Kidney stone disease or urinary stone disease is a crystallopathy that occurs when there is an excess of minerals in the urine and not enough liquid or hydration. This imbalance causes tiny crystals to aggregate and form hard masses, or calculi (stones), in the upper urinary tract. Because renal calculi typically form in the kidney, if small enough they may pass out of the urinary tract through the urine stream. A small calculus may pass without causing any symptoms. However, if a stone grows to more than , it can cause blockage of the ureter, resulting in extremely sharp and severe pain (renal colic) in the lower back that often radiates to the groin. A calculus may also result in blood in the urine, vomiting (owing to severe pain), swelling of the kidney, or painful urination. About half of all people who have had a kidney stone are likely to develop another within ten years.
Renal is Latin for "kidney", while nephro is the Greek equivalent. Lithiasis (Greek) and calculus (Latin; plural calculi) both mean stone. Hence, kidney stones are sometimes known as renal calculi or nephroliths, and the condition may be known as nephrolithiasis.
Most calculi form by a combination of genetics and environmental factors. Risk factors include high urine calcium levels, obesity, certain foods, some medications, calcium supplements, gout, hyperparathyroidism, and not drinking enough fluids. Calculi form in the kidney when minerals in urine are at high concentrations. The diagnosis is usually based on symptoms, urine testing, and medical imaging. Blood tests may also be useful. Calculi are typically classified by their location, being referred to medically as nephrolithiasis (in the kidney), ureterolithiasis (in the ureter), or cystolithiasis (in the bladder). Calculi are also classified by what they are made of, such as calcium oxalate, uric acid, struvite, or cystine.
In those who have had renal calculi, drinking fluids, especially water, is a way to prevent them. Drinking fluids such that more than two liters of urine are produced per day is recommended. If fluid intake alone is not effective, medications such as thiazide diuretics, citrate, or allopurinol may be suggested. Soft drinks containing phosphoric acid (typically colas) should be avoided. When a calculus causes no symptoms, no treatment is needed. For those with symptoms, pain control is usually the first measure, using medications such as nonsteroidal anti-inflammatory drugs or opioids. Larger calculi may be helped to pass with the medication tamsulosin or may require procedures for removal such as extracorporeal shockwave therapy (ESWT), laser lithotripsy (LL), or percutaneous nephrolithotomy (PCNL).
Renal calculi have affected humans throughout history, with descriptions of surgery to remove them dating from as early as 600 BC in ancient India by Sushruta. Between 1% and 15% of people globally are affected by renal calculi at some point in their lives. In 2015, about 22.1 million cases occurred, resulting in about 16,100 deaths. They have become more common in the Western world since the 1970s. Generally, more men are affected than women, mainly between the ages of 40 and 60. The prevalence and incidence of the disease continue to rise worldwide.
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, restlessness, frequent urination, blood in the urine, sweating, nausea, and vomiting. It typically comes in waves lasting 20 to 60 minutes, caused by peristaltic contractions of the ureter as it attempts to expel the stone.
The embryological link between the urinary tract, the genital system, and the gastrointestinal tract is the basis of the radiation of pain to the gonads, as well as the nausea and vomiting that are also common in urolithiasis. Postrenal azotemia and hydronephrosis can be observed following the obstruction of urine flow through one or both ureters.
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 from low fluid intake is a 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, sodium, sugars including honey, refined sugars, fructose and high fructose corn syrup, and excessive consumption of fruit juices may increase the risk of kidney stone formation due to increased uric acid 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, Dent's disease, hyperparathyroidism, primary hyperoxaluria, or medullary sponge kidney. 3–20% of people who form kidney stones have medullary sponge kidney.
Kidney stones are more common in people with Crohn's disease; it is associated with hyperoxaluria and malabsorption of magnesium.
Ureteropelvic junction obstruction (UPJO), a congenital or acquired condition characterized by a narrowing of the junction between the renal pelvis and the ureter, impeding the flow of urine to the bladder, is a contributing factor in the formation of kidney stones.
Twin studies conducted in 2005 estimated the heritability of kidney stone development at . Similarly, up to two-thirds of individuals with hypercalciuric stone formation have a family history of nephrolithiasis.
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 as a dietary supplement have a higher risk of developing kidney stones. In the United States, kidney stone formation was used as an indicator of excess calcium intake by the Reference Daily Intake committee for calcium in adults.
In the early 1990s, a study conducted for the Women's Health Initiative in the US found that postmenopausal women who consumed 1000 mg of supplemental calcium and 400 international units of vitamin D per day for seven years had a 17% higher risk of developing kidney stones than subjects taking a placebo. The Nurses' Health Study also showed an association between supplemental calcium intake and kidney stone formation.
Unlike supplemental calcium, high intakes of dietary calcium do not appear to cause kidney stones and may actually protect against their development. This is perhaps related to the role of calcium in binding ingested oxalate in the gastrointestinal tract. As the amount of calcium intake decreases, the amount of oxalate available for absorption into the bloodstream increases; this oxalate is then excreted in greater amounts into the urine by the kidneys. In the urine, oxalate is a strong promoter of calcium oxalate precipitation—about 15 times stronger than calcium.
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.
There is no evidence that drinking typical concentrations of fluoridated tap water (≤ 1 ppm) increases the risk of kidney stones. Increased consumption of tap water was associated with lower prevalence of kidney stones compared to bottled water, which typically have lower levels of fluoride supplementation.
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 reduces citrate. Urinary excretion of excess sulfurous amino acids (e.g., cysteine and methionine), uric acid, and other acidic metabolites from animal protein acidifies the urine, which promotes the formation of kidney stones. 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 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 Kidney stones are primarily composed of calcium salts, with the most common being calcium oxalate (70-80%), followed by calcium phosphate and uric acid. When urine contains high concentrations of these ions, they can form crystals and eventually stones.
The formation of kidney stones occurs in three main phases: nucleation (initial crystal formation) growth (expansion of single crystals) aggregation (clumping of multiple crystals)
When the urine becomes supersaturated (when the urine solvent contains more solutes than it can hold in solution) with one or more calculogenic (crystal-forming) substances, initial seed crystals 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, a seed crystal can grow and aggregate into an organized mass. Depending on the chemical composition of the crystal, the stone-forming process may proceed more rapidly when the urine pH is unusually high or low.
Supersaturation of the urine with respect to a calculogenic compound is pH-dependent. For example, at a pH of 7.0, the solubility of uric acid in urine is 158 mg/100 mL. Reducing the pH to 5.0 decreases the solubility of uric acid to less than 8 mg/100 mL. The formation of uric-acid stones requires a combination of hyperuricosuria (high urine uric-acid levels) and low urine pH; hyperuricosuria alone is not associated with uric-acid stone formation if the urine pH is alkaline. Supersaturation of the urine is a necessary, but not a sufficient, condition for the development of any urinary calculus. Supersaturation is likely the underlying cause of uric acid and cystine stones, but calcium-based stones (especially calcium oxalate stones) may have a more complex cause.
Randall's plaque