NEPHROLITHIASIS

Introduction
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, shown below, and ureteral calculi (ureterolithiasis). Ureteral calculi almost always originate in the kidneys, although they may continue to grow once they lodge in the ureter.

Small renal calculus that would likely respond to...
Small renal calculus that would likely respond to extracorporeal shockwave lithotripsy.

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Small renal calculus that would likely respond to...

Small renal calculus that would likely respond to extracorporeal shockwave lithotripsy.

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, depicted below, is likely caused by two basic phenomena.

Distal ureteral stone observed through a small, r...
Distal ureteral stone observed through a small, rigid ureteroscope prior to ballistic lithotripsy and extraction. The small caliber and excellent optics of today's endoscopes greatly facilitate minimally invasive treatment of urinary stones.

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Distal ureteral stone observed through a small, r...

Distal ureteral stone observed through a small, rigid ureteroscope prior to ballistic lithotripsy and extraction. The small caliber and excellent optics of today's endoscopes greatly facilitate minimally invasive treatment of urinary stones.

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.
Frequency
United States

The lifetime prevalence of urinary tract stone disease in the United States is approximately 10%. The annual incidence of urinary tract stones in the industrialized world is estimated to be 0.2%. The likelihood that a white male will develop stone disease by age 70 years is 1 in 8. Stones of the upper urinary tract are more common in the United States than in the rest of the world. Roughly two million patients present on an outpatient basis with stone disease each year in the United States, which is a 40% increase from 1994.1
International

The incidence of urinary tract stone disease in developed countries is similar to that in the United States. Stone disease is rare in only a few areas, such as Greenland and the coastal areas of Japan. In developing countries, bladder calculi are more common than upper urinary tract calculi; the opposite is true in developed countries. These differences are believed to be diet-related.
Mortality/Morbidity

* The morbidity of urinary tract calculi is primarily due to obstruction with its associated pain, although nonobstructing calculi can still produce considerable discomfort.
* Conversely, patients with obstructing calculi may be asymptomatic, which is the usual scenario in patients who experience loss of renal function due to chronic untreated obstruction.
* Stone-induced hematuria is frightening to the patient but is rarely dangerous by itself.
* The most morbid and potentially dangerous aspect of stone disease is the combination of urinary tract obstruction and upper urinary tract infection. Pyelonephritis, pyonephrosis, and urosepsis can ensue. Early recognition and immediate surgical drainage are necessary in these situations.

Race

Urinary tract calculi are far more common in Asians and whites than in Native Americans, Africans, African Americans, and some natives of the Mediterranean region. Although some differences may be attributable to geography (stones are more common in hot and dry areas) and diet, heredity also appears to be a factor. This is suggested by the finding that, in regions with both white and nonwhite populations, stone disease is much more common in whites.
Sex

* In general, urolithiasis is more common in males (male-to-female ratio of 3:1).
* Stones due to discrete metabolic/hormonal defects (eg, cystinuria, hyperparathyroidism) and stone disease in children are equally prevalent between the sexes.
* Stones due to infection (struvite calculi) are more common in women than in men.

Age

* Most urinary calculi develop in persons aged 20-49 years.
* Patients in whom multiple recurrent stones form usually develop their first stones while in their second or third decade of life.
* An initial stone attack after age 50 years is relatively uncommon.

Clinical
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, shown below, are often relatively asymptomatic.
o

Complete staghorn calculus that fills the collect...
Complete staghorn calculus that fills the collecting system of the kidney (no intravenous contrast material in this patient). Although many staghorn calculi are struvite (related to infection with urease-splitting bacteria), the density of this stone suggests that it may be metabolic in origin and is likely composed of calcium oxalate. Percutaneous nephrostolithotomy or perhaps even open surgical nephrolithotomy is required to remove this stone.

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Complete staghorn calculus that fills the collect...

Complete staghorn calculus that fills the collecting system of the kidney (no intravenous contrast material in this patient). Although many staghorn calculi are struvite (related to infection with urease-splitting bacteria), the density of this stone suggests that it may be metabolic in origin and is likely composed of calcium oxalate. Percutaneous nephrostolithotomy or perhaps even open surgical nephrolithotomy is required to remove this stone.
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.Differential Diagnoses
Abdominal Abscess
Lumbar Spondylosis
Aortic Dissection
Nephrolithiasis: Acute Renal Colic
Appendicitis
Pancreatitis, Acute
Biliary Colic
Pyonephrosis
Cholecystitis
Renal Arteriovenous Malformation
Constipation
Renal Vein Thrombosis
Diverticulitis
Splenic Abscess
Duodenal Ulcers
Splenic Infarct
Gastritis, Acute
Thoracic Aortic Aneurysm
Gastroenteritis, Viral
Urinary Tract Infection, Females
Glomerulonephritis, Acute
Urinary Tract Infection, Males
Ileus
Urinary Tract Obstruction
Inflammatory Bowel Disease

Liver Abscess

Lumbar Disc Disease

Workup
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 from www.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.3,4,5,6,7,8,9,10 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.11
+ 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 (ESWL; see 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.12 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.13
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.
#

Two calculi in a dependent calyx of the kidney (l...
Two calculi in a dependent calyx of the kidney (lower pole) visualized through a flexible fiberoptic ureteroscope. In another location, these calculi might have been treated with extracorporeal shockwave lithotripsy (ESWL), but, after being counseled regarding the lower success rate of ESWL for stones in a dependent location, the patient elected ureteroscopy. Note that the image provided by fiberoptics, although still acceptable, is inferior to that provided by the rod-lens optics of the rigid ureteroscope in the previous picture.

[ CLOSE WINDOW ]

Two calculi in a dependent calyx of the kidney (l...

Two calculi in a dependent calyx of the kidney (lower pole) visualized through a flexible fiberoptic ureteroscope. In another location, these calculi might have been treated with extracorporeal shockwave lithotripsy (ESWL), but, after being counseled regarding the lower success rate of ESWL for stones in a dependent location, the patient elected ureteroscopy. Note that the image provided by fiberoptics, although still acceptable, is inferior to that provided by the rod-lens optics of the rigid ureteroscope in the previous picture.
+ 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

Please see Cystinuria, Hypercalciuria, Hyperoxaluria, Hyperuricosuria and Gouty Diathesis, Hypocitraturia, and struvite topics for specific information regarding medical therapy for stone disease.

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.

* Dosing
* Interactions
* Contraindications
* Precautions

Adult

2-5 mg IV q15min (limited by RR <16 bpm and systolic BP <100 mm Hg) prn for pain relief Pediatric Not established * Dosing * Interactions * Contraindications * Precautions Phenothiazines may antagonize analgesic effects; tricyclic antidepressants, MAOIs, altered mental status, and CNS depressants may potentiate adverse effects when experienced or used concurrently * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity; hypotension; potentially compromised airway in which rapid establishment of airway control would be uncertain * Dosing * Interactions * Contraindications * Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus 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. * Dosing * Interactions * Contraindications * Precautions Adult 1-2 tab or cap PO q4-6h prn Pediatric Not established * Dosing * Interactions * Contraindications * Precautions Phenothiazines may antagonize analgesic effects of opiates; tricyclic antidepressants, MAOIs, altered mental status, and CNS depressants may potentiate adverse effects of morphine when experienced or used concurrently * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity * Dosing * Interactions * Contraindications * Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus 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. * Dosing * Interactions * Contraindications * Precautions Adult 1-2 tab or cap PO q4-6h prn Pediatric Not established * Dosing * Interactions * Contraindications * Precautions Phenothiazines may antagonize analgesic effects of opiates; tricyclic antidepressants, MAOIs, altered mental status, and CNS depressants may potentiate adverse effects of morphine when experienced or used concurrently * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity * Dosing * Interactions * Contraindications * Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus 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. * Dosing * Interactions * Contraindications * Precautions 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 * Dosing * Interactions * Contraindications * Precautions Coadministration with aspirin increases the risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; phenytoin levels may be increased when administered concurrently * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity; do not administer into CNS or to patients diagnosed with peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, and those at high risk of bleeding * Dosing * Interactions * Contraindications * Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus 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. * Dosing * Interactions * Contraindications * Precautions 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 * Dosing * Interactions * Contraindications * Precautions Synergistic effects with anticoagulants or pentoxifylline imparts risk for GI bleeding; may reduce natriuretic effect of diuretics (attributed to inhibition of renal prostaglandin synthesis); coadministration with probenecid significantly increases ketorolac plasma levels; increases plasma lithium levels; may decrease methotrexate elimination; concomitant use of ACE inhibitors and/or angiotensin II receptor blockers (ARBs) may increase risk of renal impairment, particularly in volume-depleted patients; reports suggest that NSAIDs may diminish ACE inhibitor or ARB antihypertensive effect; coadministration with SSRIs may increase risk for GI bleeding * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity to ketorolac, other NSAIDs, aspirin, or ethylenediamine tetra-acetic acid (EDTA); active peptic ulcer disease, recent GI bleeding or perforation, or history of peptic ulcer disease or GI bleeding; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; prophylactic analgesic before any major surgery; during perioperative period in setting of coronary artery bypass graft (CABG) surgery; advanced renal disease or patients at risk for renal failure due to volume depletion; labor and delivery; breastfeeding women; suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or those for whom hemostasis is critical; coadministration with probenecid or pentoxifylline * Dosing * Interactions * Contraindications * Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus Precautions Black Box Warning Limitations of use: Total duration of use of intranasal formulation, alone or sequentially with other ketorolac formulations, should not exceed 5 d Cardiovascular risk: NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal; risk may increase with duration of use; patients with risk factors for or existing cardiovascular disease may be at greater risk; contraindicated for perioperative pain in setting of CABG surgery (increased risk of MI and stroke) Gastrointestinal risk: NSAIDs increase risk of serious adverse GI events, including bleeding, ulceration, and perforation of stomach or intestines, which can be fatal; adverse GI events may occur at any time during use and without warning symptoms; elderly patients are at greater risk for serious GI events Bleeding risk: Inhibits platelet function and is contraindicated with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or high risk of bleeding Renal risk: Contraindicated with advanced renal impairment and patients at risk for renal failure due to volume depletion 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. * Dosing * Interactions * Contraindications * Precautions Adult 600-800 mg PO q8h Pediatric Not established * Dosing * Interactions * Contraindications * Precautions Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity; do not administer into CNS or to patients diagnosed with peptic ulcer disease, recent GI bleeding or perforation, or renal insufficiency, or to those at high risk of bleeding * Dosing * Interactions * Contraindications * Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus 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. * Dosing * Interactions * Contraindications * Precautions Adult 10 mg PO bid Pediatric Not established * Dosing * Interactions * Contraindications * Precautions Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective-tissue infections; fungal or tubercular skin infections; GI disease * Dosing * Interactions * Contraindications * Precautions Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals 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. * Dosing * Interactions * Contraindications * Precautions Adult 30 mg/d PO extended-release cap Pediatric Not established * Dosing * Interactions * Contraindications * Precautions Caution with coadministration of any agent that can lower BP, including beta-blockers and opioids; H2 blockers (cimetidine) may increase toxicity * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity * Dosing * Interactions * Contraindications * Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus 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. * Dosing * Interactions * Contraindications * Precautions Adult 0.4 mg tab PO qd Pediatric Not established * Dosing * Interactions * Contraindications * Precautions Cimetidine may significantly increase plasma concentrations; tamsulosin may increase toxicity of warfarin * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity * Dosing * Interactions * Contraindications * Precautions Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals 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. * Dosing * Interactions * Contraindications * Precautions Adult 4 mg PO qd, although, in some patients, an increasing dose (2, 4, 8 mg) may be considered Pediatric Not established * Dosing * Interactions * Contraindications * Precautions Effects decrease with coadministration of NSAIDs; effects increase with coadministration of diuretics and antihypertensive medications * Dosing * Interactions * Contraindications * Precautions Documented hypersensitivity * Dosing * Interactions * Contraindications * Precautions Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals 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. * Dosing * Interactions * Contraindications * Precautions 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

* Dosing
* Interactions
* Contraindications
* Precautions

Alcohol decreases effects; incidence of skin rash increases when used concurrently with ampicillin and amoxicillin; large amounts of vitamin C acidify urine and may cause kidney stone formation; inhibits metabolism of azathioprine and mercaptopurine

* Dosing
* Interactions
* Contraindications
* Precautions

Documented hypersensitivity

* Dosing
* Interactions
* Contraindications
* Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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.

* Dosing
* Interactions
* Contraindications
* Precautions

Adult

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

10-40 mEq/d PO divided tid/qid with foodFollow-up
Further Outpatient Care

* Postsurgical issues
o Following surgical treatment of urinary tract calculi, the major issues include infection, ureteral obstruction, and hemorrhage.
o The postoperative course of minimally invasive stone-removal modalities is generally characterized by short-lived discomfort easily managed with oral medications.
+ Continued or severe pain should prompt evaluation for complications.
+ Repeat urine cultures and imaging studies should be performed to assess for ureteral obstruction and perforation, and the degree of circulating blood volume should be evaluated for ongoing hemorrhage.
* Postsurgical follow-up care
o A follow-up examination, including abdominal radiography, is often adequate after an uncomplicated stone-removal procedure.
o Further imaging is often unnecessary in a patient with a previous radiopaque stone who has no further symptoms.
o In the following cases, imaging that includes assessment of renal drainage (eg, IVU, ultrasonography, CT scanning) is usually indicated:
+ Stones with unusual characteristics
+ Difficult or complicated procedures
+ Patients with unusual symptoms
o Once postoperative complications have been excluded and the patient is clinically healthy, standard radiographic follow-up care includes abdominal radiography every 6-12 months. Radiography is often performed in conjunction with metabolic chemoprophylaxis.
* Ongoing medical therapy
o If a patient older than 40 years has formed a single stone that passed spontaneously or was easily treated, follow-up care for recurrent stones may be unnecessary. This patient is at a reasonably low risk for recurrence if adequate fluid intake is maintained.
o In other patients, whether or not they have elected directed metabolic therapy, routine follow-up care consists of plain abdominal radiography (or renal ultrasonography in the case of radiolucent stones) every 6-12 months.
o If medical therapy is instituted, a 24-hour urinalysis 3 months after starting any new therapy should be performed to assess the degree of patient compliance and the adequacy of the metabolic response. Checking all possible metabolic parameters—not just the previously abnormal ones—is necessary because of the possibility of new problems arising as a result of the new therapy.
o Once a stable regimen has been established, annual 24-hour urinalyses are adequate.

Complications

* Serious complications of urinary tract stone disease include the following:
o Abscess formation
o Serious infection of the kidney that diminishes renal function
o Urinary fistula formation
o Ureteral scarring and stenosis
o Ureteral perforation
o Extravasation
o Urosepsis
o Renal loss due to long-standing obstruction

Prognosis

* Because the minimally invasive modalities for stone removal are generally successful in removing calculi, the primary consideration in managing stones is not whether the stone can be removed but whether it can be removed in an uncomplicated manner with minimum morbidity.
* The usually quoted recurrence rate for urinary calculi is 50% within 5 years and 70% or higher within 10 years, although a large, prospective study published in 1999 suggested that the recurrence rate may be somewhat lower at 25-30% over a 7.5-year period. Metabolic evaluation and treatment are indicated for patients at greater risk for recurrence, including those who present with multiple stones, who have a personal or family history of previous stone formation, who present with stones at a younger age, or who have residual stones after treatment.
* Medical therapy is generally effective at delaying (but perhaps not completely stopping) the tendency for stone formation. The most important aspect of medical therapy is maintaining a high fluid intake and subsequent high urinary volume. Without an adequate urinary volume, no amount of medical or dietary therapy is likely to be successful in preventing stone formation.
o According to estimates, merely increasing fluid intake and regularly visiting a physician who advises increased fluids and dietary moderation can cut the stone recurrence rate by 60%. This phenomenon is known as the "stone clinic" effect.
o In contrast, optimal use of metabolic testing with proper evaluation and compliance with therapy can completely eliminate new stones in many patients and significantly reduces new stone formation in most patients.

Patient Education

* A patient who tends to develop stones should be counseled to seek immediate medical attention if he or she experiences flank or abdominal pain or notes visible blood in the urine.
* Numerous internet sites offer kidney stone information, including the National Institutes of Health (NIH) and the American Urological Association Foundation.
* An excellent source of detailed patient information is The Kidney Stones Handbook by Gail Savitz and Stephen W. Leslie. It is available at a reasonable cost directly from the publisher, Grant Gibbs of Four Geez Press, at 530-889-1727 (alternatively, an email can be sent to GSavitz@earthlink.net for ordering information). The Kidney Stones Handbook has received numerous awards and is the only book recommended by the National Institutes of Health (NIH) for patients with kidney stones.
* For other excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Kidney Stones, Blood in the Urine, and Intravenous Pyelogram.

Miscellaneous
Medicolegal Pitfalls

* Failure to offer stone-prevention advice could be a source of medicolegal liability. Numerous patients have claimed they have not been told about stone-prevention options. One anecdotal example from the practice of one of the editors is that of a 65-year-old man with a 5-year history of more than 60 stones. Although he underwent two open surgeries for stone removal, his stones were not evaluated for chemical composition. Eventually, the stones were analyzed and found to be pure uric acid. Although his uric acid excretion rate was normal, he had highly acidic urine, which led to the uric acid calculi formation. After starting oral therapy of allopurinol and potassium citrate, he remained free of stones for 10 years.
* Even patients who develop single stones may be strongly motivated to follow a program for maximum kidney stone prophylaxis. Discussing the pros and cons of a comprehensive stone-prevention program with all patients who have documented kidney stone disease—not with just those who are obviously at high risk—may be prudent.