Nephrolithiasis

Background

Nephrolithiasis is a common disease that is estimated to produce medical costs of

$2.1 billion per year in the United States.1 Nephrolithiasis specifically refers to
calculi in the kidneys, but this article discusses both renal calculi and ureteral calculi
(ureterolithiasis). Ureteral calculi almost always originate in the kidneys, although
they may continue to grow once they lodge in the ureter.

Urinary tract stone disease has been a part of the human condition for millennia; in
fact, bladder and kidney stones have even been found in Egyptian mummies. Some
of the earliest recorded medical texts and figures depict the treatment of urinary
tract stone disease.

Pathophysiology
Urinary tract stone disease is likely caused by two basic phenomena.

The first phenomenon is supersaturation of the urine by stone-forming constituents, including calcium,
oxalate, and uric acid. Crystals or foreign bodies can act as nidi, upon which ions from the supersaturated
urine form microscopic crystalline structures. The overwhelming majority of renal calculi contain calcium.
Uric acid calculi and crystals of uric acid, with or without other contaminating ions, comprise the bulk of
the remaining minority. Other, less frequent stone types include cystine, ammonium acid urate, xanthine,
dihydroxyadenine, and various rare stones related to precipitation of medications in the urinary tract. This
is likely the underlying cause of uric and cystine stones, but calcium-based stones (especially calcium
oxalate stones) likely have a more complex etiology.

The second etiology, which is most likely responsible for calcium oxalate stones, is deposition of stone
material on a renal papillary calcium phosphate nidus, typically a Randall plaque. Evan et al (2007)
recently proposed this model based on evidence accumulating from several laboratories.2 Calcium
phosphate precipitates in the basement membrane of the thin loops of Henle, erodes into the interstitium,
and then accumulates in the subepithelial space of the renal papilla. The subepithelial deposits, which
have long been known as Randall plaques, eventually erode through the papillary urothelium. Stone
matrix, calcium phosphate, and calcium oxalate gradually deposit on the substrate to create a urinary
calculus. Randall plaques are always composed of calcium phosphate.

History

• Patients with urinary calculi may report pain, infection, or hematuria. Small nonobstructing stones
in the kidneys only occasionally cause symptoms. If present, symptoms are usually moderate and
easily controlled.
• The passage of stones into the ureter with subsequent acute obstruction, proximal urinary tract
dilation, and spasm is associated with classic renal colic.
o Renal colic is characterized by undulating cramps and severe pain and is often
associated with nausea and vomiting.
o As the stone travels through the ureter, the pain moves from the flank to the lower
abdomen, down to the groin, and eventually to the scrotal or labial areas.
 o Associated irritative bladder symptoms are common when the stone is located in the
distal or intramural ureter.
• Patients with large renal stones known as staghorn calculi are often relatively asymptomatic.
o Staghorn refers to the presence of a branched kidney stone occupying the renal pelvis
and at least one calyceal system. Such calculi usually manifest as infection and
hematuria rather than as acute pain.
o Asymptomatic bilateral obstruction, which is uncommon, manifests as symptoms of renal
failure.
• Important historical features are as follows:
o Duration, characteristics, and location of pain
o History of urinary calculi
o Prior complications related to stone manipulation
o Urinary tract infections
o Loss of renal function
o Family history of calculi
o Solitary or transplanted kidney
o Chemical composition of previously passed stones

Physical

• Dramatic costovertebral angle tenderness is common; this pain can move to the upper or lower
abdominal quadrant as a ureteral stone migrates distally.
• Peritoneal signs are usually absent—an important consideration in distinguishing renal colic from
other sources of flank or abdominal pain.
• Findings should correlate with the reports of pain, so that complicating factors (eg, urinary
extravasation, abscess formation) can be detected.
• Beyond this, the specific location of tenderness does not always correlate with the exact location
of the stone, although the calculus is often in the general area of maximum discomfort.

Causes

• Most research on the etiology and prevention of urinary tract stone disease has been directed
toward the role of elevated urinary levels of calcium, oxalate, and uric acid in stone formation, as
well as reduced urinary citrate levels.
• Hypercalciuria is the most common metabolic abnormality. Some cases of hypercalciuria are
related to increased intestinal absorption of calcium (associated with excess dietary calcium
and/or overactive calcium absorption mechanisms), some are related to excess resorption of
calcium from bone (ie, hyperparathyroidism), and some are related to an inability of the renal
tubules to properly reclaim calcium in the glomerular filtrate (renal-leak hypercalciuria).
• Magnesium and especially citrate are important inhibitors of stone formation in the urinary tract.
Decreased levels of these in the urine predispose to stone formation.
• A low fluid intake, with a subsequent low volume of urine production, produces high
concentrations of stone-forming solutes in the urine. This is an important, if not the most
important, environmental factor in kidney stone formation.
• The exact nature of the tubular damage or dysfunction that leads to stone formation has not been
characterized.
 • The most common findings on 24-hour urine studies include
hypercalciuria, hyperoxaluria, hyperuricosuria,hypocitraturia, and low urinary volume. Other
factors, such as high urinary sodium and low urinary magnesium concentrations, may also play a
role. To identify these risk factors, a 24-hour urine profile, including appropriate serum tests of
renal function, uric acid, and calcium, is needed. Such testing is available from various
commercial laboratories. A finding of hypercalcemia should prompt follow-up with an intact
parathyroid hormone study to evaluate for primary and secondary hyperparathyroidism.

Laboratory Studies

• Urinalysis
o Evaluate the urine for evidence of hematuria and infection. Approximately 85% of
patients with urinary calculi exhibit gross or microscopic hematuria.
o An absence of hematuria does not rule out urinary calculi; in fact, approximately 15% of
patients with urinary stones do not exhibit hematuria.
• Complete blood cell count
o In the context of nephrolithiasis, an elevated white blood cell count suggests renal or
systemic infection.
o A depressed red blood cell count suggests a chronic disease state or severe ongoing
hematuria.
• Serum electrolytes, creatinine, calcium, uric acid, parathyroid hormone (PTH), and phosphorus
studies
o These are needed to assess a patient's current renal function and to begin the
assessment of metabolic risk for future stone formation.
o A high serum uric acid level may indicate gouty diathesis or hyperuricosuria, while
hypercalcemia suggests either renal-leak hypercalciuria (with secondary
hyperparathyroidism) or primary hyperparathyroidism.
o If the serum calcium level is elevated, serum PTH levels should be obtained.
• Twenty-four–hour urine collection for levels of pH, calcium, oxalate, uric acid, sodium,
phosphorus, citrate, magnesium, creatinine, and total volume
o This study is designed to provide more information about the exact nature of the chemical
problem that caused the stone. This information is useful not only to allow more specific
and effective therapy for stone prevention but also to identify patients with renal calculi
who might have other significant health problems. Keep in mind that all of the 24-hour
urine chemistry findings may be within the reference range in patients who actively form
stones and who are at high risk for stones. In these cases, optimizing the levels is
beneficial.
o The following are objective indications for a metabolic evaluation with a 24-hour
urinalysis:
 Residual calculi after surgical treatment
 Initial presentation with multiple calculi
 Initial presentation before age 30 years
 Renal failure
 Solitary kidney (including renal transplant)
 Family history of calculi
 More than one stone in the past year
 Bilateral calculi
  Patient preference: An important consideration in determining whether to perform
a 24-hour urine study is the patient's interest. If a patient is strongly motivated to
follow a protracted stone-prevention treatment plan (involving diet, supplements,
medications, or a combination), obtain the study. If a patient is unlikely or
unwilling to follow a long-term treatment plan, a metabolic evaluation is probably
unwarranted. Patients have to understand that stone disease is a chronic
disease. If they do not commit to helping themselves in behavior modification,
dietary changes, or medical compliance, they are prone to more frequent calculi
formation.
o Calcium, oxalate, and uric acid
 Elevation of the 24-hour excretion rate of any of these 3 components indicates a
predisposition to form calculi.
 Hypercalciuria can be subdivided into absorptive, resorptive, and renal-leak
categories based on the results of blood tests and 24-hour urinalysis on both
regular and calcium-restricted diets.
 Depending on the specific subtype, the treatment of absorptive
hypercalciuria may include modest dietary calcium restriction, thiazide
diuretics, oral calcium binders, or phosphate supplementation.
 Resorptive hypercalciuria is primary hyperparathyroidism and requires
parathyroidectomy, when possible. If parathyroid surgery is not possible,
phosphate supplementation is usually recommended.
 Renal-leak hypercalciuria, which is less common than absorptive
hypercalciuria, is usually associated with secondary hyperparathyroidism
and is best managed with thiazide diuretics.
 Another clinical approach to hypercalciuria when hyperparathyroidism has been
excluded with appropriate blood tests is avoidance of excessive dietary calcium
(usual recommendation, 600-800 mg/d), modest limitation of oxalate intake, and
thiazide therapy. If thiazide therapy fails, additional workup (eg, calcium-loading
test, more thorough evaluation) may be needed.
 Indiscriminate dietary calcium restriction is not advantageous and in fact may
increase formation of calculi owing to a secondary increase in oxalate absorption.
The reduced dietary calcium reduces the oxalate-binding sites in the
gastrointestinal tract, increasing the free dietary oxalate and leading to increased
oxalate absorption. The final product of this is a net increase in stone production.
 Hyperoxaluria may be primary (a rare genetic disease), enteric (due to
malabsorption and associated with chronic diarrhea or short-bowel syndrome), or
idiopathic. Oxalate restriction and vitamin B-6 supplementation are somewhat
helpful in patients with idiopathic hyperoxaluria. Enteric hyperoxaluria is the type
that is most amenable to treatment; dietary calcium supplementation often
produces dramatic results.
 Calcium citrate is the recommended supplement because citrate tends to further
reduce stone formation. Calcium carbonate supplementation is less expensive
but does not provide citrate's added benefit. Calcium therapy works as an oxalate
binder, reducing oxalate absorption from the intestinal tract. Calcium should be
administered with meals, especially those that contain high-oxalate foods. The
supplement should not contain added vitamin D because this increases calcium
absorption, leaving less calcium in the intestinal tract to bind to oxalate. The
optimal 24-hour urine oxalate level is 20 mg/d or less.
  Hyperuricosuria predisposes to the formation of calcium-containing calculi
because sodium urate can produce malabsorption of macromolecular inhibitors
or can serve as a nidus for the heterogeneous growth of calcium oxalate crystals.
Gouty diathesis, a condition of increased stone production associated with high
serum uric acid levels, is also possible. Therapy involves potassium citrate
supplementation, allopurinol, or both. In general, patients with pure uric acid
stones and hyperuricemia are treated with allopurinol, and those with
hyperuricosuric calcium stones are treated with citrate supplementation. The
optimal 24-hour urine uric acid level is 600 mg/d or less.
o Sodium and phosphorus
 Excess sodium excretion can contribute to hypercalciuria by a phenomenon
known as solute drag. Elevated urinary sodium levels are almost always
associated with dietary indiscretions. Decreasing the oral sodium intake can
decrease calcium excretion, thereby decreasing calcium saturation.
 An elevated phosphorus level is useful as a marker for a subtype of absorptive
hypercalciuria known as renal phosphate leak (absorptive hypercalciuria type III).
Renal phosphate leak is identified by high urinary phosphate levels, low serum
phosphate levels, high serum 1,25 vitamin D-3 (calcitriol) levels, and
hypercalciuria. This type of hypercalciuria is uncommon and does not respond
well to standard therapies.
 The above laboratory tests are confirmatory but are performed only if the index of
clinical suspicion is high. Any patient with hypercalciuria who has a low serum
phosphorus level and a high-normal or high urinary phosphorus level may have
this condition. Repeat laboratories along with a 1,25 vitamin D-3 level are
confirmatory. Phosphate supplements are used to correct the low serum
phosphate level, which then decreases the inappropriate activation of vitamin D
originally caused by the hypophosphatemia. This corrects the hypercalciuria,
which is ultimately a vitamin D–dependent function in this condition.
o Citrate and magnesium
 Magnesium and, especially, citrate are important chemical inhibitors of stone
formation. Hypocitraturia is one of the most common metabolic defects that
predispose to stone formation, and some authorities have recommended citrate
therapy as primary or adjunctive therapy to almost all patients who have formed
recurrent calcium-containing stones. Many laboratories use 24-hour urine citrate
levels of 320 mg/d as the normal threshold, but optimal levels are probably closer
to the median level (640 mg/d) in healthy individuals. Periodic monitoring of pH
with special FDA-approved dipsticks (StoneGard II fromwww.uridynamics.com)
can be very useful to titrate and optimize potassium citrate supplementation. A
pH level of 6.5 is usually considered optimal. A pH level over 7.0 should be
discouraged, as it prompts calcium phosphate precipitation.
 Liquid or powder pharmacologic citrate preparations are recommended when
absorption is a problem or in cases involving chronic diarrhea. Sustained-release
tablets are available and may be more convenient for some patients.
Concentrates of lemon juice provide an excellent source of citrate, or,
alternatively, large quantities of lemonade can be ingested, which, of course, has
the added benefit of providing increased fluid intake.
 Potassium citrate is the preferred type of pharmacologic citrate supplement,
although a potassium/magnesium preparation is under investigation.
  Magnesium is a more recently recognized inhibitor of stone formation, and the
clinical role of magnesium replacement therapy is less well defined than that of
citrate.
o Creatinine
 Creatinine is the control that allows verification of a true 24-hour sample. Most
individuals excrete 1-1.5 g of creatinine daily.
 Values at either extreme that are not explained by estimates of lean body weight
should prompt consideration that the sample is inaccurate.
o Total volume
 Patients in whom stones form should strive to achieve a urine output of more
than 2 L daily in order to reduce the risk of stone formation.
 Patients with cystine stones or those with resistant cases may need a daily
urinary output of 3 L for adequate prophylaxis.
o pH: Some stones, such as those composed of uric acid or cystine, are pH-dependent,
meaning that they can form only in acidic conditions. Calcium phosphate and struvite only
form when the urine pH is alkaline. Although the other parameters in the 24-hour urine
usually identify patients at risk of forming these stones, pH studies can be important in
monitoring these patients, in optimizing therapy with citrate supplementation, and in
identifying occult stone disease in some patients.

Imaging Studies

• Plain abdominal radiography

o Plain abdominal radiography (also known as a flat plate or kidney, ureter, and bladder
[KUB] radiography) is useful for assessing total stone burden, as well as the size, shape,
and location of urinary calculi in some patients. It is also helpful in determining the
progress of the stone without the need for more expensive tests with greater radiation
exposures.
o Calcium-containing stones (approximately 85% of all upper urinary tract calculi) are
radiopaque, but pure uric acid, indinavir-induced, and cystine calculi are relatively
radiolucent on plain radiography.
o When used with other imaging studies, such as a renal ultrasonography or, particularly,
CT scanning, the plain film helps provide a better understanding of the size, shape,
location, orientation, and composition of urinary stones revealed with these other imaging
studies. This may also be helpful in planning surgical therapy and in tracking progress of
the stone over time.
• Renal ultrasonography
o Renal ultrasonography by itself is frequently adequate to determine the presence of a
renal stone. The study is mainly used alone in pregnancy or in combination with plain
abdominal radiography to determine hydronephrosis or ureteral dilation associated with
an abnormal radiographic density believed to be a urinary tract calculus.
o A stone easily identified with renal ultrasonography but not visible on the plain radiograph
may be a uric acid or cystine stone, which is potentially dissolvable with urinary
alkalinization therapy.
o Ureteral calculi, especially in the distal ureter, and stones smaller than 5 mm are not
easily observed with ultrasonography.
• Intravenous urography
 o An intravenous urography (IVU) test, also known as an intravenous pyelography (IVP),
has been the standard for determining the size and location of urinary calculi up until
recently. IVU provides both anatomical and functional information.
o IVU is very labor intensive and is no longer the standard for the initial evaluation of a
patient with a kidney stone. It may fail to reveal alternative pathology if a stone is not
discovered, delaying the final diagnosis.
 Up to 6 hours may be required to complete the study in the presence of severe
obstruction.
 For optimal results, IVU requires a bowel preparation.
 It involves intravenous injection of potentially allergic and mildly nephrotoxic
contrast material.
o A helical CT scan without contrast material is currently believed to be the best initial
radiographic examination for acute renal colic. If positive, KUB radiography is
recommended to assist in follow-up and planning.
o The so-called delayed nephrogram on the IVU is one of the hallmark signs of acute
urinary tract obstruction. The relative delay in penetration of intravenous contrast passing
through an obstructed kidney elicits this sign. The kidney appears to develop a whitish
color, and contrast appearance within the collecting system of the affected renal unit is
significantly delayed.
o IVU is helpful in identifying the specific problematic stone among numerous pelvic
calcifications and in establishing that the other kidney is functional. These determinations
are particularly helpful if the degree of hydronephrosis is mild and the non-contrast CT
scan findings are not definitive. CT scanning with delayed contrast series and thin slices
has reduced the need for IVU in the evaluation of problematic ureteral stones.
• Helical CT scanning without contrast material
o Technological advances in CT scanning allow imaging of the entire abdomen in a single
breath hold.
o When performed with thin slices and without intravenous contrast material, CT scanning
is the most sensitive clinical imaging modality for calcifications. Even calculi that are
radiolucent on a plain radiograph (except for indinavir-induced stones) are clear and
distinct on a CT scan.
o Contrast is not used in the initial screening study because it makes the entire urinary
collecting system appear white on the study, thus masking the stones.
o CT scanning with contrast, obtained after the noncontrast study, is useful in treatment
planning and in distinguishing problematic radio-opacities.
o At most institutions that offer this examination, CT scanning has replaced IVU for the
assessment of urinary tract stone disease, especially for acute renal colic.
o Adding plain radiography to noncontrast CT scanning increases the value of the study by
allowing visualization of the size, shape, and relative position of the stone. The "scout"
reconstruction of the CT scan, formatted to look like a plain radiograph, is not nearly as
sensitive as a good plain radiograph in detecting calculi; however, if the stone is visible
on the "scout" reconstruction, only plain radiography may be needed later to determine if
the stone has moved or passed.
o A lucent stone that is not visible on the KUB radiograph that is clearly visible on the CT
scan may indicate a uric acid calculus. This suggests a different diagnosis and therapy
(allopurinol and/or urinary alkalinization) than for a calcium stone. For these reasons,
many institutions routinely perform KUB radiography whenever renal colic noncontrast
 CT scanning is performed. The Hounsfield unit density of the calculus on CT scanning
can also be useful in predicting whether the stone is composed of uric acid.
o Advantages of a CT scanning include the following:
 It can reveal other pathology (eg, abdominal aneurysms, appendicitis,
cholecystis).
 It can be performed quickly.
 It avoids the use of intravenous contrast materials.
o Disadvantages of CT scanning include the following:
 It cannot be used to assess individual renal function.
 It can fail to reveal some unusual radiolucent stones, such as those caused by
indinavir, which are invisible on the CT scan. Because of this possibility, IVUs
with contrast should be used for patients taking indinavir.
 It is relatively expensive.
 It exposes the patient to a relatively high radiation dose.
 Precise identification of small distal stones is occasionally difficult.
 It is not suitable for tracking the progress of the stone over time, supporting the
recommendation for KUB radiography along with the CT scan.
• Plain renal tomography
o Although largely replaced by helical CT scanning without contrast, plain renal
tomography is often helpful in finding small stones in the kidneys, especially in patients
who are large or obese whose bowel contents complicate observation of any renal
calcifications.
o Tomography does not require extensive preparation and can be performed quickly. In
addition, the cost and radiation dosage to the patient are less than with CT scanning.
o Plain renal tomography is most useful when monitoring a difficult-to-observe stone after
therapy or for clarification of stones not clearly detected or identified with other studies.
o Plain renal tomography is also useful for determining the number of stones present in the
kidneys before a stone-prevention program is instituted. This information is used to better
differentiate stones formed before therapy began from those formed later.

Treatment

Medical Care
The first part of this section discusses emergency management of renal (ureteral) colic. The second part
addresses the issues of medical therapy for stone disease. Medical therapy for stone disease takes both
short- and long-term forms (the former to dissolve the stone [possible only with noncalcium stones] and
the latter to prevent further stone formation). Stone prevention should be considered most strongly in
patients who have risk factors for increased stone activity, including stone formation before age 30 years,
family history of stones, multiple stones at presentation, renal failure, and residual stones after surgical
treatment.

• General guidelines for emergency management

o After diagnosing renal (ureteral) colic, determine the presence or absence of obstruction
or infection.
o Obstruction in the absence of infection can be initially managed with analgesics and with
other medical measures to facilitate passage of the stone. Infection in the absence of
 obstruction can be initially managed with antimicrobial therapy. In either case, promptly
refer the patient to a urologist.
o If neither obstruction nor infection is present, analgesics and other medical measures to
facilitate passage of the stone (see below) can be initiated with the expectation that the
stone will likely pass from the upper urinary tract if its diameter is smaller than 5-6 mm
(larger stones are more likely to require surgical measures).
o If both obstruction and infection are present, emergent decompression of the upper
urinary collecting system is required (see Surgical Care). Immediately consult with a
urologist for patients whose pain fails to respond to ED management.
• Specific guidelines for emergency management
o Although the role of supranormal hydration in the management of renal (ureteral) colic is
controversial, patients who are dehydrated or ill need adequate restoration of circulating
volume.
o The cornerstone of ureteral colic management is analgesia, which can be achieved most
expediently with parenteral narcotics or nonsteroidal anti-inflammatory drugs (NSAIDs).
 Morphine sulfate is the narcotic analgesic drug of choice for parenteral use.
 Ketorolac tromethamine is the only NSAID approved for parenteral use in the
United States, and it is often effective when used for renal colic. It is also now
available as an intranasal spray for moderate-to-severe pain.
 Antiemetic agents such as metoclopramide HCl and prochlorperazine may also
be added as needed.
 If oral intake is tolerated, the combination of oral narcotics (eg, codeine,
oxycodone, hydrocodone, usually in a combination form with acetaminophen),
NSAIDs, and antiemetics, as needed, is a potent outpatient management
approach for renal (ureteral) colic.
o The traditional outpatient treatment approach detailed above has recently been improved
with the application of active medical expulsive therapy (MET). Although NSAIDs have
ureteral-relaxing effects and, as such, can be considered a form of MET, patient
outcomes have been significantly improved only with the use of more potent (off-label)
medications. Many randomized trials have confirmed the efficacy of MET in reducing the
pain of stone passage, increasing the frequency of stone passage, and reducing the
need for surgery. MET should be considered in any patient with a reasonable probability
of stone passage. Stones smaller than 3 mm are already associated with an 85% chance
of spontaneous passage, and, as such, MET is probably most useful for stones 3-10 mm
in size. Overall, MET is associated with a 65% greater likelihood of stone passage.
 The initially popularized regimens for MET included corticosteroids such as
prednisone. Although corticosteroids are effective, concerns about their side
effects (admittedly not supported by randomized data) limited the acceptance of
MET. More recently, randomized studies have demonstrated great efficacy of the
individual agents below, sparing the corticosteroid component.
 The calcium channel blocker nifedipine relaxes ureteral smooth muscle and
enhances stone passage.
 The alpha-blockers, such as terazosin, and the alpha-1 selective blockers, such
as tamsulosin, also relax musculature of the ureter and lower urinary tract,
markedly facilitating passage of ureteral stones. Some literature suggests that
the alpha-blockers are more effective in this setting than the calcium channel
blockers.
  MET with calcium channel blockers and alpha-blockers also appear to improve
the results of extracorporeal shock-wave lithotripsy (Extracorporeal shockwave
lithotripsy) inasmuch as the stone fragments resulting from treatment appear to
clear the system more effectively.
o Analgesic therapy combined with MET dramatically improves the passage of stones,
addresses pain, and reduces the need for surgical treatment. A typical regimen for this
aggressive management is 1-2 oral narcotic/acetaminophen tablets every 4 hours as
needed for pain, 600-800 mg ibuprofen every 8 hours, and MET with 30 mg nifedipine
extended-release tablet once daily, 0.4 mg tamsulosin once daily, or 4 mg of terazosin
once daily. Limit MET to a 10- to 14-day course, as most stones that pass during this
regimen do so in that time frame. If outpatient treatment fails, promptly consult a
urologist.
• Long-term medical treatment of calcium-containing urinary calculi
o Urinary calculi composed predominantly of calcium cannot be dissolved with current
medical therapy; however, medical therapy is important in the long-term
chemoprophylaxis of further calculus growth or formation.
o Prophylactic therapy might include limitation of dietary components, addition of stone-
formation inhibitors or intestinal calcium binders, and, most importantly, augmentation of
fluid intake.
o Besides advising patients to avoid excessive salt and protein intake and to increase fluid
intake, base medical therapy for the chronic chemoprophylaxis of urinary calculi on the
results of a 24-hour urinalysis for chemical constituents.
• Uric acid and cystine calculi
o Uric acid and cystine calculi can be dissolved with medical therapy. Patients with uric
acid stones who do not require urgent surgical intervention for reasons of pain,
obstruction, or infection can often have their stones dissolved with alkalization of the
urine.
o Sodium bicarbonate can be used as the alkalizing agent, but potassium citrate is usually
preferred because of the availability of slow-release tablets and the avoidance of a high
sodium load.
o The dosage of the alkalizing agent should be adjusted to maintain the urinary pH
between 6.5 and 7.0. Urinary pH of more than 7.5 should be avoided because of the
potential deposition of calcium phosphate around the uric acid calculus, which would
make it undissolvable. Both uric acid and cystine calculi form in acidic environments.
o Even very large uric acid calculi can be dissolved in patients who comply with therapy.
Roughly 1 cm per month dissolution can be achieved.
o Practical ability to alkalinize the urine significantly limits the ability to dissolve cystine
calculi. Chemoprophylaxis of uric acid and cystine calculi consists primarily of long-term
alkalinization of urine.
o If hyperuricosuria or hyperuricemia is documented in patients with pure uric acid stones
(present in only a relative minority), allopurinol (300 mg qd) is recommended because it
reduces uric acid excretion.
o Pharmaceuticals that can bind free cystine in the urine (eg, D-penicillamine, 2-alpha-
mercaptopropionyl-glycine) help reduce stone formation in cystinuria. Therapy should
also include long-term urinary alkalinization and aggressive fluid intake. Captopril has
been shown to be effective in some trials, although, again, strong data are lacking.
Routine use should be avoided but can be added in patients who have difficulty in
dissolving and preventing cystine stones.
Surgical Care

• The primary indications for surgical treatment include pain, infection, and obstruction.
Additionally, certain occupational and health-related reasons exist.
• General contraindications to definitive stone manipulation include the following:
o Active, untreated urinary tract infection
o Uncorrected bleeding diathesis
o Pregnancy (a relative, but not absolute, contraindication)
• Specific contraindications may apply to a given treatment modality. For example, do not perform
ESWL if a ureteral obstruction is distal to the calculus or in pregnancy.
• For an obstructed and infected collecting system secondary to stone disease, virtually no
contraindications exist for emergency surgical relief either by ureteral stent placement (a small
tube placed endoscopically into the entire length of the ureter from the kidney to the bladder) or
by percutaneous nephrostomy (a small tube placed through the skin of the flank directly into the
kidney). Urologists place ureteral stents in the operating room while patients are under
anesthesia; interventional radiologists or urologists perform percutaneous nephrostomies in the
clinic or radiology suite while patients are under local anesthesia.
o Many urologists prefer one or the other, but, in general, patients who are acutely ill, who
have significant medical comorbidities, or who harbor stones that probably cannot be
bypassed with ureteral stents undergo percutaneous nephrostomy, while others receive
ureteral stent placement.
o Infection combined with urinary tract obstruction is an extremely dangerous situation, with
significant risk of urosepsis and death, and must be treated emergently in virtually all
cases.
• The vast majority of symptomatic urinary tract calculi are now treated with noninvasive or
minimally invasive techniques, while open surgical excision of a stone from the urinary tract is
now limited to isolated atypical cases.
• In general, stones that are 4 mm in diameter or smaller will probably pass spontaneously, and
stones that are larger than 8 mm are unlikely to pass without surgical intervention. With MET,
stones 5-8 mm in size often pass, especially if located in the distal ureter. The larger the stone,
the lower the possibility of spontaneous passage, although many other factors determine what
happens with a particular stone.
• Guidelines are now available to assist the urologist in selecting surgical treatments. The 2005
American Urological Association staghorn calculus guidelines recommend percutaneous
nephrostolithotomy as the cornerstone of management.In the ureteral stone guidelines produced
by a joint effort of the American Urological Association and the European Association of Urology,
ESWL and ureteroscopy are both recognized as first-line treatments for ureteral stones.
o Extracorporeal shockwave lithotripsy
 Most urinary tract calculi that require treatment are currently managed with this
ESWL, which is the least invasive of the surgical methods of stone removal. This
modality was once believed to be a panacea. Unfortunately, much of the
literature has exposed the weaknesses of newer-generation lithotriptors. As a
result, ESWL success rates are not as good as they once were.
 The patient, under varying degrees of anesthesia (depending on the type of
lithotriptor used), is placed on a table or in a gantry that is then brought into
contact with the shock head. The deeper the anesthesia (general endotracheal),
the better the results. In addition, evidence is mounting that slower shockwave
 delivery (60-80 per minute) improves the results. New lithotriptors that have two
shock heads, which deliver a synchronous or asynchronous pair of shocks
(possibly increasing efficacy), have attracted great interest.
 The shock head delivers shockwaves developed from an electrohydraulic,
electromagnetic, or piezoelectric source. The shockwaves are focused on the
calculus, and the energy released as the shockwave impacts the stone produces
fragmentation. The resulting small fragments pass in the urine.
 ESWL is limited somewhat by the size and location of the calculus. A stone
larger than 1.5 cm in diameter or one located in the lower section of the kidney is
treated less successfully. Fragmentation still occurs, but the large volume of
fragments or their location in a dependent section of the kidney precludes
complete passage. In addition, results may not be optimal in large patients,
especially if the skin-to-stone distance exceeds 10 cm.14
o Ureteroscopy
 Ureteroscopic manipulation of a stone, depicted in the image below, is the next
most commonly applied modality. A small endoscope, which may be rigid,
semirigid, or flexible, is passed into the bladder and up the ureter to directly
visualize the stone.
 The typical patient has acute symptoms caused by a distal ureteral stone, usually
measuring 5-8 mm. This calculus can be rapidly addressed with miniaturized
instruments. A stone can be either directly extracted using a basket or grasper or
broken into small pieces using various lithotrites (eg, laser, ultrasonic,
electrohydraulic, ballistic).
 Often, a ureteral stent must be placed following this procedure in order to prevent
obstruction from ureteral spasm and edema. A ureteral stent is often
uncomfortable; consequently, many urologists eschew stent placement following
ureteroscopy in selected patients.
o Percutaneous nephrostolithotomy
 Percutaneous nephrostolithotomy allows fragmentation and removal of large
calculi from the kidney and ureter and is often used for the many ESWL failures.
A needle, and then a wire, over which is passed a hollow sheath, are inserted
directly in the kidney through the skin of the flank.
 Percutaneous access to the kidney typically involves a sheath with a 1-cm
lumen. Relatively large endoscopes with powerful and effective lithotrites can be
used to rapidly fragment and remove large stone volumes.
 Because of their increased morbidity compared with ESWL and ureteroscopy,
percutaneous procedures are generally reserved for large and/or complex renal
stones and failures from the other two modalities.
 In some cases, a combination of ESWL and a percutaneous technique is
necessary to completely remove all stone material from a kidney. This technique,
called sandwich therapy, is reserved for staghorn or other complicated stone
cases. In such cases, experience has shown that the final procedure should be
percutaneous nephrostolithotomy.

Consultations
 • Immediate consultation with a urologist is recommended in cases of both infection and
obstruction associated with urinary calculi.
• Consultation with a urologist is required when immediate ED management of renal (ureteral) colic
fails.
• Referral to a urologist is necessary for all stones that prove refractory to outpatient management
or that fail to pass spontaneously.

Diet

• In almost all patients in whom stones form, an increase in fluid intake and, therefore, an increase
in urine output is recommended. This is likely the single most important aspect of stone
prophylaxis.
• The only other general dietary guidelines are to avoid excessive salt and protein intake.
Moderation of calcium and oxalate intake is also reasonable, but great care must be taken not to
indiscriminately instruct the patient to reduce calcium intake. Excessive dietary calcium restriction
can increase the risk of calcium oxalate stone formation (see below).
• Dietary calcium should not be restricted beyond normal unless specifically indicated based on 24-
hour urinalysis findings. Urinary calcium levels are normal in many patients with calcium stones.
Reducing dietary calcium in these patients may actually worsen their stone disease, because
more oxalate is absorbed from the gastrointestinal tract in the absence of sufficient intestinal
calcium to bind with it. This results in a net increase in oxalate absorption and hyperoxaluria,
which tends to increase new kidney stone formation in patients with calcium oxalate calculi. An
empiric restriction of dietary calcium may also adversely affect bone mineralization and may have
osteoporosis implications, especially in women. This practice should be condemned unless
indicated based on a metabolic evaluation.
• As a rule, dietary calcium should be restricted to 600-800 mg/d in patients with diet-responsive
hypercalciuria who form calcium stones. This is roughly equivalent to a single high-calcium or
dairy meal per day.

Medication

The medications listed below are those used in the ED and in outpatient management of renal (ureteral)
colic; they do not include antibiotics.

Opioid analgesics
These agents are used for pain relief.

Morphine sulfate (Astramorph, Duramorph)

DOC for parenteral use in the immediate management of pain due to renal (ureteral) colic.

Adult
2-5 mg IV q15min (limited by RR <16 bpm and systolic BP <100 mm Hg) prn for pain relief

Pediatric
Not established
Precautions

Concurrent therapy to address nausea, emesis, and urinary retention may be required; these are
common in patients with renal (ureteral) colic and can be exacerbated by morphine

Oxycodone and acetaminophen (Percocet)

Drug combination indicated for oral relief of moderate to severe pain.

Adult
1-2 tab or cap PO q4-6h prn

Pediatric
Not established

Precautions
Duration of action may increase in elderly patients; be aware of patients' total daily dose of
acetaminophen; doses higher than maximum (4 g/d) may cause liver toxicity; caution when patients have
severe renal or hepatic dysfunction; administer with caution in patients dependent on opiates because
this substitution may result in acute opiate withdrawal symptoms

Hydrocodone and acetaminophen (Vicodin)

Drug combination indicated for oral relief of moderate to severe pain.

Adult

1-2 tab or cap PO q4-6h prn

Pediatric

Not established

Precautions

Duration of action may increase in elderly patients; be aware of patients' total daily dose of
acetaminophen; doses higher than maximum (4 g/d) may cause liver toxicity; caution when patients have
severe renal or hepatic dysfunction; caution in patients dependent on opiates because substitution may
result in acute opiate withdrawal symptoms

Nonsteroidal anti-inflammatory drugs

These agents inhibit pain and inflammatory reactions by decreasing activity of cyclooxygenase, which is
responsible for prostaglandin synthesis. Both properties are beneficial in the management of renal
(ureteral) colic.

Ketorolac (Toradol)

Only NSAID approved for parenteral use in adults in the United States. Onset of action is evident within
10 min.

Adult

30 mg IV initially (15 mg if >65 y, renal impairment, or <50 kg body weight), followed by 15 mg IV q6h prn
Pediatric

Not established

Precautions

Should be avoided in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia,
interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients
with preexisting renal disease or compromised renal perfusion; prolonged dosing associated with
increased incidence GI bleed (especially in elderly patients); caution in presence of congestive heart
failure, hypertension, hepatic dysfunction, or anticoagulant therapy

Ketorolac intranasal (Sprix)

NSAID; inhibits cyclo-oxygenase (COX), an early component of the arachidonic acid cascade, resulting in
reduced synthesis of prostaglandins, thromboxanes, and prostacyclin. Elicits anti-inflammatory, analgesic,
and antipyretic effects. Indicated for short-term (up to 5 d) management of moderate to moderately severe
pain. Bioavailability of 31.5-mg intranasal dose (2 sprays) is approximately 60% of 30-mg IM dose.
Intranasal spray delivers 15.75 mg per 100-µL spray; each 1.7-g bottle contains 8 sprays.

Adult
<65 years: 31.5 mg (ie, 1 spray in each nostril) q6-8h; not to exceed 126 mg/d
<50 kg or >65 years: 15.75 mg (ie, 1 spray in only 1 nostril) q6-8h; not to exceed 63 mg/d

Pediatric
<17 years: Not established

Precautions
Store refrigerated until use, then may keep at room temperature during use; discard bottle within 24 h
after first dose, even if bottle still contains medication (will not deliver intended dose after 24 h); may lead
to new onset of hypertension or may exacerbate existing hypertension; NSAIDs may cause serious skin
reactions (eg, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis); common
local adverse effects include mild and transient nasal discomfort and irritation

Ibuprofen (Motrin, Advil)

Oral NSAID for outpatient management.

Adult

600-800 mg PO q8h

Pediatric

Not established

Precautions

Caution in patients with congestive heart failure, hypertension, and decreased renal and hepatic function;
caution in anticoagulation abnormalities or during anticoagulant therapy

Corticosteroids
These are strong anti-inflammatory agents that reduce ureteral inflammation. They also have profound
metabolic and immunosuppressive effects.

Prednisone (Deltasone, Orasone, Sterapred)

Only a short course of therapy (5-10 d) should be administered.

Adult

10 mg PO bid

Pediatric

Not established

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis,
myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis,
growth suppression, and infections may occur with glucocorticoid use

Calcium channel blockers

These agents are smooth-muscle relaxants that can facilitate ureteral stone passage.

Nifedipine (Procardia)

This antihypertensive agent facilitates the passage of ureteral stone. Extended-release formulation
simplifies treatment and encourages compliance. Only short-term therapy (10 d) should be considered for
this indication.

Adult

30 mg/d PO extended-release cap

Pediatric

Not established

Precautions

May cause lower extremity edema; allergic hepatitis has occurred (rare)

Alpha blockers
These agents are smooth-muscle relaxants that can facilitate ureteral stone passage.

Tamsulosin (Flomax)

This alpha-1 selective blocker is indicated for the treatment of lower urinary tract symptoms due to
prostatic enlargement. An off-label use, as discussed above, is to facilitate passage of ureteral stones.
Only short-term therapy (10 d) should be considered for this indication.

Adult

0.4 mg tab PO qd
Pediatric

Not established

Precautions

Not for use as antihypertensive drug; may cause orthostasis; avoid situations that may result in injuries if
syncope occurs; rule out presence of carcinoma or cancer before initiating treatment

Terazosin (Hytrin)

This alpha blocker is indicated for the treatment of hypertension, as well as lower urinary tract symptoms
due to prostatic enlargement. An off-label use is to facilitate passage of ureteral stones. Only short-term
therapy (10 d) should be considered for this indication.

Adult
4 mg PO qd, although, in some patients, an increasing dose (2, 4, 8 mg) may be considered

Pediatric
Not established

Precautions
Caution in renal impairment; may cause marked hypotension following first dose and coadministration
with beta-blockers

Uricosuric agents
These agents help prevent nephropathy and recurrent calcium oxalate calculi.

Allopurinol (Zyloprim)

Inhibits xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine. Reduces the
synthesis of uric acid without disrupting the biosynthesis of vital purines.

Adult
200-600 mg PO qd

Pediatric
<10 years: 10 mg/kg/d PO divided bid/tid, not to exceed 800 mg/d
>10 years: 200-600 mg/d PO qd

Precautions
Not for use in asymptomatic hyperuricemia; reduce dose in renal insufficiency; monitor liver function and
obtain CBC counts before initiating therapy and periodically thereafter

Alkalinizing agents, oral

These agents are used for the treatment of metabolic acidosis and when long-term maintenance of
alkaline urine is desirable.
Potassium citrate (Polycitra-K, Urocit K)

Polycitra-K is a pleasant-tasting oral systemic alkalizer that contains potassium citrate and citric acid in a
sugar-free base. Each unit dose packet contains potassium citrate monohydrate 3300 mg and citric acid
monohydrate 1002 mg. Each unit dose packet, when reconstituted, supplies the same amount of active
ingredients as is contained in 15 mL (1 tablespoonful) Polycitra-K oral solution, provides 30 mEq
potassium ion, and is equivalent to 30 mEq bicarbonate.
Urocit K is a wax matrix tab that contains potassium citrate. Many patients prefer the Urocit K tabs to
Polycitra-K. These tabs come in 5-mEq and 10-mEq sizes; the latter is a large pill and, for that reason,
some patients better tolerate the 5-mEq tab. The patient should be warned that the tabs pass through into
the feces intact.
Absorbed and metabolized to potassium bicarbonate, thus acting as a systemic alkalizer. Effects are
essentially those of chlorides before absorption and those of bicarbonates subsequently. Oxidation is
virtually complete so that <5% of the potassium citrate is excreted in the urine unchanged. Highly
concentrated and, when administered after meals and before bedtime, allows maintenance of an alkaline
urinary pH at all times, usually without necessity of 2 am dose. In recommended dosage, alkalinizes urine
without producing systemic alkalosis. Available as syrups and crystals. All forms should be taken with
water or juice according to directions.

Adult
30-90 mEq/d PO divided tid/qid with food

Pediatric
10-40 mEq/d PO divided tid/qid with food

Precautions
Monitoring of serum electrolyte levels is recommended; caution in CHF, hypertension, edema, or any
condition sensitive to sodium or potassium intake; conversion of citrate to bicarbonate in liver may be
blocked in severe illness, shock, hepatic failure associated with GI distress; high plasma concentrations
may cause death due to cardiac depression, arrhythmias, or arrest