Urolithiasis denotes presence of stones of various composition in the urinary tract, with calcium oxalate being the most common. Prevalence rates in the general population suggest that this condition is rather common, and causes may be numerous. Abdominal pain, nausea, vomiting and hematuria are the most common symptoms. The diagnosis is made by clinical findings together with laboratory and imaging studies. Conservative therapy, lithotripsy and dietary changes are the main principles of treatment and prevention.
Urolithiasis is often asymptomatic, as smaller calculi ( < 5 mm) pass through the ureters unnoticed and do not produce any symptoms. Larger stones, however, may obstruct the ureters during their passage through the collecting system and cause obstruction. As a result, symptoms such as nausea, vomiting and gross hematuria may appear. Abdominal pain that is described as intermittent and very intensive (renal colic) is one of the most common symptoms reported in adults. The pain can radiate to the groin or to the genitalia, which indirectly indicates the site of obstruction . In children, however, the pain is nonspecific and gross hematuria is more often encountered, up to 90% according to certain reports . In the setting of a UTI, fever may be present, while dysuria and increased frequency of urination is reported in 10% of patients . In infants, restlessness may be the only symptoms and ultrasonographic examination is advocated in these patients .
The initial diagnosis of urolithiasis can be made based on findings during clinical examination and information obtained during patient history that is focused on signs and symptoms, but also dietary habits (intake of water and calcium). Hematuria and renal colic can strongly suggest urinary tract disease and the diagnosis can be confirmed by laboratory and imaging studies. In patients with suspected urolithiasis, laboratory investigation should comprise urinalysis (pH, specific gravity, bacteria and nitrites and crystals), serum electrolytes (including calcium potassium, magnesium, sodium), uric acid, blood urea nitrogen, creatinine and vitamin D levels . In the setting of hypercalcemia, PTH levels should be obtained. If a UTI is suspected, urine cultures can be performed. To confirm the presence of stones in the ureters, helical CT is the imaging technique of choice, while ultrasonography may be an alternative method. If urolithiasis is confirmed, but initial laboratory values are within physiological range, an extensive urinalysis that includes evaluation of oxalate, citrate, calcium and total urine volume should be performed .
Depending on the severity of symptoms and the degree of obstruction, various therapeutic modalities exist. Smaller calculi that cause milder symptoms and show no signs of obstruction are managed by a conservative approach, known as medical expulsion therapy (MET). The goal is to facilitate excretion of calculi without the use of invasive procedures. Fluid administration and analgesics (NSAIDs, but in pregnancy, opioids are used) are the mainstay of therapy , together with α-receptor blockers such as tamulsosin or calcium-channel antagonists (nifedipine) was shown to be quite useful . If calculi have not been expelled within 6 weeks, however, mechanical removal is required . Various techniques exist, such as extracorporeal shock wave lithotripsy, which uses ultrasounds to break down calculi, but ureteroscopy is shown to be the gold standard . In severe cases, endoscopy and open surgery may be indicated.
The prognosis of patients with urolithiasis is quite good, as therapy provides very good outcomes regardless of the severity of the disease. Although there is an increased risk for recurrence (15% of patients develop another calculus 1 year after, 40% after 5 years and 80% after 10 years) , appropriate preventive strategies can substantially reduce the risk of recurrence. The diagnosis must be made promptly, however, as larger stones may significantly impair normal renal blood flow and cause significant renal damage if left untreated.
The causes of urolithiasis are diverse and vary depending on the composition of stones   :
- Calcium stones (calcium oxalate and phosphate) comprise almost 85% of all calculi and they develop from conditions such as hereditary hypercalciuria and hypocitruria, while other less common causes include renal tubular acidosis, hyperparathyroidism, hyperoxaluria and sarcoidosis. In children, hypercalciuria is present in approximately 50-70% of calcium oxalate stones and many diseases have been implicated in the pathogenesis, in addition to those mentioned above, including hypervitaminosis D, malignancy and adrenal insufficiency. In a substantial number of patients, however, hypercalciuria without an identifiable cause (idiopathic hypercalciuria) is the most common cause of increased calcium excretion .
- Magnesium ammonium phosphate (struvite) stones are seen in a small percentage of patients (< 5%) and develop in the setting of an infection by urease-positive bacteria, such as Proteus and Klebsiella sp.
- Uric acid calculi develop under circumstances of reduced acidity of urine or hyperuricosuria, which arises from conditions such as purine metabolism disorders, polycythemia and hematologic malignancy.
- Cystinuria is an autosomal recessive disease in which significantly higher amounts of cystine is excreted through urine and because of its poor solubility, aggregation of this compound result in cystine stone formation.
Urolithiasis is shown to be a rather common finding in the general population, as prevalence rates range between 4-20% across different studies . Moreover, it is estimated that about 1 in 1000 adults is hospitalized because of urolithiasis every year in the United States . This condition more commonly arises in men and approximately 13% of males and 7% of women will suffer from this condition by the age of 70 . However, struvite stones are much more likely to develop in females , presumably because they arise in the setting of a urinary tract infection (UTI), which is much more frequent among females. In terms of risk factors, obesity is shown to be one of the most important, as various metabolic and renal changes create favorable conditions for stone formation . In the pediatric population, genitourinary anomalies such as hydronephrosis and duplex ureter are found in approximately 30% of children with urolithiasis . Although high intake of calcium and uric acid should consequently lead to higher calcium excretion and hypercalciuria, it actually reduces the risk of ion supersaturation . Low urine volume, on the other hand, mainly as a result of chronic dehydration, is established to be a significant risk factor . In pregnancy, urolithiasis is established to be the most common cause of nonobstetric hospital admission, because various factors promote stone formation during this period, such as mechanical compression of ureters, urine pH changes and accelerated excretion of calcium uric acid and sodium .
The pathogenesis model somewhat depends on the type of stone that is formed. In general, urine volume, pH, the concentration of stone forming-ions, such as calcium, magnesium and cystine and quantitative presence of inhibitors and inducers of ion crystallization are considered as the most important mediators in urolithiasis . In calcium oxalate and phosphate stones, increased calcium concentration in urine facilitates the process of crystallization. Additionally, the concentrations of citrate, one of the main inhibitors of Ca stone formation, is reduced, as it normally binds to Ca and neutralizes its capacity for crystallization . In uric acid and cystine stones, the initial pathogenic mechanism is acidification of pH, as these crystals are more likely to precipitate and fuse in an acidic environment (pH < 7.5 and 6.0, respectively), whereas calcium phosphate stones are more likely to develop in alkali urine. . Oxalate is another stone-forming ion that is excreted through urine in increased amounts (either as a result of higher dietary intake or hereditary disorders that impair its metabolism) . Its interaction with calcium leads to crystallization and development of calcium oxalate stones, the most common type encountered in medical practice. Low urine volume, however, is one of the most important pathological events that produces favorable conditions for all stones, as saturation of stone-forming ions such as oxalate and calcium occurs . Bacterial pathogens that contain urease, an enzyme that breaks down urea, are thought to be the most important mediators of struvite stone evolution, but recent studies indicate that some other factors may be implicated in the pathogenesis .
Fortunately, urolithiasis can be significantly reduced in the general population through various preventive strategies. Correction of fluid intake and urine dilution with high intake of fluids is considered to be one of the most effective preventive measure . Body mass index should be corrected through appropriate dietary changes is also vital, as obesity is shown to be an important risk factors . In patients with hereditary hypercalciuria, prophylactic use of thiazide diuretics that lowers Ca excretion may permanently reduce the incidence of urolithiasis in this population, whereas uric acid stones can be prevented either by reduction of uric acid-rich foods such as meat, fish and poultry or administration of allopurinol .
Urolithiasis is a term that implies the presence of stones in the ureteral system. The vast majority of stones are composed of calcium oxalate and they develop in conditions such as hereditary hypercalciuria, hyperparathyroidism and renal tubular acidosis . Calcium phosphate, magnesium phosphate (struvite), cystine and uric acid stones are other types that are encountered in various percentages . Urolithiasis is a rather common finding in medical practice, as prevalence rates range between 3-20% according to different studies  . Moreover, studies from the United States show that 1 in 1000 patients are admitted to the hospital because of urolithiasis . The pathogenesis of urinary calculi starts in the renal parenchyma, where either increased amount of calcium, changes in urinary pH (both marked reduction and alkalinization), or presence of an infection (struvite stones are created in the presence of urease-positive bacteria) facilitates stone formation . Lower urine volume, however, is the most important risk factor, as subsequent supersaturation of certain ions that normally inhibit the development of stones occurs in such conditions . Citrate is one of these ions and serves as one of the main inhibitors of calcium oxalate formation since it directly binds to calcium ions and reduces the capacity for crystallization of calcium . Smaller calculi are asymptomatic and pass through the ureters unnoticed, but larger calculi (> 5 mm) can lodge in the ureters and cause obstruction that produces symptoms. Abdominal pain (renal colic), nausea, vomiting and hematuria may be seen. To make the diagnosis, laboratory studies that encompass urinalysis, serum electrolyte levels (including calcium and phosphorus), kidney function tests (blood urea nitrogen and creatinine), uric acid, as well as parathyroid hormone (PTH) and vitamin D should be conducted . Helical computed tomography (CT) is the gold standard in the diagnosis of urolithiasis, as it can identify the site and the extent of ureter obstruction with great precision, while ultrasonography is considered as an alternative. Treatment principles somewhat vary depending on the underlying cause, but destruction of stones through various techniques is recommended. Medical expulsive therapy (MET) consisting of fluids, tamulsosin and nifedipine, extracorporeal shock wave lithotripsy and ureterorenoscopy are used, whereas massive stones are managed with either open or laparoscopic surgery . Hydration, supplementation, thiazide diuretics, dietary changes, antimicrobial therapy and surgery are modalities used depending on the underlying etiology .
Urolithiasis is a term that is used to describe the presence of stones in the urinary tract. This condition is relatively common in the Western world, as studies have determined that up to 5-20% of the population is shown to have some form of urolithiasis. In pregnancy, urolithiasis is reported to be the most common cause of nonobstetric hospital admission. Stones may be composed of different substances, but calcium stones are identified in almost 90% of cases. They may form in diseases that promote increased excretion of calcium, such as hereditary hypercalciuria, hyperparathyroidism, vitamin D intoxication and a plethora of conditions that increase levels of calcium in urine. In many diseases that promote calcium stone formation, however, blood levels of calcium may be normal or even reduced. Other stone types include magnesium phosphate, or struvite, which are seen in the setting of a urinary tract infection by organisms that degrade urea (such as Proteus and Klebisella), uric acid stones that are produced in diseases that facilitate uric acid excretion or reduce urine pH, and cystine stones that are formed in cystinuria, a hereditary disorder characterized by hyperexcretion of cystine. Low urine volume provoked by chronic dehydration and obesity are shown to be the most important risk factors for urolithiasis. Low fluid intake leads to saturation of various ions in urine and creates favorable conditions for their fusion and formation of crystals, whereas obesity causes several deleterious effects on the kidneys and impairs normal metabolic function. This conditions is somewhat more commonly seen in males, but struvite stones are much more frequently encountered in women, as urinary tract infections are much more common among females. The clinical course of urolithiasis is usually asymptomatic, as many stones are passed through urine undetected, but larger stones (> 5 mm in diameter) can obstruct urine passage and damage the ureters. Under these circumstances, symptoms such as nausea, vomiting and intense abdominal pain that appears intermittently are most frequently encountered. Hematuria (blood in urine) may be often detected and is more common in children. To make the diagnosis, inspection of urine and evaluation of electrolytes and kidney function is necessary. To confirm the presence of stones in ureters, computed tomography (CT scan) is the recommended imaging techniques. Treatment approaches depend on the severity of symptoms and range from administration of painkillers, fluids and drugs that facilitate stone excretion (tamulsosin and nifedipine), to mechanical removal via various techniques. The use of ultrasound waves to break down stones (known as shock wave lithotripsy) and retrograde insertion of an endoscope with laser-mediated stone destruction (ureteroscopy and laser lithotripsy) are the two most common procedures used in medical practice, and they are indicated when conservative therapy fails. In severe cases, endoscopic or open surgery may be performed as the last line of therapy. Preventive strategies depend on the underlying cause, but increased hydration and adequate dietary changes are the mainstay in reducing the rates of urolithiasis in the general population.
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