Chapter 94: Urologic Stone Disease

Emergency medicine management is directed at relieving pain, assessing kidney function, and determining the likelihood of spontaneous stone passage. This chapter discusses renal and ureteral stones. Bladder stones are discussed in chapter 92, "Acute Urinary Retention."

The prevalence of kidney stones in the United States has risen from 5.2% in 1994¹ to 8.8% in 2010.² The prevalence is 10.6% in men and 7.1% in women.² Increasing prevalence is documented in Europe and Southeast Asia.³ Obesity and diabetes are strongly associated with kidney stones.² The lifetime risk is approximated at 10% to 15% in the United States and other developed countries. Urinary calculi recur in 37% of patients in the first year, 50% of patients within 10 years, and 75% of patients in 20 years.⁴ Children <16 years old constitute about 7% of all renal stone cases.⁵ Unique to children is a 1:1 sex distribution.⁴ The most common causes in children involve metabolic abnormalities (50%), urologic anomalies (20%), infection (15%), immobilization syndrome (5%), and idiopathic causes (10%).⁵ Ethnically, whites develop stones more frequently than blacks.²

Stone formation requires supersaturation of dissolved salts in the urine, which condense into a solid phase. Increasing the amount of solvent (urine) and decreasing the amount of solute presented to the kidney (i.e., calcium, oxalate, uric acid) can aid in prevention. Inhibitory substances, such as citrate, and magnesium can prevent crystal precipitation and stone formation.

About 80% of calculi are composed of calcium oxalate, calcium phosphate, or a combination of both. Calcium excretion is elevated in conditions that include hyperparathyroidism, absorptive and renal hypercalciuria, and immobilization syndrome. Randall's plaque, a collection of interstitial suburothelial calcium phosphate particles on the surface of the renal papillae, serves as a nucleation surface for calcium oxalate stones.^6,7 Complex interactions between the gut, kidney, and bones contribute to calcium oxalate stone formation. A diet restricting calcium paradoxically increases calcium stone formation because there is less calcium to bind oxalate in the intestinal lumen, leading to increased absorption of oxalate from the gut, recruitment of calcium from bones, osteoporosis, and symptomatic stone disease in predisposed patients.

About 10% of stones are struvite (magnesium-ammonium-phosphate). These stones are associated with infection by urea-splitting bacteria (Proteus, Klebsiella, Staphylococcus species, Providencia, and Corynebacterium) and are the most common cause of staghorn calculi, which are large stones that form a cast of the renal pelvis. Antibiotic penetration into staghorn calculi is poor, and the potential for urosepsis exists as long as the stones remain.

Uric acid causes about 10% of urolithiasis. Twenty-five percent of patients with gout will develop kidney stones, and they occur at a rate of approximately 1% per year after the first gout attack. Urate stones are radiolucent, and the urine is typically acidic. Cystine stones are rare, account for approximately 1% of all stones, and occur in patients with cystinuria, an autosomal recessive genetic disorder affecting amino acid transport (COLA: cysteine, ornithine, lysine, arginine). Stones can be made of many other miscellaneous substances, including indinavir, triamterene, xanthene, and silicate.

Some medications predispose to stone disease. The protease inhibitor indinavir sulfate, used to treat the human immunodeficiency virus, is associated with a 4% to 10% incidence of symptomatic urolithiasis. Pure indinavir stones are radiolucent on plain abdominal x-ray and CT scan. Carbonic anhydrase inhibitors, triamterene, and laxative abuse also increase the prevalence of renal stones.⁸ With appropriate evaluation, 90% of patients will have a cause identified, and over 50% of calcium oxalate stone recurrences can be prevented.⁹ Table 94-1 lists risk factors associated with kidney stones.^2,3,10

Pain associated with kidney stones is due to obstruction of a hollow viscus organ (ureter) and subsequent hydronephrosis creating pressure against Gerota's fascia, causing flank pain. Isolated small renal pelvis stones (not staghorn) do not cause pain unless they cause intermittent obstruction of the entrance to the ureter. A migrating but nonobstructive stone also causes pain. During acute obstruction, most patients have no rise in serum creatinine because the unobstructed kidney functions at up to 185% of its baseline capacity. A rise in serum creatinine in acute obstruction suggests a solitary kidney or preexisting renal disease such that the unobstructed kidney is unable to compensate completely. Fortunately, most patients have incomplete ureteral obstruction, and many patients can be safely observed over weeks. Irreversible renal damage from an obstructive kidney stone is rare if obstruction has been present for ≤1 month.¹¹

The probability of spontaneous passage of stones is determined by multiple factors, including size, shape, location, and degree of ureteral obstruction. Bizarre or irregularly shaped stones with spicules or sharp edges have a lower spontaneous passage rate. With complete obstruction, there is a lower rate of spontaneous passage than if the blockage is partial. The most common sites of obstruction include the ureteropelvic junction, where the 1-cm pelvis constricts into the 2- to 3-mm ureter; the pelvic brim, where the ureter courses over both the pelvis and the iliac vessels; and finally, the ureterovesical junction, because this is the most constricted site of the ureter due to the muscular coat of the bladder. Based on stone size alone, 98% of stones <5 mm will pass within 4 weeks without intervention. Sixty percent of stones 5 to 7 mm and 39% of stones >7 mm will pass within 4 weeks. Stone size on plain radiographs is magnified by up to 20%, and a measured stone on CT is 88% of actual stone size.¹²

The classic symptom complex for nephrolithiasis is the acute onset of a crampy intermittent flank pain that radiates toward the groin. As pain originates from a hollow viscus (ureter), the pain is visceral in nature without associated peritoneal irritation. Patients writhe in pain, unable to find a position of comfort. However, patients with renal colic may demonstrate rebound tenderness (29%), guarding (61%), and rigidity (8%).¹³ Pain is commonly accompanied by nausea and vomiting (50%). The adrenergic response to pain can result in tachycardia, hypertension, and diaphoresis. Hematuria is present in only 85% of patients with renal colic, and 30% have gross hematuria.

The location of the pain correlates somewhat with the location of the stone. Stones in the upper ureter refer pain to the flank, whereas those in the mid-ureter radiate to the lower anterior quadrant of the abdomen. A distal ureter stone, which is where 75% of stones are diagnosed, refers pain to the groin. Stones positioned at the ureterovesical junction can mimic a urinary tract infection by causing frequency, urgency, and dysuria in 3% to 24% of patients.¹³ Extracorporeal shock wave lithotripsy fractures stones into small particles with the use of focused sound waves. The resulting "sludge" is passed in the urine. When there are large fragments, an acute episode of renal colic occurs.

In children, symptoms vary with age. Older children are more likely to present with typical adult symptoms. Younger children may complain of nonspecific abdominal or pelvic pain. Although renal colic is rare in infants, symptoms may be mistakenly attributed to intestinal colic. Overall, 20% to 30% of children may have only painless hematuria with urologic stone disease.

During the patient interview, elucidate three important items of history: assess risk factors for stone development (Table 94-1), prior stone-related outcome, and important mimickers. The risk factors for a poor outcome with stones include three categories: renal function at risk, history of difficulty with stones, and infection (Table 94-2). Two mimickers that are very important to exclude are abdominal aortic aneurysm and renal artery infarction. Nephrolithiasis is the most common misdiagnosis given to patients with a rupturing or expanding abdominal aortic aneurysm. Recall that stones do not usually present in men older than age 60 and do not cause hypotension, even transiently. Renal artery thrombosis can mimic stone symptoms due to swelling of the infarcted kidney and can also be associated with hematuria. However, early in the course, noncontrast CT will not necessarily show inflammation around the kidney, and because no contrast is used, the function of the kidney is not assessed.

The diagnosis of urologic stone disease is clinically suspected and supported by the presence of hematuria; imaging confirms the diagnosis with certainty.

Many diagnoses can be confused with renal colic (Table 94-3). History and physical examination can be difficult because the patient's discomfort may interfere with adequate information collection. The most critical diagnoses to consider are aortic dissection and ruptured abdominal aortic aneurysm. Renal colic and abdominal aortic aneurysm may have similar presentations.

LABORATORY EVALUATION

The laboratory evaluation centers on evaluating for infection, kidney dysfunction, and possibility of pregnancy. Test all females of childbearing potential for pregnancy when considering renal colic. With pregnancy, consider ectopic pregnancy in the differential diagnosis while minimizing radiation exposure to the fetus.

Urinalysis is needed to rule out infection. If infection is found, obtain urine culture and sensitivities to guide antibiotic therapy.¹⁴ In suspected pediatric nephrolithiasis, a culture is often sent regardless, because identification of a urinary tract infection in children can be more difficult (see chapter 132, "Urinary Tract Infection in Infants and Children").

Hematuria (three or more red blood cells per high-power field), or even its absence, can mislead the physician. Although 10% to 15% of patients with nephrolithiasis will have no hematuria, approximately 24% of patients with flank pain and hematuria have no radiographic evidence of ureterolithiasis.¹⁵ Therefore, although hematuria may contribute to diagnostic decision making, it should not be used alone to exclude or confirm the diagnosis of ureterolithiasis¹⁵ (see chapter 91, "Urinary Tract Infections and Hematuria").

Check renal function because the overwhelming majority of patients who form stones have reduced creatinine clearance.¹⁶ Unless febrile or systemically ill, a WBC count does not aid in the evaluation; many patients will have an elevated WBC count due to stress demargination. Other laboratory studies, such as serum calcium or uric acid, are not useful in the initial evaluation or treatment but help determine stone type and long-term therapy.

IMAGING

Imaging confirms the presence of a ureteral stone, rules out other diagnoses, identifies complications, defines stone location, and assists with management if the stone fails to pass spontaneously.¹⁷ Imaging is recommended by the American Urological Association in patients with suspected first-time stones.¹⁸ For young, healthy, stable patients with a history of kidney stones in whom the diagnosis is clinically clear, imaging may be deferred until the follow-up visit provided that a reliable follow-up mechanism exists.¹⁹ However, clinicians are frequently incorrect in their clinical impression in 20% to 70% of cases.²⁰ CT scanning reveals an alternative diagnosis in 33% of the patients.²⁰ Thus, the physician should determine the need for confirmation of the diagnosis based on the patient's past medical history, dangers of accumulated radiation exposure, clarity of the clinical diagnosis, and ease of follow-up and ability to return for worsening symptoms.

CT

The noncontrast helical CT scan is sensitive and specific, with "diagnostic" positive and negative likelihood ratios for detection of renal stones (Table 94-4).²¹ Images are obtained from the top of the kidney to the bladder base. Secondary signs of ureteral obstruction, such as ureteral dilatation, stranding of perinephric fat, dilatation of the collecting system, and renal enlargement, can be helpful in making the diagnosis. In combination, unilateral ureteral dilatation and perinephric stranding have a positive predictive value of 96% for stone disease.²² If both are absent, the negative predictive value is 93% to 97%²² (Figures 94-1 and 94-2).

Noncontrast helical CT has advantages over other imaging modalities, including superior speed, the avoidance of radiocontrast media, and greater ability to identify other pathologies. However, because radiocontrast is not used, the specificity and sensitivity for other diagnoses (e.g., abdominal aortic aneurysm, appendicitis, renal infarct, or perinephric abscess) are not as great as with imaging protocols using contrast, and renal function is not assessed.

Low-dose CT has been studied in small numbers. Low-dose CT is as sensitive as standard CT in detecting stones >3 mm in patients with a body mass index <30. However, it was not as sensitive for smaller stones or at higher body mass indices.²³

IV Urography

IV urography (or IV pyelogram) is rarely used, but yields information on renal function and anatomy. It detects calculi with modest sensitivity but excellent specificity²¹ (Table 94-4). IV urography can be an adjunct to CT if functional information and knowledge of the degree of obstruction are required.

Plain Abdominal Radiographs

Approximately 90% of urinary calculi are radiopaque because calcium phosphate and calcium oxalate stones have a density similar to that of bone. Magnesium-ammonium-phosphate (struvite) is slightly less radiodense, followed by cystine, which is only partly radiopaque. Uric acid and matrix stones are essentially radiolucent, as are most stones associated with medications such as indinavir. Unfortunately, because of small size and overlapping soft tissue and bone shadows, urinary stones are visible much less frequently on plain films. A plain kidney-ureter-bladder film is neither sensitive nor specific enough to rule in or rule out stone. However, once the location of a stone is identified on CT scan, the progression of the stone can be followed by a kidney-ureter-bladder film assuming the stone is visible.

US

If patients are not candidates for CT due to concerns about radiation (e.g., during pregnancy or in children), US can assist in the diagnosis. Although useful in the detection of larger stones (Figure 94-3), US may miss smaller (<5 mm in diameter) ureteral stones.²⁴ US is helpful in diagnosing stones in the proximal and distal ureters but is insensitive for mid-ureteral stones. Overall, US has only modest sensitivity and specificity for detecting renal stones (Table 94-4) but is 78% sensitive for detecting hydronephrosis. This sensitivity for hydronephrosis goes up from 75% for stones <6 mm to 90% for stones >6 mm. However, of hydronephrosis diagnosed by US, up to 22% of studies do not represent obstruction; but rather, normal anatomic variation, full bladder, and renal cysts. Rapid bolus infusion of crystalloid can result in a false-positive finding of hydroureter.

US provides information on renal size and, with Doppler scanning, renal blood and urine flow. Obesity may interfere with obtaining good-quality scans, and US can miss early obstructive signs. Accuracy of the US study is dependent on the skill and experience of the operator.

Bedside US

Although not quite as accurate as a screening examination would need to be, compared with CT, bedside US by ED physicians had a sensitivity of 80% (95% confidence interval [CI], 65% to 89%), specificity of 83% (95% CI, 61% to 94%), and overall accuracy of 81% (95% CI, 69% to 89%) in the detection of hydronephrosis.^25,26,27 Bedside US may be useful to detect larger stones unlikely to respond to conservative measures.

PAIN AND NAUSEA

Treatment for symptomatic nephrolithiasis in the ED includes pain and nausea/vomiting control as needed, antibiotics for those with evidence of infection, and medical expulsion therapy. Forced IV hydration results in no difference in pain control or stone passage rates when compared to minimal IV hydration.²⁸ Fluids should be given to correct any fluid deficit due to vomiting or limited oral intake.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary choice of analgesics in the treatment of stone disease, because they have a direct action on the ureter by inhibiting prostaglandin synthesis.^29,30 IV administration achieves more rapid relief than IM or PO dosing³¹ (e.g., ketorolac, 30 milligrams IV). There are several U.S. Food and Drug Administration boxed warnings regarding NSAID use: do not give NSAIDS in those with aspirin or NSAID hypersensitivity; avoid in coagulopathy or patients at risk for bleeding; NSAIDS increase risk of GI bleeding at any time during therapy and without warning; and avoid in renal impairment. Urology may delay the use of lithotripsy on patients who receive any drugs affecting platelet function for 3 to 10 days. Narcotics (e.g., hydromorphone, 0.5 to 2.0 milligrams IV) are good analgesics but do not affect the cause of pain. Because both the pain of the stone and narcotics can cause nausea and vomiting, address these symptoms as well.

Metoclopramide is the only antiemetic that has been specifically studied in the treatment of renal colic. In two double-blinded studies, metoclopramide provided pain relief equivalent to narcotic analgesics in addition to relieving nausea. Metoclopramide works by blocking dopaminergic receptors in the CNS but is less sedating than other centrally acting dopamine antagonists.³²

URINARY TRACT INFECTION

Patients with fever, renal insufficiency, and systemic signs of infection are treated with IV antibiotics and admitted. Options include gentamicin or tobramycin, 3.0 milligrams/kg/d divided every 8 hours, plus ampicillin, 1 to 2 grams every 4 hours; piperacillin-tazobactam, 3.375 grams IV every 6 hours; cefepime, 2 grams IV every 8 hours; ticarcillin-clavulanic acid, 3.1 grams every 6 hours; or ciprofloxacin, 400 milligrams every 12 hours, if local sensitivities do not predict treatment failure.

Patients who have a ureteral stone with an associated urinary tract infection but no evidence of significant obstruction, fever, or systemic illness can be treated as outpatients, provided follow-up in 48 to 72 hours can be accomplished (see section "Disposition and Follow-Up" later in the chapter). The choice of antibiotic should cover gram-negative rods and be appropriate for antibiotic sensitivity at your institution. Resistance rates of >10% to 20% should preclude use of that antibiotic. Choices include ciprofloxacin, 500 milligrams PO twice a day for 10 to 14 days; levofloxacin, 500 milligrams PO once a day for 10 to 14 days; cefpodoxime, 200 milligrams PO twice a day for 10 to 14 days; or others predicted to be successful based on local sensitivities.

MEDICAL EXPULSION THERAPY

Medical expulsion therapy is commonly used in clinical practice and is recommended by the urologic societies.^33,34 α-Blockers are associated with increased rate of expulsion, decreased time to expulsion, and decreased pain, with a number needed to treat of 3.3 and a 2- to 6-day improvement in time to expulsion.^33,35 The benefit shown is attributable to stones in the distal third of the ureter because these were the ones most commonly included in the studies. The most commonly used agent is tamsulosin (0.4 milligram PO daily for up to 4 weeks), but terazosin (5 to 10 milligrams daily) and doxazosin (4 milligrams daily) are also as effective.^33,35 Renal colic is an off-label use of these agents; 4% of patients develop side effects including hypotension, but the drugs generally appear to be well tolerated. Calcium channel blockers, specifically nifedipine (30 milligrams PO daily up to 8 weeks), have adverse effects in approximately 15% of patients, a number needed to treat of 3.9, and time to stone expulsion reported as <28 days.³³ Some studies, including one that involved primarily ED patients, have called into question the benefit of this therapy.^36,37 One double-blinded study showed that there was no benefit in stones <6 mm.³⁸ Steroids are not currently recommended.³⁴

Most patients with stones are discharged with urologic or primary care follow-up, at which time preventive therapy may be considered based on stone type.¹⁸ Because of lower rates of spontaneous passage, discuss disposition of patients with large (>5 mm), irregular, or proximal stones (Table 94-5). Also discuss with urology the disposition of patients with renal insufficiency, severe underlying comorbidities, complete obstruction, multiple ED visits associated with the stone, or associated urinary tract infection without sepsis.

Discharge is appropriate in patients with smaller stones, in the absence of infection, and when pain is controlled by oral analgesics. Give patients a urinary strainer with instructions to save any stones they pass for pathologic evaluation. Average time for stone passage varies according to size and location but may range up to 7 to 30 days for stones 5 to 6 mm in diameter. Patients should be counseled to return promptly for fever, vomiting, or uncontrolled pain. A prescription for an oral opiate and NSAIDs should be provided, as well as for medical expulsive therapy if used. Follow-up with a urologist within 7 days should be recommended.

If the stone passes in the ED, no further treatment is required. Elective urologic consultation is recommended so that the etiology of the stone is evaluated and a prophylactic strategy can be arranged. Patients with hematuria, negative imaging studies, and no other source require outpatient urologic follow-up to determine the cause of hematuria.

PREGNANCY

Stones occur in 1 in 1500 pregnancies, and 80% to 90% present in the second or third trimester. The presentation is the same as in nonpregnant patients with flank pain (89%) and hematuria (95%). The study of choice in pregnancy is US to identify hydronephrosis. Unfortunately, up to 90% of pregnant patients display physiologic hydronephrosis. US techniques recommended to improve sensitivity and diagnostic accuracy include endovaginal approach and looking for ureteral jets and calculating resistive indices for the kidneys.³⁹ If US does not provide the information necessary for management, low-dose CT^40,41 or MRI⁴² should be considered in consultation with a urologist and obstetrician. The radiation doses for various imaging modalities for stones are as follows: kidney-ureter-bladder, 0.05 to 0.15 cGy; three-film IV pyelogram, 0.15 to 0.20 cGy; and CT scan, 2.2 to 2.5 cGy.⁴² The American College of Obstetrics recognizes the use of CT scan in the evaluation of emergent conditions in pregnancy, including nephrolithiasis.⁴³

With regard to treatment of pregnant patients, NSAIDS are not recommended, so narcotic pain control is most commonly used. Medical expulsive therapy with α-blockers, which are category B drugs in pregnancy, is acceptable.⁴¹

CHILDREN

Children with stones need investigation for metabolic disease and anatomic abnormality. Up to 30% of children with kidney stones have urinary tract anomalies. CT scans are most commonly used to identify stones in the pediatric ED, although radiation exposure remains a concern. US evaluation should be considered, especially in patients with a history of stones. Treatment includes pain and nausea control. Medical expulsive therapy is not recommended in children.

PRACTICE GUIDELINES

Practice guidelines have been issued by the European Association of Urology³⁴ (www.uroweb.org/gls/pdf/21_Urolithiasis_LR.pdf) and the American Urological Association (http://www.auanet.org/education/clinical-practice-guidelines.cfm).