium phosphate and struvite stones thrive in alkaline.

Factors that Bind Crystals to the Kidney Tubules. Researchers are studying the cells lining the kidney tubules in order to understand how and why early crystals bind to the tubes long enough to form stones. Under investigation are elevated levels of substances that either cause crystals to stick to the tubes or deficiencies in those that prevent them from sticking.

Causes of Calcium Stones

In general, calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of calcium stones is not known. This condition is called idiopathic nephrolithiasis. Research suggests that abnormalities in metabolism (i.e., digestion and intestinal absorption of calcium or oxalate) are responsible for nearly all stones. 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). About 70% of calcium-containing stones are caused by hypercalciuria , a condition in which there is too much calcium in the urine. A number of conditions may produce hypercalciuria. Many are due to genetic factors, but most cases are idiopathic (due to unknown causes).

The following can lead to hypercalciuria and calcium stones.

• Too much calcium absorption in the intestines. In most of these conditions, genetic factors conspire to increase calcium absorption in the intestine. Researchers are investigating a possible defective gene that regulates calcitriol, a form of vitamin D, which, in excess levels, may increase intestinal absorption of calcium.
• Excessive chloride. Chloride has a negative charge and calcium a positive one, so they are often used by the body to balance each other. Excess chloride may lead to excess calcium. A gene known as CLCN5, which regulates chloride in the urine, is defective in many patients with calcium stones.
• Renal calcium leak. This is a condition in which the filtering processes in the kidney fail, causing an increase of calcium in the urine.
• Excessive sodium. High urinary levels of sodium result in increased levels of calcium. Defects in the kidney tubules transport system that cause imbalances in sodium and phosphate can lead to high calcium in the urine. A high salt diet can also produce this effect.

Excess Oxalate in the Urine (Hyperoxaluria). Oxalate is the most common stone-forming compound. Excessive oxalate in the urine (hyperoxaluria) is responsible for about 30% of calcium stones and is a more common cause of stones than too much calcium in the urine.

Hyperoxaluria is defined as either primary or secondary.

• Primary hyperoxaluria is an inherited disorder in which excess oxalate in the urine is the main problem.
• Secondary hyperoxaluria is caused by specific conditions that result in excess urinary oxalate.

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

• Severe vitamin B6 deficiencies (usually due to genetic disorders)
• Deficiencies in Oxalobacter formigene, an intestinal bacteria that degrades oxalate
• Short bowel syndrome, a condition that makes the intestines unable to properly absorb fat and nutrients; calcium may bind to unabsorbed fat instead of oxalates, which causes excess oxalate
• Androgens (male hormones)

Female hormones (estrogens) are linked to a lower risk. Estrogen may help prevent the formation of calcium stones by keeping urine alkaline and raising protective citrate levels.

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, a disorder that causes acid and alkaline imbalance. It not only increases calcium levels in the bloodstream, it also reduces citrate levels.

High Levels of Uric Acid (Hyperuricosuria). High levels of uric acid in urine are referred to as hyperuricosuria and occur in between 15 - 20% of people (mostly men) with calcium oxalate stones. (Hyperuricosuria is not related to the acidity of the urine itself.) In such cases, urate (the salt formed from uric acid) creates a crystal nidus (the nucleus of a crystal), around which calcium oxalate crystals form and grow. Such stones tend to be severe and recurrent and 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 for removing excess calcium. It also blocks the process that turns calcium crystals into stone. Low levels of citrate in the urine ( hypocitraturia) is a significant risk factor for calcium stones. In addition, 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, but often the causes of hypocitraturia-related stones are unknown. Some causes include:

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

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

Nanobacteria Infection. Nanobacteria are tiny infectious organisms that can pass from the blood into urine. They coat themselves with mineral deposits that resemble the composition of kidney stones. Cells infected with these bacteria develop mineral deposits on the inside and outside. Researchers believe that nanobacteria may form the cores of the kidney stones in many people.

Causes of Uric Acid Stones

Uric acid is produced when substances in the body called purines break down. Purines are found in human body tissue and certain foods such as dried beans, peas, and liver, and certain alcoholic drinks.

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

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

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 may contribute to or cause uric acid stones.

• Gout (Uric acid and other kidney stones develop in 10 -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. New research has shown that people with type 2 diabetes have highly acidic urine that can lead to kidney stones, particularly uric acid stones. The findings are published in the May 2006 Journal of the American Society of Nephrology .
• Insulin resistance
• Possibly kidney abnormalities that reduces ammonia productions, particularly in people with diabetes or insulin resistance
• Genetic factors
• Hypocitraturia, a low amount of citrate in the urine
• Diets overly rich in animal proteins (purines)
• Certain medications (chemotherapy agents, diuretics, and salicylates)
• Binge drinking
• Not eating for long periods of time (fasting)
• Lead poisoning
• Blood cancers (leukemia, multiple myeloma, and lymphomas)
• Some rare types of anemia
• Chronic diarrhea

Causes of Struvite Stones

Struvite stones are almost always caused by urinary tract infections due to bacteria that secrete certain enzymes. These enzymes raise urine concentrations of the ammonia that 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.

• Review Date: 5/22/2006
• Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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