DescriptionAn in-depth report on the causes, diagnosis, treatment, and prevention of kidney stones.
Alternative NamesCalcium Stones; Extracoporeal Shock Wave Lithotripsy; Lithotripsy; Nephrolithiasis; Oxalates; Uric Acid
Kidney stones develop as a result of a complicated interaction of biologic events that are most likely triggered by genetic susceptibility coupled with dietary factors. The process is not completely known.
General Biologic Events Leading to Kidney Stones
The key process in the development of kidney stones is supersaturation.
Different factors may be involved in either reducing urine volume or increasing the levels of the salts.
Deficiencies in Protective Factors. Normally, urine contains protective factors that include magnesium, citrate, pyrophosphate, and various proteins and enzymes. These compounds may protect against stone formation in various ways:
Deficiencies in these protective substances, therefore, cause stones.
Changes in the Acidity of the Urine. Changes in the balance of acid to alkaline in the urine can affect stone precipitation.
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 adhere to the tubes or deficiencies in those that prevent them from sticking.
Causes of Calcium Stones
In general, calcium stones form when there are imbalances of components in the urine that either promote or inhibit formation of the stone. Often, the cause of calcium stones is not known, a condition called idiopathic nephrolithiasis. Increasingly, 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, 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, or due to unknown causes. The following are mechanisms that can lead to hypercalciuria and calcium stones:
Excess Oxalate in the Urine (Hyperoxaluria). Oxalate, also called oxalic acid combines with calcium to form calcium oxalate, which 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.
Secondary hyperoxaluria is usually caused by excessive intake of dietary oxalates (found in a number of common vegetables, fruits, and grains) or by abnormalities in the metabolism of oxalates. Such defects may be due to various factors, such as the following:
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, which can occur because of the following:
High Levels of Uric Acid (Hyperuricosuria). High levels of uric acid in urine are referred to as hyperuricosuria and occur in between 15% to 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 primary agent for removal of excess calcium. It also inhibits the process that turns calcium crystals into stone. Low levels in the urine, known as hypocitraturia, are 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 severe enough to cause stones are unknown. Some causes include the following:
Low Levels of Other Stone-Inhibiting Compounds. In addition to citrate, other substances in urine also prevent calcium from precipitating out or forming calcium stones. Some of these include nephrocalcin-A and uropontin (molecules known as glycoproteins), glycosaminoglycan, magnesium, and pyrophosphate.
Nanobacteria Infection. An interesting focus of investigation is the discovery of extremely tiny infectious agents, termed nanobacteria. (Although their name implies bacteria, it is not even clear if these are living things.) Nanobacteria are able to pass from the blood into urine and coat themselves with mineral deposits that resemble the composition of kidney stones. Cells infected with these agents develop mineral deposits both on the inside and outside. Researchers hypothesize that nanobacteria may form the cores of the kidney stones in many people.
Causes of Uric Acid Stones
Uric acid stones are formed from crystals made from purine, a nitrogen end product of dietary protein. There are usually three conditions observed in patients with uric stones:
A number of conditions may contribute to or cause uric acid stones:
Causes of Struvite Stones
Struvite stones are almost always caused by urinary tract infections due to bacteria that secrete certain enzymes. These enzymes, in turn, raise urine concentrations of the ammonia that composes the crystals forming 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 than 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.