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Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a
crystallopathy Crystallopathy is a harmful state or disease associated with the formation and aggregation of crystals in tissues or cavities, or in other words, a heterogeneous group of diseases caused by intrinsic or environmental microparticles or crystals, pr ...
where a solid piece of material (kidney stone) develops in the
urinary tract The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, c ...
. Kidney stones typically form in the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
and leave the body in the urine stream. A small stone may pass without causing symptoms. If a stone grows to more than , it can cause blockage of the
ureter The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...
, resulting in sharp and severe pain in the lower back or abdomen. A stone may also result in
blood in the urine Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
, vomiting, or painful urination. About half of people who have had a kidney stone will have another within ten years. Most stones form by a combination of
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
and environmental factors. Risk factors include high urine calcium levels,
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
, certain foods, some medications,
calcium supplement Calcium supplements are salts of calcium used in a number of conditions. Supplementation is generally only required when there is not enough calcium in the diet. By mouth they are used to treat and prevent low blood calcium, osteoporosis, and ...
s,
hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...
,
gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...
and not drinking enough fluids. Stones form in the kidney when
mineral In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. (2 ...
s in
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...
are at high concentration. The
diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
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 The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...
), cystolithiasis (in the
bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
), or by what they are made of ( calcium oxalate,
uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ...
, struvite,
cystine Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mec ...
). 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 Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...
,
citrate Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the ...
, or
allopurinol Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...
may be taken. It is recommended that soft drinks containing
phosphoric acid Phosphoric acid (orthophosphoric acid, monophosphoric acid or phosphoric(V) acid) is a colorless, odorless phosphorus-containing solid, and inorganic compound with the chemical formula . It is commonly encountered as an 85% aqueous solution, w ...
(typically
cola Cola is a carbonated soft drink flavored with vanilla, cinnamon, citrus oils and other flavorings. Cola became popular worldwide after the American pharmacist John Stith Pemberton invented Coca-Cola, a trademarked brand, in 1886, which was imi ...
s) be avoided. When a stone causes no symptoms, no treatment is needed; otherwise,
pain control Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals pr ...
is usually the first measure, using medications such as nonsteroidal anti-inflammatory drugs or
opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
s. Larger stones may be helped to pass with the medication
tamsulosin Tamsulosin, sold under the brand name Flomax among others, is a medication used to treat symptomatic benign prostatic hyperplasia (BPH) and chronic prostatitis and to help with the passage of kidney stones. The evidence for benefit with a ki ...
or may require procedures such as
extracorporeal shock wave lithotripsy Extracorporeal shockwave therapy (ESWT) is a non-invasive, out-patient alternative to surgery for those with many joint and tendon disorders. ESWT sends acoustic shock waves into bone or soft tissue, in effect reinjuring the area on a cellular l ...
,
ureteroscopy Ureteroscopy is an examination of the upper urinary tract, usually performed with a ureteroscope that is passed through the urethra and the bladder, and then directly into the ureter. The procedure is useful in the diagnosis and treatment of diso ...
, or
percutaneous nephrolithotomy Percutaneous nephrolithotomy (PCNL) is a minimally-invasive procedure to remove stones from the kidney by a small puncture wound (up to about 1 cm) through the skin. It is most suitable to remove stones of more than 2 cm in size and wh ...
. 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 The Western world, also known as the West, primarily refers to the various nations and states in the regions of Europe, North America, and Oceania.
since the 1970s. Generally, more men are affected than women. Kidney stones have affected humans throughout history with descriptions of surgery to remove them dating from as early as 600 BC.


Signs and symptoms

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 Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
, restlessness,
hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
, sweating, nausea, and vomiting. It typically comes in waves lasting 20 to 60 minutes caused by
peristaltic Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, which ...
contractions of the ureter as it attempts to expel the stone. The
embryological Embryology (from Greek ἔμβρυον, ''embryon'', "the unborn, embryo"; and -λογία, ''-logia'') is the branch of animal biology that studies the prenatal development of gametes (sex cells), fertilization, and development of embryos and ...
link between the urinary tract, the
genital system The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pheromones are als ...
, 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 In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
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 Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
,
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...
, sugars including honey, refined sugars, fructose and
high fructose corn syrup High-fructose corn syrup (HFCS), also known as glucose–fructose, isoglucose and glucose–fructose syrup, is a sweetener made from corn starch. As in the production of conventional corn syrup, the starch is broken down into glucose by enzy ...
, and excessive consumption of fruit juices may increase the risk of kidney stone formation due to increased
uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ...
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 Distal renal tubular acidosis (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the distal tubule and cortical collecting duct of the di ...
,
Dent's disease Dent's disease (or Dent disease) is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, excess calcium in the urin ...
,
hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...
, primary
hyperoxaluria Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. It is sometimes called Bird's disease, after Golding Bird, who first described the condition. Causes Hyperoxalur ...
, or
medullary sponge kidney Medullary sponge kidney is a congenital disorder of the kidneys characterized by cystic dilatation of the collecting tubules in one or both kidneys. Individuals with medullary sponge kidney are at increased risk for kidney stones and urinary trac ...
. 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

Calcium 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 Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
as a dietary supplement have a higher risk of developing kidney stones. In the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...
, kidney stone formation was used as an indicator of excess calcium intake by the
Reference Daily Intake The Reference Daily Intake (RDI) used in nutrition labeling on food and dietary supplement products in the U.S. and Canada is the daily intake level of a nutrient that is considered to be sufficient to meet the requirements of 97–98% of healt ...
committee for calcium in adults. In the early 1990s, a study conducted for the
Women's Health Initiative The Women's Health Initiative (WHI) was a series of clinical studies initiated by the U.S. National Institutes of Health (NIH) in 1991, to address major health issues causing morbidity and mortality in postmenopausal women. It consisted of three ...
in the US found that postmenopausal women who consumed 1000 mg of supplemental calcium and 400 
international unit In pharmacology, the international unit (IU) is a unit of measurement for the effect, not mass of a substance; the variance is based on the biological activity or effect, for the purpose of easier comparison across similar ''forms'' of substan ...
s of
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
per day for seven years had a 17% higher risk of developing kidney stones than subjects taking a
placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...
. The
Nurses' Health Study The Nurses Health Study is a series of prospective studies that examine epidemiology and the long-term effects of nutrition, hormones, environment, and nurses' work-life on health and disease development. The studies have been among the largest in ...
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 Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosph ...
appears to reduce the risk of stone formation because potassium promotes the urinary excretion of
citrate Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the ...
, 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 acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s (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 Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) ...
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


Supersaturation of urine

When the urine becomes supersaturated (when the urine
solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
contains more
solutes In chemistry, a solution is a special type of homogeneous mixture composed of two or more substances. In such a mixture, a solute is a substance dissolved in another substance, known as a solvent. If the attractive forces between the solvent ...
than it can hold in
solution Solution may refer to: * Solution (chemistry), a mixture where one substance is dissolved in another * Solution (equation), in mathematics ** Numerical solution, in numerical analysis, approximate solutions within specified error bounds * Soluti ...
) 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 The renal medulla is the innermost part of the kidney. The renal medulla is split up into a number of sections, known as the renal pyramids. Blood enters into the kidney via the renal artery, which then splits up to form the segmental arteries whi ...
, 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 In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solub ...
of
uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ...
to less than 8 mg/100 mL. The formation of uric-acid stones requires a combination of
hyperuricosuria Hyperuricosuria is a medical term referring to the presence of excessive amounts of uric acid in the urine. For men this is at a rate greater than 800 mg/day, and for women, 750 mg/day. Notable direct causes of hyperuricosuria are dissol ...
(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 Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mec ...
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 Crystalluria refers to crystals found in the urine when performing a urine test. Crystalluria is considered often as a benign condition and as one of the side effects of sulfonamides and penicillins. The main reason for the identification of urin ...
, 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 The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in ele ...
, 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 ''Proteus mirabilis'' is a Gram-negative, facultatively anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus'' infections in humans. It is widely distributed in soil and ...
'' can produce the enzyme
urease Ureases (), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-contai ...
, 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 Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands are ...
agents, such as citrate, that inhibit the nucleation, growth, and aggregation of calcium-containing crystals. Other endogenous inhibitors include
calgranulin Calgranulin is an S100 calcium-binding protein that is expressed in multiple cell types, including renal epithelial cells and neutrophils. The proteins S100A8 and S100A9 form a heterodimer called calprotectin. Human genes * '' S100A8'' (calgr ...
(an S-100 calcium-binding protein),
Tamm–Horsfall protein Uromodulin (UMOD), also known as Tamm–Horsfall protein (THP), is a Zona pellucida-like domain-containing glycoprotein that in humans is encoded by the ''UMOD'' gene. Uromodulin is the most abundant protein excreted in ordinary urine. Gene T ...
,
glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...
s, uropontin (a form of
osteopontin Osteopontin (OPN), also known as bone /sialoprotein I (BSP-1 or BNSP), early T-lymphocyte activation (ETA-1), secreted phosphoprotein 1 (SPP1), 2ar and Rickettsia resistance (Ric), is a protein that in humans is encoded by the ''SPP1'' gene (secr ...
), nephrocalcin (an acidic glycoprotein), pro
thrombin Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...
F1 peptide, and
bikunin Protein AMBP is a protein that in humans is encoded by the ''AMBP'' gene. Interactions Alpha-1-microglobulin/bikunin precursor has been shown to interact with CD79A. See also * Inter-alpha-trypsin inhibitor * Alpha-1-microglobulin Refere ...
(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. Sufficient dietary intake of
magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...
and
citrate Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the ...
inhibits the formation of calcium oxalate and calcium phosphate stones; in addition, magnesium and citrate operate synergistically to inhibit kidney stones. The efficacy of magnesium in subduing stone formation and growth is dose-dependent.


Hypocitraturia

Hypocitraturia or low urinary-citrate excretion (variably defined as less than 320 mg/day) can be a contributing cause of kidney stones in up to 2/3 of cases. The protective role of citrate is linked to several mechanisms; citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. Therapy with
potassium citrate Potassium citrate (also known as tripotassium citrate) is a potassium salt of citric acid with the molecular formula K3C6H5O7. It is a white, hygroscopic crystalline powder. It is odorless with a saline taste. It contains 38.28% potassium by mass ...
is commonly prescribed in clinical practice to increase urinary citrate and to reduce stone formation rates.
Alkali citrate Alkali citrate (also known as alkaline citrate) is an inhibitor of kidney stones. It is used to increase urine citrate levels - this prevents calcium oxalate stones by binding to calcium and inhibiting its binding to oxalate. It is also used to in ...
is also used to increase urine citrate levels. It can be prescribed or found over-the-counter in pill, liquid or powder form.


Diagnosis

Diagnosis of kidney stones is made on the basis of information obtained from the history, physical examination, urinalysis, and
radiographic Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical radiography ("diagnostic" and "therapeut ...
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
radiodense Radiodensity (or radiopacity) is opacity to the radio wave and X-ray portion of the electromagnetic spectrum: that is, the relative inability of those kinds of electromagnetic radiation to pass through a particular material. Radiolucency or hypod ...
, and they can often be detected by a traditional radiograph of the abdomen that includes the
kidneys, ureters, and bladder An abdominal x-ray is an Projectional radiography, x-ray of the abdomen. It is sometimes abbreviated to AXR, or kidneys, ureters, and bladder, KUB (for kidneys, ureters, and urinary bladder). Indications In children, abdominal x-ray is indicated ...
(KUB film). KUB radiograph, although useful in monitoring size of stone or passage of stone in stone formers, might not be useful in the acute setting due to low sensitivity. Some 60% of all renal stones are radiopaque. In general, calcium phosphate stones have the greatest density, followed by calcium oxalate and magnesium ammonium phosphate stones. Cystine calculi are only faintly
radiodense Radiodensity (or radiopacity) is opacity to the radio wave and X-ray portion of the electromagnetic spectrum: that is, the relative inability of those kinds of electromagnetic radiation to pass through a particular material. Radiolucency or hypod ...
, while
uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ...
stones are usually entirely
radiolucent Radiodensity (or radiopacity) is opacity to the radio wave and X-ray portion of the electromagnetic spectrum: that is, the relative inability of those kinds of electromagnetic radiation to pass through a particular material. Radiolucency or hypod ...
. In people with a history of stones, those who are less than 50 years of age and are presenting with the symptoms of stones without any concerning signs do not require helical CT scan imaging. A CT scan is also not typically recommended in children. Otherwise a noncontrast helical CT scan with sections is the diagnostic method to use to detect kidney stones and confirm the diagnosis of kidney stone disease. Near all stones are detectable on CT scans with the exception of those composed of certain drug residues in the urine, such as from
indinavir Indinavir (IDV; trade name Crixivan, made by Merck) is a protease inhibitor used as a component of highly active antiretroviral therapy to treat HIV/AIDS. It is soluble white powder administered orally in combination with other antiviral drugs. ...
. Where a CT scan is unavailable, an
intravenous pyelogram Pyelogram (or pyelography or urography) is a form of imaging of the renal pelvis and ureter. Types include: * Intravenous pyelogram – In which a contrast solution is introduced through a vein into the circulatory system. * Retrograde pyelogram ...
may be performed to help confirm the diagnosis of urolithiasis. This involves intravenous injection of a
contrast agent A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radiop ...
followed by a KUB film.
Urolith Bladder stones or uroliths are a common occurrence in animals, especially in domestic animals such as dogs and cats. Occurrence in other species, including tortoises, has been reported as well. The stones form in the urinary bladder in varying s ...
s 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 Pyelogram (or pyelography or urography) is a form of imaging of the renal pelvis and ureter. Types include: * Intravenous pyelogram – In which a contrast solution is introduced through a vein into the circulatory system. * 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).
Renal ultrasonography Renal ultrasonography (Renal US) is the examination of one or both kidneys using medical ultrasound. Ultrasonography of the kidneys is essential in the diagnosis and management of kidney-related diseases. The kidneys are easily examined, and most ...
can sometimes be useful, because it gives details about the presence of
hydronephrosis Hydronephrosis describes hydrostatic dilation of the renal pelvis and calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dilation of t ...
, suggesting that the stone is blocking the outflow of urine. Radiolucent stones, which do not appear on KUB, 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 in 2009 was not 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) and other serious disorders that could be causing the symptoms. On the contrary, a 2014 study suggested that ultrasonography should be used as the initial diagnostic imaging test, with further imaging studies be performed at the discretion of the physician on the basis of clinical judgment, and using
ultrasonography Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...
rather than CT as an initial diagnostic test results in less radiation exposure and equally good outcome. File:Kidney stones abdominal X-ray.jpg, Bilateral kidney stones can be seen on this KUB radiograph. There are
phlebolith A phlebolith is a small local, usually rounded, calcification within a vein. These are very common in the veins of the lower part of the pelvis, and they are generally of no clinical importance. When located in the pelvis they are sometimes difficu ...
s in the pelvis, which can be misinterpreted as
bladder stone A bladder stone is a stone found in the urinary bladder. Signs and symptoms Bladder stones are small mineral deposits that can form in the bladder. In most cases bladder stones develop when the urine becomes very concentrated or when one is ...
s. File:3mmstone.png, Axial CT scan of abdomen without contrast, showing a 3-mm stone (marked by an arrow) in the left proximal
ureter The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...
File:Ultrasonography of renal stone located at the pyeloureteric junction.jpg, Renal ultrasonograph of a stone located at the pyeloureteric junction with accompanying hydronephrosis. File:CT measurement of kidney stone in soft tissue and bone window.jpg, Measurement of a 5.6 mm large kidney stone in soft tissue versus skeletal CT window.


Laboratory examination

Laboratory investigations typically carried out include * microscopic examination of the urine, which may show
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s, bacteria, leukocytes,
urinary cast Urinary casts are microscopic cylindrical structures produced by the kidney and present in the urine in certain disease states. They form in the distal convoluted tubule and collecting ducts of nephrons, then dislodge and pass into the urine, wher ...
s, 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 A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and pl ...
, looking for
neutrophilia Neutrophilia (also called neutrophil leukocytosis or occasionally neutrocytosis) is leukocytosis of neutrophils, that is, a high number of neutrophils in the blood. Because neutrophils are the main type of granulocytes, mentions of granulocytosi ...
(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 levels ( hypercalcemia); * 24 hour urine collection to measure total daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate, and
phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...
; * collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple
tea strainer A tea strainer is a type of strainer that is placed over or in a teacup to catch loose tea leaves. When tea is brewed in the traditional manner in a teapot, the tea leaves are not contained in teabags; rather, they are freely suspended in ...
) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.


Composition


Calcium-containing stones

By far, 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 The term calcium phosphate refers to a family of materials and minerals containing calcium ions (Ca2+) together with inorganic phosphate anions. Some so-called calcium phosphates contain oxide and hydroxide as well. Calcium phosphates are whi ...
in the form of apatite or
brushite Brushite is a phosphate mineral with the chemical formula . Crystals of the pure compound belong to the monoclinic space group C2/c and are colorless.precipitation In meteorology, precipitation is any product of the condensation of atmospheric water vapor that falls under gravitational pull from clouds. The main forms of precipitation include drizzle, rain, sleet, snow, ice pellets, graupel and hail. ...
of oxalate crystals in the urine, such as
primary hyperoxaluria Primary hyperoxaluria is a rare condition (autosomal recessive), resulting in increased excretion of oxalate (up to 600 mg a day from normal 50 mg a day), with oxalate stones being common. Signs and symptoms Primary hyperoxaluria is an ...
, are associated with the development of calcium oxalate stones. The formation of calcium phosphate stones is associated with conditions such as
hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...
and renal tubular acidosis. Oxaluria is increased in patients with certain gastrointestinal disorders including inflammatory bowel disease such as Crohn's disease or in 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 that usually presents in childhood. Calcium oxalate crystals can come in two varieties. Calcium oxalate monohydrate can appear as 'dumbbells' or as long ovals that resemble the individual posts in a picket fence. Calcium oxalate dihydrate have a tetragonal “envelope” appearance.


Struvite stones

About 10–15% of urinary calculi are composed of struvite (
ammonium magnesium phosphate Struvite (magnesium ammonium phosphate) is a phosphate mineral with formula: NH4MgPO4·6H2O. Struvite crystallizes in the orthorhombic system as white to yellowish or brownish-white pyramidal crystals or in platy mica-like forms. It is a soft m ...
, NH4MgPO4·6H2O). Struvite stones (also known as "infection stones,"
urease Ureases (), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-contai ...
, or triple-phosphate stones) form most often in the presence of infection by urea-splitting
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
. Using the enzyme urease, these organisms
metabolize Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...
into
ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wa ...
and
carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
. This alkalinizes the urine, resulting in favorable conditions for the formation of struvite stones. ''
Proteus mirabilis ''Proteus mirabilis'' is a Gram-negative, facultatively anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus'' infections in humans. It is widely distributed in soil and ...
'', ''
Proteus vulgaris ''Proteus vulgaris'' is a rod-shaped, nitrate-reducing, indole-positive and catalase-positive, hydrogen sulfide-producing, Gram-negative bacterium that inhabits the intestinal tracts of humans and animals. It can be found in soil, water, and ...
'', and '' Morganella morganii'' are the most common organisms isolated; less common organisms include ''
Ureaplasma urealyticum ''Ureaplasma urealyticum'' is a bacterium belonging to the genus ''Ureaplasma'' and the family Mycoplasmataceae in the order Mycoplasmatales. This family consists of the genera ''Mycoplasma'' and ''Ureaplasma''. Its type strain is T960. There are ...
'' and some species of '' Providencia'', ''
Klebsiella ''Klebsiella'' is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. ''Klebsiella'' species are found everywhere in nature. This is thought to be due to distinct sublineages developi ...
'', ''
Serratia ''Serratia'' is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the family Yersiniaceae. According to the List of Prokaryotic names with Standing Nomenclature (LPSN), there are currently 19 species of ''Serratia'' that a ...
'', and ''
Enterobacter ''Enterobacter'' is a genus of common Gram-negative, facultatively anaerobic, rod-shaped, non-spore-forming bacteria of the family Enterobacteriaceae. It is the type genus of the order Enterobacterales. Several strains of these bacteria are ...
''. These infection stones are commonly observed in people who have factors that predispose them to
urinary tract infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...
s, such as those with
spinal cord injury A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cor ...
and other forms of
neurogenic bladder Neurogenic bladder dysfunction, or neurogenic bladder, refers to urinary bladder problems due to disease or injury of the central nervous system or peripheral nerves involved in the control of urination. There are multiple types of neurogenic bladde ...
,
ileal conduit urinary diversion An ileal conduit urinary diversion is one of various surgical techniques for urinary diversion. It has sometimes been referred to as the Bricker ileal conduit after its inventor, Eugene M. Bricker. It is a form of incontinent urostomy, and was dev ...
,
vesicoureteral reflux Vesicoureteral reflux (VUR), also known as vesicoureteric reflux, is a condition in which urine flows retrograde, or backward, from the bladder into one or both ureters and then to the renal calyx or kidneys. Urine normally travels in one directio ...
, and obstructive uropathies. They are also commonly seen in people with underlying metabolic disorders, such as
idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. From Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approximately "a disease of its own kin ...
hypercalciuria Hypercalciuria is the condition of elevated calcium in the urine. Chronic hypercalciuria may lead to impairment of renal function, nephrocalcinosis, and chronic kidney disease. Patients with hypercalciuria have kidneys that put out higher levels ...
,
hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...
, and
gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...
. 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 a '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 Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
, may produce uric acid stones. They also may form in association with conditions that cause
hyperuricosuria Hyperuricosuria is a medical term referring to the presence of excessive amounts of uric acid in the urine. For men this is at a rate greater than 800 mg/day, and for women, 750 mg/day. Notable direct causes of hyperuricosuria are dissol ...
(an excessive amount of uric acid in the urine) with or without
hyperuricemia Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7&nbs ...
(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 Radiodensity (or radiopacity) is opacity to the radio wave and X-ray portion of the electromagnetic spectrum: that is, the relative inability of those kinds of electromagnetic radiation to pass through a particular material. Radiolucency or hypod ...
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), people with inflammatory bowel disease ( Crohn's disease,
ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...
) tend to have hyperoxaluria and form oxalate stones. They 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.


Other types

People with certain rare
inborn errors of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substra ...
have a propensity to accumulate crystal-forming substances in their urine. For example, those with
cystinuria Cystinuria is an inherited autosomal recessive disease characterized by high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidneys, ureters, and bladder. It is a type of aminoaciduri ...
,
cystinosis Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine. It is a genetic disorder that follows an autosomal recessive inheritance pattern. It is a rare autosom ...
, and
Fanconi syndrome Fanconi syndrome or Fanconi's syndrome (, ) is a syndrome of inadequate reabsorption in the proximal renal tubules of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity (for example, from tox ...
may form stones composed of
cystine Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mec ...
. Cystine stone formation can be treated with urine alkalinization and dietary protein restriction. People affected by
xanthinuria Xanthinuria, also known as xanthine oxidase deficiency, is a rare genetic disorder causing the accumulation of xanthine. It is caused by a deficiency of the enzyme xanthine oxidase. It was first formally characterized in 1954. Presentation Suff ...
often produce stones composed of
xanthine Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine ...
. People affected by adenine phosphoribosyltransferase deficiency may produce 2,8-dihydroxyadenine stones, alkaptonurics produce
homogentisic acid Homogentisic acid (2,5-dihydroxyphenylacetic acid) is a phenolic acid usually found in ''Arbutus unedo'' (strawberry-tree) honey. It is also present in the bacterial plant pathogen ''Xanthomonas campestris'' pv. ''phaseoli'' as well as in the ye ...
stones, and iminoglycinurics produce stones of
glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
, proline, and
hydroxyproline (2''S'',4''R'')-4-Hydroxyproline, or L-hydroxyproline ( C5 H9 O3 N), is an amino acid, abbreviated as Hyp or O, ''e.g.'', in Protein Data Bank. Structure and discovery In 1902, Hermann Emil Fischer isolated hydroxyproline from hydrolyzed gelati ...
. 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 Indinavir (IDV; trade name Crixivan, made by Merck) is a protease inhibitor used as a component of highly active antiretroviral therapy to treat HIV/AIDS. It is soluble white powder administered orally in combination with other antiviral drugs. ...
, sulfadiazine, and
triamterene Triamterene (trade name Dyrenium among others) is a potassium-sparing diuretic often used in combination with thiazide diuretics for the treatment of high blood pressure or swelling. The combination with hydrochlorothiazide, is known as hydro ...
.


Location

Urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder. Nephrolithiasis refers to the presence of such stones in the kidneys. Calyceal calculi are aggregations in either the minor or
major calyx The renal calyces are chambers of the kidney through which urine passes. The minor calyces surround the apex of the renal pyramids. Urine formed in the kidney passes through a renal papilla at the apex into the minor calyx; two or three minor ca ...
, 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
bladder stone A bladder stone is a stone found in the urinary bladder. Signs and symptoms Bladder stones are small mineral deposits that can form in the bladder. In most cases bladder stones develop when the urine becomes very concentrated or when one is ...
s.


Size

Stones less than in diameter pass spontaneously in up to 98% of cases, while those measuring in diameter pass spontaneously in less than 53% of cases. Stones that are large enough to fill out the renal calyces are called ''staghorn stones'' and are composed of struvite in a vast majority of cases, which forms only in the presence of urease-forming bacteria. Other forms that can possibly grow to become staghorn stones are those composed of cystine, calcium oxalate monohydrate, and uric acid.


Prevention

Preventative measures depend on the type of stones. In those with calcium stones, drinking plenty of fluids,
thiazide Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...
diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...
s and citrate are effective as is allopurinol in those with high uric acid levels in urine.


Dietary measures

Specific therapy should be tailored to the type of stones involved. Diet can have an effect 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. Dietary recommendations to minimize the formation of kidney stones include * increasing total fluid intake to achieve more than two liters per day of urine output; * limiting cola, including sugar-sweetened soft drinks; to less than one liter per week. * limiting animal protein intake to no more than two meals daily (an association between animal
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
and recurrence of kidney stones has been shown in men); * increasing citrate, or alkali intake, including from lemon and lime juice. However, citric acid does not alkalinize urine like alkali citrate, which is citrate bonded with sodium, potassium and magnesium. This is because when citrate is metabolized (mostly by liver and some by kidney), the protons in citric acid will neutralize the bicarbonate generated, so that no net effect on blood or urine pH will occur. * Reducing sodium intake is associated with a reduction in urine calcium excretion. Maintenance of dilute urine by means of vigorous fluid therapy is beneficial in all forms of kidney stones, 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 per day. A high fluid intake may reduce the likelihood of kidney stone recurrence or may increase the time between stone development without unwanted effects. Calcium binds with available oxalate in the gastrointestinal tract, thereby preventing its absorption into the bloodstream. Reducing oxalate absorption decreases kidney stone risk in susceptible people. Because of this, some doctors recommend increasing dairy intake so that its calcium content will serve as an oxalate binder. Taking calcium citrate tablets during or after meals containing high oxalate foods may be useful if dietary calcium cannot be increased by other means as in those with lactose intolerance. The preferred calcium supplement for people at risk of stone formation is calcium citrate, as opposed to calcium carbonate, because it helps to increase urinary citrate excretion. Aside from vigorous oral hydration and eating more dietary calcium, other prevention strategies include avoidance of higher doses of supplemental (since ascorbate is metabolized to oxalate) and restriction of oxalate-rich foods such as
leaf vegetables Leaf vegetables, also called leafy greens, pot herbs, vegetable greens, or simply greens, are plant leaves eaten as a vegetable, sometimes accompanied by tender petioles and shoots. Leaf vegetables eaten raw in a salad can be called salad ...
, rhubarb,
soy products The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses. Traditional unfermented food uses of soybeans include soy milk, from which tofu a ...
and
chocolate Chocolate is a food made from roasted and ground cacao seed kernels that is available as a liquid, solid, or paste, either on its own or as a flavoring agent in other foods. Cacao has been consumed in some form since at least the Olmec civ ...
. However, no randomized, controlled trial of oxalate restriction has been performed to test the hypothesis that oxalate restriction reduces stone formation. Some evidence indicates
magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...
intake decreases the risk of symptomatic kidney stones.


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 A nephrostomy is an artificial opening created between the kidney and the skin which allows for the urinary diversion directly from the upper part of the urinary system (renal pelvis). An urostomy is a related procedure performed more distally a ...
or retrograde ureteral catheters.
Acetazolamide Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), urine alkal ...
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
alkali citrate Alkali citrate (also known as alkaline citrate) is an inhibitor of kidney stones. It is used to increase urine citrate levels - this prevents calcium oxalate stones by binding to calcium and inhibiting its binding to oxalate. It is also used to in ...
, sodium bicarbonate,
potassium citrate Potassium citrate (also known as tripotassium citrate) is a potassium salt of citric acid with the molecular formula K3C6H5O7. It is a white, hygroscopic crystalline powder. It is odorless with a saline taste. It contains 38.28% potassium by mass ...
,
magnesium citrate Magnesium citrate is a magnesium preparation in salt form with citric acid in a 1:1 ratio (1 magnesium atom per citrate molecule). The name "magnesium citrate" is ambiguous and sometimes may refer to other salts such as trimagnesium citrate wh ...
, 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 Dissolution may refer to: Arts and entertainment Books * ''Dissolution'' (''Forgotten Realms'' novel), a 2002 fantasy novel by Richard Lee Byers * ''Dissolution'' (Sansom novel), a 2003 historical novel by C. J. Sansom Music * Dissolution, in mu ...
of uric acid stones. Increasing the urine pH to a value higher than 7.0 may increase the risk of calcium phosphate stone formation, though this concept is controversial since citrate does inhibit calcium phosphate crystallization. Testing the urine periodically with
nitrazine Nitrazine or phenaphthazine is a pH indicator dye often used in medicine. More sensitive than litmus, nitrazine indicates pH in the range of 4.5 to 7.5. Nitrazine is usually used as the disodium salt. Use *This test is done to ascertain the natu ...
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 of stone radius per month.


Slaked lime

It decreases urinary calcium when combined with food rich in oxalic acid such as green leafy vegetables.


Diuretics

One of the recognized medical therapies for prevention of stones is the
thiazide Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...
and
thiazide-like diuretic A thiazide-like diuretic is a sulfonamide diuretic that has similar physiological properties to a thiazide diuretic, but does not have the chemical properties of a thiazide, lacking the benzothiadiazine molecular structure. Examples include metola ...
s, such as chlorthalidone or
indapamide Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril (an ACE inhibitor antihypertensive) are available. The thiazide-like diuretics ...
. 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 Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...
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 liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
. The drug is also used in people with
gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...
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.


Treatment

Stone size influences the rate of spontaneous stone passage. For example, up to 98% of small stones (less than in diameter) may pass spontaneously through urination within four weeks of the onset of symptoms, but for larger stones ( 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, as well as careful monitoring.


Pain management

Management of pain often requires intravenous administration of Nonsteroidal anti-inflammatory drug, NSAIDs or opioids. NSAIDs appear somewhat better than opioids or paracetamol in those with normal kidney function. Medications by mouth are often effective for less severe discomfort. The use of antispasmodics does not have further benefit.


Medical expulsive therapy

The use of medications to speed the spontaneous passage of stones in the ureter is referred to as medical expulsive therapy. Several agents, including Alpha blocker, alpha adrenergic blockers (such as
tamsulosin Tamsulosin, sold under the brand name Flomax among others, is a medication used to treat symptomatic benign prostatic hyperplasia (BPH) and chronic prostatitis and to help with the passage of kidney stones. The evidence for benefit with a ki ...
) and calcium channel blockers (such as nifedipine), may be effective. Alpha-blockers likely result in more people passing their stones, and they may pass their stones in a shorter time. People taking alpha-blockers may also use less pain medication and may not need to visit the hospital. Alpha-blockers appear to be more effective for larger stones (over 5 mm in size) than smaller stones. However, use of alpha-blockers may be associated with a slight increase in serious, unwanted effects from this medication. A combination of tamsulosin and a corticosteroid may be better than tamsulosin alone. These treatments also appear to be useful in addition to lithotripsy.


Lithotripsy

Extracorporeal shock wave lithotripsy (ESWL) is a noninvasive technique for the removal of kidney stones. Most ESWL is carried out when the stone is present near the renal pelvis. ESWL involves the use of a lithotriptor machine to deliver externally applied, focused, high-intensity pulses of ultrasound, ultrasonic energy to cause fragmentation of a stone over a period of around 30–60 minutes. Following its introduction in the United States in February 1984, ESWL was rapidly and widely accepted as a treatment alternative for renal and ureteral stones. It is currently used in the treatment of uncomplicated stones located in the kidney and upper ureter, provided the aggregate stone burden (stone size and number) is less than and the anatomy of the involved kidney is normal. For a stone greater than , ESWL may not help break the stone in one treatment; instead, two or three treatments may be needed. Some 80-85% of simple renal calculi can be effectively treated with ESWL. A number of factors can influence its efficacy, including chemical composition of the stone, presence of anomalous renal anatomy and the specific location of the stone within the kidney, presence of hydronephrosis, body mass index, and distance of the stone from the surface of the skin. Common adverse effects of ESWL include acute Trauma (medicine), trauma, such as bruise, bruising at the site of shock administration, and damage to blood vessels of the kidney. In fact, the vast majority of people who are treated with a typical dose of shock waves using currently accepted treatment settings are likely to experience some degree of acute kidney injury. ESWL-induced acute kidney injury is dose-dependent (increases with the total number of shock waves administered and with the power setting of the lithotriptor) and can be severe, including internal bleeding and subcapsular hematomas. On rare occasions, such cases may require blood transfusion and even lead to acute kidney failure. Hematoma rates may be related to the type of lithotriptor used; hematoma rates of less than 1% and up to 13% have been reported for different lithotriptor machines. Recent studies show reduced acute tissue injury when the treatment protocol includes a brief pause following the initiation of treatment, and both improved stone breakage and a reduction in injury when ESWL is carried out at slow shock wave rate. In addition to the aforementioned potential for acute kidney injury, animal studies suggest these acute injuries may progress to scar formation, resulting in loss of functional renal volume. Recent Prospective cohort study, prospective studies also indicate elderly people are at increased risk of developing new-onset hypertension following ESWL. In addition, a Retrospective cohort study, retrospective case-control study published by researchers from the Mayo Clinic in 2006 has found an increased risk of developing diabetes mellitus and hypertension in people who had undergone ESWL, compared with age and gender-matched people who had undergone nonsurgical treatment. Whether or not acute trauma progresses to long-term effects probably depends on multiple factors that include the shock wave dose (i.e., the number of shock waves delivered, rate of delivery, power setting, acoustic characteristics of the particular lithotriptor, and frequency of retreatment), as well as certain intrinsic predisposing pathophysiologic risk factors. To address these concerns, the American Urological Association established the Shock Wave Lithotripsy Task Force to provide an expert opinion on the safety and Risk-benefit analysis, risk-benefit ratio of ESWL. The task force published a white paper outlining their conclusions in 2009. They concluded the risk-benefit ratio remains favorable for many people. The advantages of ESWL include its noninvasive nature, the fact that it is technically easy to treat most upper urinary tract calculi, and that, at least acutely, it is a well-tolerated, low-morbidity treatment for the vast majority of people. However, they recommended slowing the shock wave firing rate from 120 pulses per minute to 60 pulses per minute to reduce the risk of renal injury and increase the degree of stone fragmentation. Alpha blocker, Alpha-blockers are sometimes prescribed after shock wave lithotripsy to help the pieces of the stone leave the person's body. By relaxing muscles and helping to keep blood vessels open, alpha blockers may relax the ureter muscles to allow the kidney stone fragments to pass. When compared to usual care or placebo treatment, alpha blockers may lead to faster clearing of stones, a reduced need for extra treatment and fewer unwanted effects. They may also clear kidney stones in more adults than the standard shock wave lithotripsy procedure. The unwanted effects associated with alpha blockers are hospital emergency visits and return to hospital for stone-related issues, but these effects were more common in adults who did not receive alpha-blockers as a part of their treatment.


Surgery

Most stones under pass spontaneously. Prompt surgery may, nonetheless, be required in persons with only one working kidney, bilateral obstructing stones, 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 Ureteroscopy is an examination of the upper urinary tract, usually performed with a ureteroscope that is passed through the urethra and the bladder, and then directly into the ureter. The procedure is useful in the diagnosis and treatment of diso ...
, and
percutaneous nephrolithotomy Percutaneous nephrolithotomy (PCNL) is a minimally-invasive procedure to remove stones from the kidney by a small puncture wound (up to about 1 cm) through the skin. It is most suitable to remove stones of more than 2 cm in size and wh ...
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. Percutaneous nephrolithotomy or, rarely, lithotomy, 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.


Ureteroscopic surgery

Ureteroscopy has become increasingly popular as flexible and rigid optical fiber, fiberoptic ureteroscopes have become smaller. One ureteroscopic technique involves the placement of a Ureteric stent, 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 Acute kidney injury#Postrenal, postrenal acute kidney failure due to the increased hydrostatic pressure, edema, swelling and infection (pyelonephritis and pyonephrosis) caused by an obstructing stone. Ureteral stents vary in length from 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 anesthetic, topical anesthesia after resolution of urolithiasis. Research is currently uncertain if placing a temporary stent during ureteroscopy leads to different outcomes than not placing a stent in terms of number of hospital visits for post operative problems, short or long term pain, need for narcotic pain medication, risk of UTI, need for a repeat procedure or narrowing of the ureter from scarring. More definitive ureteroscopic techniques for stone extraction (rather than simply bypassing the obstruction) include basket extraction and ultrasound ureterolithotripsy. Laser lithotripsy is another technique, which involves the use of a holmium:yttrium aluminium garnet (Ho:YAG) laser to fragment stones in the bladder, ureters, and kidneys. Ureteroscopic techniques are generally more effective than ESWL for treating stones located in the lower ureter, with success rates of 93–100% using Ho:YAG laser lithotripsy. Although ESWL has been traditionally preferred by many practitioners for treating stones located in the upper ureter, more recent experience suggests ureteroscopic techniques offer distinct advantages in the treatment of upper ureteral stones. Specifically, the overall success rate is higher, fewer repeat interventions and postoperative visits are needed, and treatment costs are lower after ureteroscopic treatment when compared with ESWL. These advantages are especially apparent with stones greater than in diameter. However, because ureteroscopy of the upper ureter is much more challenging than ESWL, many urologists still prefer to use ESWL as a first-line treatment for stones of less than 10 mm, and ureteroscopy for those greater than 10 mm in diameter. Ureteroscopy is the preferred treatment in pregnant and morbidly obese people, as well as those with Bleeding diathesis, bleeding disorders.


Epidemiology

Kidney stones affect all geographical, cultural, and racial groups. The Cumulative incidence, lifetime risk is about 10-15% in the developed world, but can be as high as 20-25% 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. The number of deaths due to kidney stones is estimated at 19,000 per year being fairly consistent between 1990 and 2010. In North America and Europe, the annual incidence (epidemiology), number of new cases per year of kidney stones is roughly 0.5%. In the United States, the frequency in the population of urolithiasis has increased from 3.2% to 5.2% from the mid-1970s to the mid-1990s. In the United States, about 9% of the population has had a kidney stone. The total cost for treating urolithiasis was US$2 billion in 2003. About 65–80% of those with kidney stones are men; most stones in women are due to either metabolic defects (such as
cystinuria Cystinuria is an inherited autosomal recessive disease characterized by high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidneys, ureters, and bladder. It is a type of aminoaciduri ...
) or infections in the case of struvite stones. Urinary tract calculi disorders are more common in men than in women. 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. A 2010 review concluded that rates of disease are increasing.


History

The existence of kidney stones was first recorded thousands of years ago, with various explanations given; Joseph Glanville's ''Saducismus Triumphatus,'' for example, gives a detailed description of Abraham Mechelburg's voiding of small stones through his penis' virga, attributing the issue to witchcraft. In 1901, a stone discovered in the pelvis of an ancient Egyptian mummy was dated to 4,800 BC. Medical texts from ancient Mesopotamia, History of India, India, History of China, China, Achaemenid Empire, Persia, Ancient Greece, Greece, and Ancient Rome, 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 Lithotomy, lithotomies, or the surgical removal of stones. 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. Examples of people who had kidney stone disease include Napoleon I, Epicurus, Napoleon III, Peter the Great, Louis XIV of France, Louis XIV, George IV of the United Kingdom, 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 Flugzeugwerke, Dornier MedTech introduced extracorporeal shock wave lithotripsy for breaking up stones via acoustical pulses, and this technique has since come into widespread use.


Etymology

The term ''renal calculus'' is from the Latin ''rēnēs'', meaning "kidneys", and ''Calculus (medicine), calculus'', meaning "pebble". Lithiasis (stone formation) in the kidneys is called nephrolithiasis (), from ''wikt:nephro-, nephro-'', meaning kidney, + ''wikt:-lith, -lith'', meaning stone, and ''wikt:-iasis#Suffix, -iasis'', meaning disorder. A distinction between nephrolithiasis and urolithiasis can be made because not all urinary stones (uroliths) form in the kidney; they can also form in the bladder. But the distinction is often clinically irrelevant (with similar disease process and treatment either way) and the words are thus often used loosely as synonyms.


Children

Although kidney stones do not often occur in children, the incidence is increasing. These stones are in the kidney in two thirds of reported cases, and in the
ureter The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...
in the remaining cases. Older children are at greater risk independent of whether or not they are male or female. As with adults, most pediatric kidney stones are predominantly composed of calcium oxalate; struvite and
calcium phosphate The term calcium phosphate refers to a family of materials and minerals containing calcium ions (Ca2+) together with inorganic phosphate anions. Some so-called calcium phosphates contain oxide and hydroxide as well. Calcium phosphates are whi ...
stones are less common. Calcium oxalate stones in children are associated with high amounts of calcium, oxalate, and magnesium in acidic urine. Treatment of kidney stones in children are similar to treatments for adults including: shock wave lithotripsy, medication, and treatment using scope through the bladder, kidney or skin. Of these treatments, research is uncertain if shock waves are more effective than medication or a scope through the bladder, but it is likely less successful than a scope through skin into the kidney. When going in with a scope through the kidney, a regular and a mini-sized scope likely have similar success rates of stone removal. Alpha-blockers, a type of medication, may increase the successful removal of kidney stones when compared with a placebo and without ibuprofen.


Research

Metabolic syndrome and its associated diseases of obesity and diabetes as general risk factors for kidney stone disease are under research to determine if urinary excretion of calcium, oxalate and urate are higher than in people with normal weight or underweight, and if diet and physical activity have roles. Dietary, fluid intake, and lifestyle factors remain major topics for research on prevention of kidney stones, as of 2017.


Gut microbiota

The gut microbiota has been explored as a contributing factor for stone disease, indicating that some bacteria may be different in people forming kidney stones. One bacterium, ''Oxalobacter formigenes'', is potentially beneficial for mitigating calcium oxalate stones because of its ability to metabolize oxalate as its sole carbon source, but 2018 research suggests that it is instead part of a network of oxalate degrading bacteria. Additionally, one study found that oral antibiotic use, which alters the gut microbiota, can increase the odds of a person developing a kidney stone.


In animals

Among ruminants, uroliths more commonly cause problems in males than in females; the sigmoid flexure of the ruminant male urinary tract is more likely to obstruct passage. Early-castrated males are at greater risk, because of lesser urethral diameter. Low Ca:P intake ratio is conducive to phosphatic (e.g. struvite) urolith formation. Incidence among wether lambs can be minimized by maintaining a dietary Ca:P intake ratio of 2:1. Alkaline (higher) pH favors formation of #Composition, carbonate and phosphate calculi. For domestic ruminants, dietary cation: anion balance is sometimes adjusted to assure a slightly acidic urine pH, for prevention of calculus formation. Differing generalizations regarding effects of pH on formation of silicate uroliths may be found. In this connection, it may be noted that under some circumstances, calcium carbonate accompanies silica in siliceous uroliths. Pelleted feeds may be conducive to formation of phosphate uroliths, because of increased urinary phosphorus excretion. This is attributable to lower saliva production where pelleted rations containing finely ground constituents are fed. With less blood phosphate partitioned into saliva, more tends to be excreted in urine. (Most saliva phosphate is fecally excreted.) Oxalate uroliths can occur in ruminants, although such problems from oxalate ingestion may be relatively uncommon. Ruminant urolithiasis associated with oxalate ingestion has been reported. However, no renal tubular damage or visible deposition of calcium oxalate crystals in kidneys was found in yearling wether sheep fed diets containing soluble oxalate at 6.5 percent of dietary dry matter for about 100 days. Conditions limiting water intake can result in stone formation. Various surgical interventions, e.g. amputation of the urethral process at its base near the glans penis in male ruminants, perineal urethrostomy, or tube cystostomy may be considered for relief of obstructive urolithiasis.


See also

* Nephrocalcinosis * Kidney disease


References


Notes

* * * *


External links

*
Information from the European Urological Association

Kidney Stone Guide Book
– University of Chicago Kidney Stone Program {{Use dmy dates, date=April 2018 Kidney diseases Urological conditions Acute pain Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate