INTRODUCTION — Kidney stone disease (nephrolithiasis) is a common problem in primary care practice. Patients may present with the classic symptoms of renal colic and hematuria. Others may be asymptomatic or have atypical symptoms such as vague abdominal pain, acute abdominal or flank pain, nausea, urinary urgency or frequency, difficulty urinating, penile pain, or testicular pain.
Primary care clinicians need to be alert to the possibility of nephrolithiasis and its consequences to decide upon a diagnostic approach, therapy, and the need for referral to a urologist. These issues will be reviewed here. Other aspects of kidney stones in adults are discussed separately:
●(See "Kidney stones in adults: Epidemiology and risk factors".)
●(See "Kidney stones in adults: Evaluation of the patient with established stone disease".)
●(See "Kidney stones in adults: Surgical management of kidney and ureteral stones".)
●(See "Kidney stones in adults: Prevention of recurrent kidney stones".)
ETIOLOGY — Eighty percent of patients with nephrolithiasis form calcium stones, most of which are composed primarily of calcium oxalate or, less often, calcium phosphate [1,2]. The other main types include uric acid, struvite (magnesium ammonium phosphate), and cystine stones. The same patient may have a stone that contains more than one crystal type (eg, calcium oxalate and uric acid) .
There are different theories regarding calcium stone formation, and the different stone types may have different initiating events. Stone formation occurs when normally soluble material (eg, calcium, oxalate) supersaturates the urine and begins the process of crystal formation (eg, calcium oxalate crystal). For some calcium stones, particularly calcium oxalate, it appears that an important initiating event occurs in the kidney medullary interstitium [4-6]. Calcium phosphate crystals may form in the interstitium and eventually erode through the kidney papillary epithelium, forming the classic Randall's plaque [5,6]. Calcium oxalate or calcium phosphate crystals may then deposit on top of this nidus, remaining attached to the papilla. Calcium phosphate stones might also form initially in dilated ducts of Bellini and then grow out into the urinary space .
The pathogenesis of struvite, cystine, and uric acid stones is discussed separately:
●(See "Kidney stones in adults: Struvite (infection) stones".)
●(See "Kidney stones in adults: Uric acid nephrolithiasis".)
●(See "Cystinuria and cystine stones".)
Asymptomatic stones — Patients may occasionally be diagnosed with asymptomatic nephrolithiasis when an imaging exam of the abdomen is performed for other purposes or when surveillance imaging is performed in those with a prior history of stones. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on 'Patients with asymptomatic stones'.)
The asymptomatic phase is more likely to persist in those who have never had a clinical episode of renal colic. A study of 107 patients with asymptomatic stones, for example, found that almost 70 percent remained symptom free during the 31 months of follow-up; a linear association was noted between the development of a symptomatic event and the number of previous stones [8,9].
Pain — Symptoms may develop when stones initially pass from the renal pelvis into the ureter. Pain is the most common symptom and varies from a mild and barely noticeable ache to discomfort that is so intense that it requires parenteral analgesics. The pain typically waxes and wanes in severity and develops in waves or paroxysms. Paroxysms of severe pain usually last 20 to 60 minutes. Pain is thought to occur primarily from urinary obstruction with distention of the kidney capsule. Consequently, pain due to a kidney stone typically resolves quickly after passage of the stone.
The site of obstruction determines the location of pain. Upper ureteral or kidney pelvic obstruction lead to flank pain or tenderness, whereas lower ureteral obstruction causes pain that may radiate to the ipsilateral testicle or labium. The location of the pain may change as the stone migrates. Many patients familiar with the symptoms are able to predict whether the stone has passed through the ureter. However, stones that are impacted or do not migrate cannot be localized with certainty based on symptoms alone. In addition, a variable location of pain can be misleading and occasionally mimics an acute abdomen or dissecting aneurysm. In some patients with chronic back pain, the diagnosis of acute colic may be difficult without an imaging exam.
Patients occasionally present after having passed gravel or a stone. Patients who form uric acid stones frequently describe passing gravel, but uric acid stones can also produce acute obstruction.
Hematuria — Gross or microscopic hematuria occurs in the majority of patients presenting with symptomatic nephrolithiasis (but is also often present in asymptomatic patients). Other than passage of a stone or gravel, this is one of the most discriminating predictors of a kidney stone in patients presenting with unilateral flank pain. One study, for example, found that two-thirds of patients with a ureteral stone had hematuria . (See 'Diagnostic imaging' below.)
On the other hand, the absence of hematuria in the setting of acute flank pain does not exclude the presence of nephrolithiasis [3,11]. Hematuria is not detected in approximately 10 to 30 percent of patients with documented nephrolithiasis [10,12,13]. One factor that may undermine the sensitivity of hematuria is the interval from the onset of acute pain to the time of urine examination. In a retrospective study of over 450 patients with computed tomography (CT)-documented acute ureterolithiasis, hematuria was present in 95 percent on day 1 and 65 to 68 percent on days 3 and 4 .
Other symptoms — Other symptoms that are commonly seen include nausea, vomiting, dysuria, and urinary urgency. The last two complaints typically occur when the stone is located in the distal ureter.
Complications — Nephrolithiasis may lead to persistent kidney obstruction, which could cause permanent kidney damage if left untreated. If urine is infected proximal to the obstructing stone, this is a urologic emergency that requires rapid decompression either by a ureteral stent or a nephrostomy tube. This is a situation in which a patient could become septic very quickly if left untreated. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Emergency surgery'.)
Staghorn calculi themselves do not typically produce symptoms unless the stone results in urinary tract obstruction or an infection is the cause of the staghorn calculus. However, they can lead to kidney failure over years if they are present bilaterally. One study found that deterioration in kidney function occurred in 28 percent of patients with staghorn calculi over an eight-year period . (See "Kidney stones in adults: Struvite (infection) stones".)
EVALUATION OF SUSPECTED NEPHROLITHIASIS — The diagnosis of nephrolithiasis should be suspected in any patient presenting with renal colic or flank pain, with or without hematuria, particularly if the patient has a prior history of stone disease. Such patients should undergo laboratory testing and imaging of the kidneys, ureters, and bladder to confirm the presence of a stone and assess for signs of urinary obstruction (algorithm 1 and algorithm 2).
Laboratory testing — All patients presenting with suspected nephrolithiasis should undergo basic laboratory testing. We obtain a basic metabolic panel to assess kidney function and a urinalysis to evaluate for hematuria and signs of urinary tract infection. Although pyuria may be present even in the absence of bacteriuria, the combination of pyuria and positive testing for nitrites on the urinalysis should raise the suspicion for a concurrent urinary tract infection. (See "Urinalysis in the diagnosis of kidney disease".)
Diagnostic imaging — Patients with suspected nephrolithiasis should undergo an imaging study to determine if a kidney stone is present and to assess for signs of urinary obstruction (eg, hydronephrosis) (algorithm 2). If a stone is detected, stone size and location are used to predict the likelihood of spontaneous passage and guide management (algorithm 1) . In addition, the density and appearance of a stone on computed tomography (CT) can sometimes be used to predict its mineral composition, which is important in informing treatment. Recent passage of a ureteral stone can also be suggested by imaging findings of pyeloureteral dilatation, sometimes accompanied by perinephric stranding.
Selection of modality — CT of the abdomen and pelvis without contrast performed using low-radiation-dose protocols is the preferred examination for most adults with suspected nephrolithiasis. If CT technology is not available, ultrasound of the kidneys and bladder, sometimes in combination with abdominopelvic radiography, is the second-line option for initial imaging. This choice is determined by considerations of diagnostic accuracy, cumulative radiation dose over time, and the need for treatment planning information should the examination prove positive. Other available, but less frequently used, modalities for evaluating patients with suspected nephrolithiasis include intravenous pyelography (IVP) and magnetic resonance imaging (MRI) of the abdomen and pelvis (table 1); such modalities should only be used if CT and ultrasound are not available.
Patients who could potentially be pregnant should undergo screening for pregnancy (ie, a urine or serum pregnancy test) before CT or abdominal radiography. (See "Clinical manifestations and diagnosis of early pregnancy", section on 'Types of pregnancy tests'.)
Choice of imaging should include consideration of the following (algorithm 2):
●CT of the abdomen and pelvis without contrast performed using low-radiation-dose scanning technology is the preferred examination for most adults as it reliably detects hydronephrosis and demonstrates the highest diagnostic accuracy for nephrolithiasis. This examination is available at most sites. If positive, CT also accurately describes stone size and location for treatment planning. It also provides accurate information on the size and number of other stones in the kidneys. Reasons not to perform a low-dose CT, even if available, are as follows:
•If the patient is pregnant, an ultrasound is the preferred modality. (See "Kidney stones in adults: Kidney stones during pregnancy", section on 'Diagnosis in pregnancy'.)
•If the patient has a body mass index (BMI) >30 kg/m2 or weighs more than 130 kg (male) or 115 kg (female), then a standard-dose CT is performed.
●If low-radiation-dose CT is not available, ultrasound of the kidneys and bladder, sometimes in combination with abdominopelvic radiography, is the second-line alternative. In patients who have undergone or are likely to undergo multiple CT exams for nephrolithiasis, and in pregnant patients, ultrasound is preferred as it minimizes the cumulative radiation dose over time. Ultrasound reliably detects hydronephrosis, and radiography can be used to measure stone size and location. However, compared with CT, both ultrasound and radiography are less sensitive for detecting stones. Thus, many patients who initially undergo ultrasound will require a follow-up CT to either identify a stone or to guide management. Noncontrast CT is preferred over ultrasound in patients with large body habitus or end-stage kidney disease (ESKD).
Point-of-care kidney ultrasound at the bedside is performed in many emergency departments within the United States. While it is followed by CT for the majority of cases requiring intervention, this does not result in significant care delay. However, an observational study examining imaging trends for suspected urinary stone disease in United States emergency departments found that use of ultrasound has remained relatively low (approximately 2 percent) compared with use of CT (59 percent) .
Noncontrast CT — Computed tomography (CT) of the abdomen and pelvis without contrast reliably detects hydronephrosis and demonstrates the best diagnostic performance for nephrolithiasis. For detecting ureteral calculi, sensitivity and specificity of CT using conventional radiation doses is >0.94 and >0.97, respectively (image 1A-B) [17-20]. CT performed using low-radiation-dose protocols (image 2) should be used as the technique demonstrates high diagnostic accuracy with pooled sensitivity and specificity of 0.97 (95% CI 0.95-0.98) and 0.95 (95% CI 0.92-0.97), respectively [17,18,21-24]. Low-dose CT may be less reliable for detecting small stones (<2 mm) and ureteral stones in patients with obesity (BMI >30 mg/k2). However, sensitivity for detection of stones >3 mm is not altered with dose reduction in patients without obesity [25,26]. For assessing stone size, low- and standard-dose CT exams yield equivalent measurements .
The effective radiation dose of a standard, noncontrast abdominopelvic CT is usually 10 to 12 mSv. By convention, the upper limit of effective radiation dose for low-dose, noncontrast CT is 4 mSv, although most examinations fall in the 2 to 3 mSv range, a dose that is slightly higher than that conferred by radiography (see 'Abdominal radiography' below). Imaging is performed on a multidetector CT scanner with 1 to 5 mm slice thickness. Techniques for lowering radiation dose while maintaining image quality include automated tube current modulation and iterative reconstruction .
Intravenous contrast is usually not administered, as it decreases sensitivity for small stones. However, for detecting stones >3 mm, contrast-enhanced CT demonstrates 0.95 sensitivity and is comparable with noncontrast CT. Thus, if a contrast-enhanced CT exam has already been performed, it is useful in detecting clinically significant stones.
Occasionally, a contrast-enhanced abdominopelvic CT will follow a low-dose, noncontrast CT to differentiate a high-density focus as a ureteral stone rather than a periureteral phlebolith . Contrast excretion maps the ureteral lumen unambiguously and enables localization of a high-density focus to within, rather than alongside, the ureter.
Noncontrast CT can usually detect secondary signs of urinary tract obstruction [30,31]. The likelihood of detecting these findings varies with the duration of pain. In a report of 227 patients with acute nephrolithiasis, ureteral dilatation was seen in 84 and 97 percent at two and eight hours, respectively, and moderate to severe perinephric stranding in 5 and 51 percent at two and eight hours, respectively .
Determination of stone composition — The appearance, density, and location of a stone on CT may suggest its composition. In general, uric acid, cystine, and struvite stones can usually be distinguished from calcium oxalate calculi. Density is measured in Hounsfield units by drawing regions of interest on CT images.
●Although magnesium ammonium phosphate and cystine stones are often radiopaque on CT, they are not as dense as stones composed of calcium oxalate or calcium phosphate. Uric acid stones tend to demonstrate lower density than calcium stones.
●Large calculi in the renal pelvis favor struvite stones (image 1B). Struvite stones usually have a component of carbonate apatite mixed in, which is responsible for their usual radiodensity.
●Nephrocalcinosis is more commonly associated with calcium phosphate stones.
●Medullary sponge kidney with bilateral calcifications at the corticomedullary junction is associated with calcium oxalate or calcium phosphate stones (image 3). (See "Medullary sponge kidney", section on 'Imaging findings'.)
●Stones that are radiolucent, which can go undetected even on CT, are composed of protease inhibitors (eg, indinavir, atazanavir), xanthine, or dihydroxyadenine [32-35].
Dual-energy CT (DECT) may better characterize stone composition. DECT utilizes scanners that emit two separate radiograph energy sets to differentiate the attenuation properties of matter [36-40]. However, DECT is rarely used clinically to determine stone composition.
Ultrasound of the kidneys and bladder — Ultrasound of the kidneys and bladder reliably detects hydronephrosis and does not involve ionizing radiation. It is the preferred initial imaging modality in pregnant patients. In practice settings where low-radiation-dose CT scan technology is not available, ultrasound may represent a reasonable alternative to standard-dose CT of the abdomen and pelvis without contrast. This minimizes the cumulative radiation dose in patients undergoing multiple episodes of imaging for nephrolithiasis.
Ultrasound is less accurate and demonstrates greater variability than CT of the abdomen and pelvis without contrast for the diagnosis of nephrolithiasis (image 4). Pooled sensitivity and specificity of ultrasound is 0.70 (95% CI 0.67-0.73) and 0.75 (95% CI 0.73-0.78), respectively . Because CT detects nephrolithiasis not diagnosed with ultrasound, a CT is sometimes performed after a negative ultrasound to evaluate for a stone if the index of clinical suspicion remains high. Ultrasound is less accurate than CT at measuring stone size, stone number, and defining ureteral location. Thus, a positive ultrasound may lead to a follow-up CT to enable treatment planning.
Ultrasound has been compared with standard-dose abdominopelvic CT for diagnostic performance and cumulative population-level radiation dose. In a multicenter trial, 2759 emergency department patients clinically suspected to have nephrolithiasis were randomly assigned to initial imaging with a standard-dose, noncontrast CT ultrasound performed by a radiologist, or ultrasound performed at the bedside by an emergency clinician . After the initial imaging exam, subsequent evaluation and care was at the discretion of the treating clinicians. The key findings from this trial were as follows:
●The sensitivity of ultrasound for stone detection was 54 percent (if performed by an emergency clinician) and 57 percent (if performed by a radiologist). The sensitivity of CT was 88 percent. A CT scan was performed in 41 percent of patients who initially underwent ultrasound, whereas only 5 percent of patients who initially underwent CT subsequently underwent ultrasound.
●The cumulative radiation exposure after six months was approximately 70 percent higher with initial CT.
●The rate of important missed diagnoses resulting in complications, such as pyelonephritis with sepsis or diverticular abscess, were comparable between the two groups (0.5 percent with ultrasound versus 0.3 percent with CT). Serious adverse events and return visits to the emergency department after discharge were also similar.
Less frequently used tests — Abdominal radiography, IVP, and MRI are used as adjunct or follow-up examinations. They are rarely used in the initial diagnosis of nephrolithiasis. Digital tomosynthesis (DT) offers similar stone detection rates compared with noncontrast CT but is not yet routinely used in clinical practice for the diagnosis of nephrolithiasis.
Abdominal radiography — Abdominal radiography, also called abdominal plain x-ray, does not detect hydronephrosis and is less accurate than CT for stone detection and localization. The examination enables stone size measurements and is most often used either alone or in combination with ultrasound to follow patients being managed for nephrolithiasis.
Abdominal radiography detects 29 to 59 percent of stones seen on noncontrast CT [43,44]. Sensitivity depends on a number of factors including stone composition, location, and size, as well as patient body habitus and bowel contents. Large radiopaque stones such as calcium, struvite, and cystine stones are seen (image 5). Stones that are radiolucent and often missed on abdominal plain radiography include uric acid stones as well as small (<5 mm) stones (including small calcium-containing stones). False positives, such as phleboliths and vascular calcifications mistaken for kidney stones, also limit the specificity of the examination.
The effective radiation dose from a single abdominal radiograph is 0.8 mSv.
Intravenous pyelography — IVP, also called intravenous urography (IVU), involves radiographic imaging of the kidneys, ureters, and bladder before and after the administration of intravenous iodinated contrast. The examination reliably detects hydronephrosis but is less sensitive and specific than CT for the detection of stones. Noncontrast CT or ultrasound, where available, is recommended rather than IVP for the diagnosis of nephrolithiasis. IVP is used at some centers for the follow-up of ureteral calculi or the assessment of ureteral anatomy after stone removal.
The effective radiation dose from an IVP is 3 mSv.
Magnetic resonance imaging — MRI of the abdomen and pelvis, also called magnetic resonance urography (MRU), is rarely used for nephrolithiasis. Stones are poorly seen on MRI as they can only be detected as signal voids in the urine . Because the examination does not involve ionizing radiation, MRI is used to localize the obstruction in pregnant patients with hydronephrosis seen on ultrasound. Intravenous gadolinium contrast is usually not administered and should be avoided entirely in the pregnant patient. (See "Kidney stones in adults: Kidney stones during pregnancy".)
Digital tomosynthesis — DT is a high-resolution radiograph-based imaging technique that is routinely used in breast cancer screening. Although DT is not yet widely used in clinical practice for the diagnosis of nephrolithiasis, it has been shown to have similar stone detection rates compared with noncontrast CT and can be used for the follow-up of established stone disease. (See "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Digital breast tomosynthesis (DBT)' and 'Confirming stone passage' below.)
DT has been shown in small observational studies to be effective for the diagnosis and follow-up of nephrolithiasis [46-48]. In a study of 50 patients presenting with acute renal colic and hematuria who underwent both noncontrast CT and DT, DT detected 83 of the 86 stones (94 percent) detected by noncontrast CT . The mean effective radiation dose of DT was lower than that of both low-dose and standard-dose noncontrast CT (8.7 versus 13.2 and 51.0 Gycm2, respectively), and DT was found to be more cost effective than noncontrast CT. Another study showed that DT was an effective alternative to noncontrast CT for the follow-up of nephrolithiasis . Additional studies with larger populations are needed to confirm these findings.
The effective radiation dose from a DT is 0.9 mSv.
DIFFERENTIAL DIAGNOSIS — Several conditions may mimic flank pain caused by nephrolithiasis :
●Bleeding within the kidney can produce clots that lodge temporarily in the ureter. Thus, renal cell carcinoma can present with renal colic . By comparison, glomerular bleeding does not lead to clot formation or symptoms of renal colic. (See "Etiology and evaluation of hematuria in adults", section on 'Glomerular versus nonglomerular bleeding'.)
●Pyelonephritis frequently presents with flank pain, fever, and pyuria. Fever is uncommon in patients with uncomplicated stone disease. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults".)
●Pain due to an ectopic pregnancy can occasionally be mistaken for renal colic. The underlying cause of the pain can usually be clarified by obtaining a kidney and pelvic ultrasound [51,52]. (See "Ectopic pregnancy: Clinical manifestations and diagnosis".)
●Rupture or torsion of an ovarian cyst may present with flank pain. Such patients can usually be identified with ultrasound. (See "Evaluation and management of ruptured ovarian cyst".)
●Dysmenorrhea, which rarely presents with flank pain, begins just before or concurrent with the onset of menses. In the correct clinical setting, dysmenorrhea is diagnosed after other disorders are excluded. (See "Dysmenorrhea in adult females: Clinical features and diagnosis".)
●Patients with an aortic aneurysm are rarely misdiagnosed as having renal colic. (See "Clinical features and diagnosis of abdominal aortic aneurysm".)
●Acute intestinal obstruction, diverticulitis, or appendicitis may present with colic but usually not in association with hematuria. In addition, nausea and vomiting are characteristic of intestinal obstruction and renal colic, while abdominal tenderness is characteristic of diverticulitis and appendicitis but not nephrolithiasis. (See "Etiologies, clinical manifestations, and diagnosis of mechanical small bowel obstruction in adults" and "Clinical manifestations and diagnosis of acute colonic diverticulitis in adults" and "Acute appendicitis in adults: Clinical manifestations and differential diagnosis".)
●Biliary colic and cholecystitis can be associated with flank pain but usually not in association with hematuria. (See "Acute calculous cholecystitis: Clinical features and diagnosis".)
●Acute mesenteric ischemia rarely produces abdominal pain that can be confused with renal colic; in addition, mesenteric ischemia is often associated with metabolic acidosis but not hematuria. (See "Overview of intestinal ischemia in adults".)
●Herpes zoster may produce pain in the flank but is usually accompanied by a rash and not hematuria. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster".)
●Individuals seeking attention or narcotics may pretend to have renal colic and may have self-inflicted hematuria . In addition, there may be drug-seeking individuals who actually have kidney stones, but they are in the kidney and not obstructing.
Nephrolithiasis can usually be distinguished from the disorders listed above after a confirmatory radiologic test is performed (usually a noncontrast computed tomography [CT]). (See 'Diagnostic imaging' above.)
The differential diagnosis of abdominal discomfort is discussed elsewhere. (See "Causes of abdominal pain in adults".)
Triage of patients — Many patients with acute renal colic can be managed conservatively with pain medication and hydration until the stone passes (algorithm 1). In general, patients can be managed at home if they are able to take oral medications and fluids. Hospitalization is required for those who cannot tolerate oral intake or who have uncontrollable pain or fever. Urgent urologic consultation is warranted in patients with urinary tract infection, acute kidney injury, anuria, and/or unyielding pain, nausea, or vomiting [54,55]. (See 'Urologic consultation' below.)
Pain control — During an acute episode of renal colic, management is focused on pain control. Both nonsteroidal antiinflammatory drugs (NSAIDs) and opioids have traditionally been used for pain control in patients with acute renal colic. We suggest NSAIDs rather opioids as the initial choice for pain control in most patients presenting with acute renal colic. We reserve opioids for patients who have contraindications to NSAIDs, have severe kidney function impairment (ie, estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2), or do not achieve adequate pain relief with NSAIDs. (See "Prescription of opioids for acute pain in opioid naïve patients".)
We generally administer ketorolac to patients who present to the emergency department with renal colic. Treatment usually relieves symptoms within 10 to 30 minutes. Patients are then prescribed oral NSAIDs (eg, ibuprofen) for subsequent attacks that may occur while the patient is awaiting stone passage or surgical removal of the stone. In patients whose renal colic is being managed at home (rather than in the emergency department), some contributors to this topic give short-term oral NSAIDs if the patient is otherwise healthy, able to eat and drink, and voiding without difficulty, while other contributors prefer not to prescribe oral NSAIDs to outpatients until the patient has had an assessment of kidney function (eg, serum creatinine or eGFR). Patients who are managed as outpatients should be instructed to report to the emergency department if the pain does not resolve within four hours of the start of the pain. NSAIDs should be stopped three days before anticipated shock wave lithotripsy (SWL) to minimize the risk of bleeding.
Several meta-analyses have examined the efficacy of different analgesics used in the treatment of acute renal colic [56-58]. Collectively, these studies suggest that NSAIDs are at least as effective as opioids and other nonopioid medications and have a lower incidence of adverse effects (particularly nausea and vomiting) compared with opioids. As examples:
●In a 2018 systematic review and meta-analysis of 36 randomized controlled trials (4887 patients) that compared the efficacy and safety of NSAIDs (ketorolac, diclofenac, indomethacin, or tenoxicam) with that of opioids or paracetamol (acetaminophen) in the treatment of acute renal colic, NSAIDs were comparable to opioids or paracetamol in initial pain reduction at 30 minutes . Patients receiving NSAIDs had a lower requirement for rescue analgesia compared with those receiving opioids or paracetamol and were less likely to experience vomiting compared with those receiving opioids (relative risk [RR] 0.41, 95% CI 0.24-0.70). Similar findings were reported in an earlier systematic review .
●A 2015 Cochrane systematic review of 37 randomized or quasi-randomized trials (4483 patients) found that NSAIDs were more effective than placebo or antispasmodic agents in reducing pain by 50 percent within the first hour (RR 2.28, 95% CI 1.47-3.51) . Patients receiving NSAIDs were less likely to require rescue pain medication than those receiving placebo or antispasmodics (RR 0.35, 95% CI 0.20-0.60 and RR 0.34, 95% CI 0.14-0.84, respectively). The combination of NSAIDs and antispasmodics was not superior to NSAIDs alone for all assessed outcomes.
NSAIDs have the possible advantage of decreasing ureteral smooth muscle tone, thereby directly treating the mechanism by which pain is thought to occur (ureteral spasm) . In addition, treatment with NSAIDs discourages opioid-seeking patients who may spuriously present with symptoms of renal colic. On the other hand, in patients with preexisting kidney disease or severe volume depletion, NSAIDs may interfere with the kidney's autoregulatory response to acute obstruction and induce acute kidney injury. (See "NSAIDs: Acute kidney injury".)
Stone passage — The likelihood that ureteral stones will pass depends upon the size and location of the stone; smaller and more distal stones are more likely to pass without intervention [60-62].
Stone size is the major determinant of the likelihood of spontaneous stone passage, although stone location is also important [60-62]. Most stones ≤5 mm in diameter pass spontaneously. For stones larger than 5 mm in diameter, there is a progressive decrease in the spontaneous passage rate, which is unlikely with stones ≥10 mm in diameter. Proximal ureteral stones are also less likely to pass spontaneously (algorithm 1).
This was illustrated in a review of 75 patients with ureteral calculi, with the following observations :
●Among 41 patients with a stone diameter ≤2 mm, only two (5 percent) required intervention. The average time to stone passage in the remaining patients was 8.2 days, and 95 percent of stones passed in 31 days.
●Among 18 patients with a stone diameter between 2 and 4 mm, three (17 percent) required intervention. The average time to stone passage in the remaining patients was 12.2 days, and 95 percent of stones passed in 40 days.
●Among 16 patients with a stone diameter between 4 and 6 mm, eight (50 percent) required intervention. The average time to stone passage in the remaining patients was 22 days, and 95 percent of stones passed in 39 days.
Similar findings were noted in another report of 172 patients with ureteral stones . The likelihood of spontaneous stone passage was 87 percent for 1 mm stones, 76 percent of 2 to 4 mm stones, 60 percent for 5 to 7 mm stones, 48 percent for 7 to 9 mm stones, and 25 percent for stones ≥9 mm. Spontaneous passage was also affected by stone location, ranging from 48 percent for stones in the proximal ureter to 79 percent of stones at the ureterovesical junction.
Medical expulsive therapy — Several different medical expulsive therapies (MET) increase the passage rate of ureteral stones, including alpha blockers, calcium channel blockers, and antispasmodic agents, which have been used in combination with or without glucocorticoids [63-81].
In patients with ureteral stones >5 mm and ≤10 mm in diameter, we suggest treatment with the alpha blocker tamsulosin (0.4 mg once daily) for up to four weeks to facilitate spontaneous stone passage. If tamsulosin is not available, use of another alpha blocker (such as terazosin, doxazosin, alfuzosin, or silodosin) is reasonable. Although most evidence exists for distal ureteral stones, given the low side effect profile of alpha blockers, we choose to give alpha blockers to patients with stones >5 mm and ≤10 mm in any location of the ureter. Patients are then reimaged if spontaneous passage has not occurred (see 'Confirming stone passage' below). We do not administer an alpha blocker or any other form of MET in patients with ureteral stones ≤5 mm or >10 mm in diameter.
Our approach is based upon data suggesting higher rates of stone passage with alpha blockers versus conservative therapy alone, particularly among patients with ureteral stones >5 and ≤10 mm in diameter. As the cost of this treatment is low and significant side effects are uncommon, we believe that there is little downside to attempting MET with tamsulosin in such patients, provided that the patient has sufficient pain control and is without fever. We prefer alpha blockers to calcium channel blockers (eg, nifedipine), given data that suggest higher stone expulsion rates and faster stone passage with an alpha blocker . Routine use of other MET, such as tadalafil (a phosphodiesterase type 5 inhibitor) and glucocorticoids, is not recommended pending further data showing safety and efficacy.
Evidence for different MET is presented below:
●Alpha blockers – Several meta-analyses have shown that treatment with alpha blockers for up to four weeks, in addition to conservative therapy, may facilitate spontaneous stone passage [70,74,75,79,81,83,84]. As an example, in a 2018 meta-analysis of 67 trials that enrolled 10,509 patients, ureteral stone passage was significantly more likely with alpha blocker therapy than with conservative treatment alone (RR 1.45, 95% CI 1.36-1.55), although the beneficial effect was smaller among trials that compared alpha blocker therapy with a placebo control (RR 1.16, 95% CI 1.07-1.25) . Stone passage occurred an average of 3.4 days faster with alpha blocker therapy. In a subgroup analysis, alpha blocker therapy was less effective for stone clearance in patients with smaller stones (≤5 mm; RR 1.06) than in those with larger stones (>5 mm; RR 1.45); there were no differences in effectiveness based upon stone location or alpha blocker type. Although treatment with an alpha blocker did not significantly increase the risk of major adverse events (orthostatic hypotension, collapse, syncope, palpitations, or tachycardia) in the overall analysis, a slightly increased risk (RR 2.09, 95% CI 1.13-3.86) was seen with alpha blockers in the subset of placebo-controlled trials. Different alpha blockers appear to be similarly effective [71,85].
The value of these meta-analyses is emphasized given that the results of individual, large, randomized trials have been conflicting, with some studies questioning the efficacy of alpha blocker therapy as MET and others demonstrating benefit but only in patients with larger ureteral stones (between 5 and 10 mm) [73,77,78,86].
Alpha blocker therapy has been shown to be superior to the calcium channel blocker nifedipine as MET for distal ureteral stones. A meta-analysis of 12 randomized trials including 4961 patients that compared the efficacy and safety of tamsulosin and nifedipine for distal ureteral stones found higher rates of stone expulsion (RR 1.29, 95% CI 1.25-1.33), shorter expulsion times, and fewer complications (RR 0.45, 95% CI 0.28-0.72) with tamsulosin .
●Calcium channel blockers – Nifedipine has also been shown to facilitate stone passage  but is used less commonly. Studies directly comparing nifedipine with tamsulosin have reported lower stone passage rates, longer stone expulsion times, and more complications with nifedipine .
●Other agents – In addition to alpha blockers and nifedipine, tadalafil, a phosphodiesterase type 5 inhibitor, has been used alone or in combination with tamsulosin as MET [87-89]. In one trial, 285 patients with distal ureteral stones sized 5 to 10 mm in diameter were randomly assigned to tamsulosin (0.4 mg/day), silodosin (8 mg/day), or tadalafil (10 mg/day) until stone passage or for a maximum of four weeks . Rates of stone expulsion were highest for silodosin but were comparable between tamsulosin and tadalafil (83 versus 64 and 67 percent, respectively). Similarly, stone expulsion times were shortest for silodosin but similar between tamsulosin and tadalafil (15 versus 17 and 16 days, respectively).
Confirming stone passage — Clinicians should follow up with patients to confirm stone passage, as resolution of pain is not necessarily consistent with stone passage . In patients who have not passed their stone after four weeks of MET, we obtain imaging and refer to urology for potential intervention. (See 'Urologic consultation' below.)
The optimal approach to imaging in this setting is unclear, and practice varies among clinicians. Although noncontrast CT is the most sensitive imaging study to detect nephrolithiasis, its radiation exposure and cost make it a less attractive option as a follow-up imaging study. We prefer digital pelvic tomosynthesis paired with ultrasound of the kidneys and bladder to assess for ureteral stone resolution and ongoing hydronephrosis (see 'Digital tomosynthesis' above). Digital tomosynthesis (DT) has been shown to be an effective alternative to noncontrast CT for the follow-up of nephrolithiasis with the added benefits of lower radiation exposure and lower cost. If DT is not available, an alternative approach is to obtain an abdominopelvic radiograph paired with ultrasound of the kidneys and bladder to assess progression of a known radiopaque stone, or a noncontrast CT to assess progression of a known radiolucent stone .
Straining urine — Patients should be instructed to strain their urine for several days and bring in any stone that passes for analysis. This will enable the clinician to better plan preventive therapy. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on 'Stone analysis'.)
Treatment of urinary tract infection — Patients with evidence of a concurrent urinary tract infection should be promptly treated with antibiotics. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults".)
Urologic consultation — Urgent urologic consultation is warranted in patients with urinary tract infection, acute kidney injury beyond that expected from unilateral obstruction, anuria, and/or unyielding pain, nausea, or vomiting [3,91] (see 'Triage of patients' above). Outpatient urology referral is indicated in patients with a stone >10 mm in diameter and in patients who fail to pass the stone after a four-week trial of conservative management, including MET, particularly if the stone is >5 mm in diameter or if there is poorly controlled pain [62,92].
Current options for therapy of stones that do not pass include SWL, ureteroscopy (URS) with laser lithotripsy, percutaneous nephrolithotomy (PNL), and in rare cases, laparoscopic stone removal. Open surgical stone removal is rarely needed. Both URS and SWL may be considered first-line management options for ureteral stones that require removal. Multiple studies have documented that URS offers higher stone-free rates but with a slightly increased incidence of complications over SWL [15,93]. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones".)
For patients with larger kidney calculi (eg, >1.5 cm), kidney stones of harder composition (eg, cystine or calcium oxalate monohydrate), or stones in complex kidney or ureteral locations (eg, lower pole calyx or mid-ureter), endoscopic stone fragmentation with URS or PNL is preferred. (See "Kidney stones in adults: Surgical management of kidney and ureteral stones".)
SUBSEQUENT EVALUATION AND MANAGEMENT — Once the acute stone episode is over and the stone, if retrieved, is sent for analysis, the patient should be evaluated for possible underlying causes of stone disease. How and when this evaluation should be performed is discussed elsewhere. If the presenting event was the first episode of stone passage, the presence of other stones in the kidney demonstrate recurrent stone formation, and the patient should undergo further evaluation. (See "Kidney stones in adults: Evaluation of the patient with established stone disease".)
Subsequent therapy is based upon the type of stone and the biochemical abnormalities that are present. These issues are discussed in more detail elsewhere. (See "Kidney stones in adults: Prevention of recurrent kidney stones".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney stones".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Kidney stones in adults (The Basics)")
●Beyond the Basics topic (see "Patient education: Kidney stones in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Etiology – Eighty percent of patients with kidney stone disease (nephrolithiasis) form calcium stones. The other main types include uric acid, struvite and cystine stones. Individual stones may contain more than one type. (See 'Etiology' above.)
●Clinical manifestations – Although stones may pass asymptomatically, symptoms may occur when stones pass. The most common symptoms and signs are pain (renal colic or flank pain) and gross or microscopic hematuria. Other symptoms include nausea, vomiting, dysuria, and urinary urgency. Nephrolithiasis may lead to persistent kidney obstruction, which could cause permanent kidney damage if left untreated. (See 'Clinical manifestations' above.)
●Diagnosis – Nephrolithiasis should be suspected in patients presenting with renal colic or flank pain, with or without hematuria, particularly if the patient has a history of stone disease. Patients should undergo basic laboratory testing and imaging of the kidneys, ureters, and bladder to confirm the presence of a stone and assess for signs of urinary obstruction (eg, hydronephrosis) (algorithm 2). (See 'Laboratory testing' above and 'Diagnostic imaging' above.)
•Low-radiation-dose computed tomography (CT) of the abdomen and pelvis without contrast is the preferred examination for most adults as it reliably detects hydronephrosis and demonstrates the highest diagnostic accuracy for nephrolithiasis. CT also accurately describes stone size and location for treatment planning.
•If low-radiation-dose CT is not available, ultrasound of the kidneys and bladder, sometimes in combination with abdominopelvic radiography, is the second-line alternative. (See 'Selection of modality' above.)
●Differential diagnosis – Several conditions may mimic renal colic with or without hematuria. (See 'Differential diagnosis' above.)
●Acute management – Most patients with acute renal colic can be managed conservatively with pain medication and hydration until the stone passes (algorithm 1). Patients can be managed at home if they are able to take oral medications and fluids.
Hospitalization is required for those who cannot tolerate oral intake or who have uncontrollable pain or fever. (See 'Triage of patients' above.)
•Urologic consultation – Urgent urologic consultation is warranted in patients with urinary tract infection, acute kidney injury, anuria, and/or unyielding pain, nausea, or vomiting.
•Pain control – For most patients presenting with acute renal colic, we suggest nonsteroidal antiinflammatory drugs (NSAIDs) as initial therapy for pain control, rather than opioids or other therapies (Grade 2B). We reserve opioids for patients who have contraindications to NSAIDs, have severe kidney function impairment (ie, estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2), or do not achieve adequate pain relief with NSAIDs. (See 'Pain control' above.)
•Stone passage – Patients with stones >10 mm should be referred to urology for management.
Patients with stones ≤5 mm typically do not require specific treatment; most will pass spontaneously.
For patients with stones >5 and ≤10 mm in diameter, we suggest treatment with tamsulosin for up to four weeks to facilitate stone passage (Grade 2B). If tamsulosin is not available, use of another alpha blocker (such as terazosin, doxazosin, alfuzosin, or silodosin) is reasonable. Patients are then reimaged if spontaneous passage has not definitively occurred.
Patients who fail to pass the stone after a four-week trial of conservative or medical management (eg, tamsulosin) should be referred to urology, particularly if the stone is >5 mm in diameter or there is poorly controlled pain. (See 'Medical expulsive therapy' above and 'Confirming stone passage' above.)
•Straining urine – Patients should be instructed to strain their urine for several days and bring in any stone that passes for analysis. (See 'Straining urine' above.)
•Treatment of urinary tract infection – Patients with evidence of a concurrent urinary tract infection should be promptly treated with antibiotics. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults".)
●Subsequent evaluation and management – Once the acute stone episode is over and the stone, if retrieved, is sent for analysis, the patient should be evaluated for possible underlying causes of stone disease. (See 'Subsequent evaluation and management' above.)
4 : Randall's plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle.
6 : Apatite plaque particles in inner medulla of kidneys of calcium oxalate stone formers: osteopontin localization.
9 : Outcomes of long-term follow-up of asymptomatic renal stones and prediction of stone-related events.
10 : Derivation and validation of a clinical prediction rule for uncomplicated ureteral stone--the STONE score: retrospective and prospective observational cohort studies.
12 : Incidence of negative hematuria in patients with acute urinary lithiasis presenting to the emergency room with flank pain.
17 : Clinical effectiveness protocols for imaging in the management of ureteral calculous disease: AUA technology assessment.
18 : Unenhanced helical computed tomography vs intravenous urography in patients with acute flank pain: accuracy and economic impact in a randomized prospective trial.
20 : Benefits of CT urography in patients presenting to the emergency department with suspected ureteric colic.
22 : Low-dose and standard-dose unenhanced helical computed tomography for the assessment of acute renal colic: prospective comparative study.
23 : Low-dose nonenhanced helical CT of renal colic: assessment of ureteric stone detection and measurement of effective dose equivalent.
28 : Radiation dose reduction at multidetector CT with adaptive statistical iterative reconstruction for evaluation of urolithiasis: how low can we go?
31 : Relationship between duration of pain and secondary signs of obstruction of the urinary tract on unenhanced helical CT.
34 : Sensitivity and value of digital CT scout radiography for detecting ureteral stones in patients with ureterolithiasis diagnosed on unenhanced CT.
35 : Dual-energy CT for the characterization of urinary calculi: In vitro and in vivo evaluation of a low-dose scanning protocol.
36 : In vivo determination of urinary stone composition using dual energy computerized tomography with advanced post-acquisition processing.
38 : Renal stone assessment with dual-energy multidetector CT and advanced postprocessing techniques: improved characterization of renal stone composition--pilot study.
39 : Dual-energy computed tomography with advanced postimage acquisition data processing: improved determination of urinary stone composition.
40 : Targeted dual-energy single-source CT for characterisation of urinary calculi: experimental and clinical experience.
41 : The Accuracy and Prognostic Value of Point-of-care Ultrasound for Nephrolithiasis in the Emergency Department: A Systematic Review and Meta-analysis.
43 : Sensitivity of digital abdominal radiography for the detection of ureter stones by stone size and location.
44 : Ureteral calculi in patients with flank pain: correlation of plain radiography with unenhanced helical CT.
45 : Evaluation of acute renal colic: a comparison of non-contrast CT versus 3-T non-contrast HASTE MR urography.
47 : Digital Tomosynthesis: A Viable Alternative to Noncontrast Computed Tomography for the Follow-Up of Nephrolithiasis?
51 : Does this woman have an ectopic pregnancy?: the rational clinical examination systematic review.
56 : Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic.
57 : A Systematic Review and Meta-analysis Comparing the Efficacy of Nonsteroidal Anti-inflammatory Drugs, Opioids, and Paracetamol in the Treatment of Acute Renal Colic.
61 : Relationship of spontaneous passage of ureteral calculi to stone size and location as revealed by unenhanced helical CT.
63 : Editorial comment. The value of intensive medical management of distal ureteral calculi in an effort to facilitate spontaneous stone passage.
67 : Medical-expulsive therapy for distal ureterolithiasis: randomized prospective study on role of corticosteroids used in combination with tamsulosin-simplified treatment regimen and health-related quality of life.
68 : Randomized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol in medical expulsive therapy for distal ureteral calculi.
71 : The comparison and efficacy of 3 different alpha1-adrenergic blockers for distal ureteral stones.
72 : Adjuvant tamsulosin or nifedipine after extracorporeal shock wave lithotripsy for renal stones: a double blind, randomized, placebo-controlled trial.
73 : Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.
76 : Is there a role for tamsulosin in the treatment of distal ureteral stones of 7 mm or less? Results of a randomised, double-blind, placebo-controlled trial.
77 : Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial.
78 : Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.
79 : Effect of Tamsulosin on Stone Passage for Ureteral Stones: A Systematic Review and Meta-analysis.
82 : Comparative efficacy of tamsulosin versus nifedipine for distal ureteral calculi: a meta-analysis.
84 : What Is the Role ofα-Blockers for Medical Expulsive Therapy? Results From a Meta-analysis of 60 Randomized Trials and Over 9500 Patients.
85 : Prospective randomized trial comparing efficacy of alfuzosin and tamsulosin in management of lower ureteral stones.
87 : Tamsulosin versus tamsulosin plus tadalafil as medical expulsive therapy for lower ureteric stones: a randomized controlled trial.
88 : Role of tamsulosin, tadalafil, and silodosin as the medical expulsive therapy in lower ureteric stone: a randomized trial (a pilot study).
89 : Efficacy of Tamsulosin plus Tadalafil versus Tamsulosin as Medical Expulsive Therapy for Lower Ureteric Stones: A Randomized Controlled Trial.
90 : Resolution of Hydronephrosis and Pain to Predict Stone Passage for Patients With Acute Renal Colic.
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