INTRODUCTION

Section 2 of 11  

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• Clinical
• Differentials
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• Follow-up
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Background

Nephrolithiasis is a common disease that is estimated to produce medical costs of $2.1 billion per year in the United States. Nephrolithiasis specifically refers to calculi in the kidneys, but this article discusses both renal calculi (Image 1) 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 (Image 3) is likely caused by 2 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.

Other current theories also include renal tubular damage or dysfunction as an important component of the initiation of stone formation. The initial crystal agglomerations likely form in distal collecting tubules that drain into the renal papilla. As these masses grow, they gradually extrude into the collecting system through the papilla and eventually drop off to become free urinary calculi.

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 2 million patients present on an outpatient basis with stone disease each year in the United States, which is a 40% increase from 1994.

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 obstruction and upper urinary tract infection. Pyelonephritis, pyonephrosis, and urosepsis can ensue.

Race

Urinary tract calculi are far more common 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 frequent in whites.

Sex

• In general, urolithiasis is more common in males (male-to-female ratio, 2-3:1).
• 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 patients 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

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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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.
• • Renal colic is characterized by undulating cramps and severe pain and is often associated with nausea and vomiting.
  • As the stone travels through the ureter, the pain moves from the flank to the upper abdomen, then to the lower abdomen, down to the groin, and eventually to the scrotal or labial areas.
  • Associated bladder irritative symptoms are common when the stone is located in the distal or intramural ureter.
• Patients with large renal stones known as staghorn calculi (Image 2) are often relatively asymptomatic.
• • 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.
  • Asymptomatic bilateral obstruction, which is uncommon, manifests as symptoms of renal failure.
• Important historical features are as follows:
• • Duration, characteristics, and location of pain
  • History of urinary calculi
  • Prior complications related to stone manipulation
  • Urinary tract infections
  • Loss of renal function
  • Family history of calculi
  • Solitary or transplanted kidney

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 infrequently correlates 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.
• Hypercalciuria is the most common metabolic abnormality.
• Magnesium and especially citrate are important inhibitors of stone formation in the urinary tract. Decreased levels of these in the urine cause a predisposition for 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 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.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Urinalysis
• • Evaluate the urine for evidence of hematuria and infection. Approximately 85% of patients with urinary calculi exhibit hematuria.
  • 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
• • In the context of nephrolithiasis, an elevated white blood cell count suggests renal or systemic infection.
  • 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
• • These are needed to assess a patient's current renal function and to begin the assessment of metabolic risk for future stone formation.
  • A high serum uric acid level may indicate gouty diathesis or hyperuricosuria, while hypercalcemia suggests either renal-leak hypercalciuria or hyperparathyroidism.
  • If the serum calcium level is elevated, serum PTH levels are usually obtained.
• Twenty-four–hour urine collection for levels of pH, calcium, oxalate, uric acid, sodium, phosphorus, citrate, magnesium, creatinine, and total volume
• • 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.
  • 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
    • 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 frequent and possible symptomatic calculi.
• • 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 dietary calcium restriction, thiazide diuretics, oral calcium binders, or phosphate supplementation.
      • Resorptive hypercalciuria is primary hyperparathyroidism and requires parathyroidectomy.
      • Renal-leak hypercalciuria, which is relatively uncommon, is usually associated with secondary hyperparathyroidism and is best managed with thiazide diuretics.
    • Another clinical approach to hypercalciuria, once hyperparathyroidism has been excluded with appropriate blood tests, is to avoid excessive dietary calcium (usual recommendation, 600-800 mg/d) and to use thiazides. If thiazide therapy fails, additional workup (eg, calcium-loading test, more thorough evaluation) may be needed.
    • 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 levels. The supplement should not contain added vitamin D because this increases calcium absorption, leaving less in the intestinal tract to bind to oxalate.
    • 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.
  • 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 they 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. 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.
  • 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.
    • 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 defined than that of citrate.
  • 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.
  • 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.
  • pH: Some stones, such as those composed of uric acid or cystine, are pH-dependent, meaning that they can form only in acidic or basic conditions. 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 or in identifying occult stone disease in some patients.

Imaging Studies

• Plain abdominal radiography
• • Plain abdominal radiography (also known as a flat plate or kidney, ureter, and bladder [KUB] radiography) may suffice for assessing total stone burden, as well as the size, shape, and location of urinary calculi in some patients.
  • 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.
  • When used with other imaging studies, such as a renal sonography 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 be helpful in planning surgical therapy.)
• Renal ultrasonography
• • Renal sonography by itself is frequently adequate to determine the presence of a renal stone. The study is mainly used 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.
  • 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.
  • Ureteral calculi, especially in the distal ureter, and stones smaller than 5 mm are not easily observed with ultrasonography.
• Intravenous urography
• • An intravenous urography (IVU) test, also known as an intravenous pyelography (IVP), is the standard for determining the size and location of urinary calculi. IVU provides anatomical and functional information.
  • A replacement imaging technique is being sought because IVU is a labor-intensive imaging study.
  • • 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.
  • Although some authorities have advocated substituting plain abdominal radiography plus renal ultrasonography for IVU, a helical CT scan without contrast material is currently believed to be the best radiographic examination for acute renal colic.
  • The so-called delayed nephrogram on the IVU is one of the hallmark signs of acute urinary 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.
  • The IVU is helpful in identifying the specific problematic stone among numerous pelvic calcifications and for establishing that the other kidney is functional. These determinations are particularly helpful if the degree of hydronephrosis is mild and the CT scan findings are not definitive.
• Helical CT scanning without contrast material
• • Technological advances in CT scanning allow imaging of the entire abdomen in a single breath hold.
  • When performed with thin cuts 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.
  • Contrast is not used because it makes the entire urinary collecting system appear white on the study, thus masking the stones.
  • At most institutions that offer this examination, CT scanning has replaced or is replacing IVU for the assessment of urinary tract stone disease, especially for acute renal colic.
  • 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.
  • • Visualization is especially useful if surgery is being considered.
    • It is extremely helpful in observing the patient because only KUB radiography may be needed later to determine if the stone has moved or passed.
    • A lucent stone 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 a renal colic noncontrast CT scan is performed.
  • 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.
  • 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.
    • At most institutions, CT scanning is still more expensive than IVU.
• Plain renal tomography
• • Although largely replaced by helical CT scanning without contrast (when available), 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.
  • Tomography does not require extensive preparation and can be performed quickly.
  • 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.
  • Plain renal tomography is also useful in 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

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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). Additionally, as suggested above, consider aggressive treatment in patients who initially formed stones before age 30 years, as they are more likely to have recurrent stone formation.

• General guidelines for emergency management are as follows:
• • After diagnosing renal (ureteral) colic, determine the presence or absence of obstruction or infection.
  • 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.
  • 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).
  • 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 are as follows:
• • 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.
  • 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.
    • 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 of renal (ureteral) colic.
  • 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.
  • • 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 shock-wave lithotripsy) inasmuch as the stone fragments resulting from treatment appear to clear the system more effectively.
  • 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-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
• • 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.
  • Prophylactic therapy might include limitation of dietary components, addition of stone-formation inhibitors or intestinal calcium binders, and, most importantly, augmentation of fluid intake.
  • 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
• • 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 alkalinization of the urine.
  • Sodium bicarbonate can be used as the alkalinizing agent, but potassium citrate is usually preferred because of the availability of slow-release tablets and the avoidance of a high sodium load.
  • The dosage of the alkalinizing 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.
  • Even very large uric acid calculi can be dissolved in patients who comply with therapy. Roughly 1 cm per month dissolution can be achieved.
  • 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.
  • 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.
  • 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:
• • Active, untreated urinary tract infection
  • Uncorrected bleeding diathesis
  • 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 by either 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.
• • 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.
  • Infection combined with obstruction in the urinary tract 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 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.
• Extracorporeal shock-wave lithotripsy
• • Approximately 85% of urinary tract calculi that require treatment are currently managed with this modality. ESWL is the least invasive of the surgical methods of stone removal. This modality was once felt 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 once believed.
  • The patient, under varying degrees of anesthesia, depending on the type of lithotriptor, 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 shocks (60-80 per minute) and, possibly, double shocking afford better results.
  • The shock head delivers shock waves developed from an electrohydraulic, electromagnetic, or piezoelectric source. The shock waves are focused on the calculus, and the energy released as the shock wave impacts the stone produces fragmentation. The resulting small fragments pass in the urine.
  • SWL 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.
• Ureteroscopy
• • Ureteroscopic manipulation of a stone is the next most commonly applied modality (see Image 4). 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 either be directly extracted using a basket or grasper or be 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.
• 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 SWL 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.

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

• For 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.
• Dietary calcium should not be altered unless specifically indicated by 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 per day 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

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Please see Nephrolithiasis: Laboratory Evaluation of Stone Formers, Nephrolithiasis: Prevention of Kidney Stones, 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.

Drug Category: Opioid analgesics

These agents are used for pain relief.

Drug Name	Oxycodone and acetaminophen (Percocet)
Description	Drug combination indicated for oral relief of moderate to severe pain.
Adult Dose	1-2 tab or cap PO q4-6h prn
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	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
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

Drug Name	Hydrocodone and acetaminophen (Vicodin)
Description	Drug combination indicated for oral relief of moderate to severe pain.
Adult Dose	1-2 tab or cap PO q4-6h prn
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	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
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

Drug Category: 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.

Drug Name	Ibuprofen (Motrin, Advil)
Description	Oral NSAID for outpatient management.
Adult Dose	600-800 mg PO q8h
Pediatric Dose	Not established
Contraindications	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
Interactions	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
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	Category D in third trimester of pregnancy; caution in patients with congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy

Drug Category: Corticosteroids

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

Drug Category: Calcium channel blockers

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

Drug Category: Alpha blockers

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

Drug Name	Terazosin (Hytrin)
Description	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 Dose	4 mg PO qd, although, in some patients, an increasing dose (2, 4, 8 mg) may be considered
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Effects decrease with coadministration of NSAIDs; effects increase with coadministration of diuretics and antihypertensive medications
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

Drug Category: Uricosuric agents

These agents help prevent nephropathy and recurrent calcium oxalate calculi.

Drug Category: Alkalinizing agents, oral

These agents are used for the treatment of metabolic acidosis and when long-term maintenance of alkaline urine is desirable.

Drug Name	Potassium citrate (Urocit K)
Description	Wax matrix tabs that contain 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.
Adult Dose	30-90 mEq/d PO divided tid with food
Pediatric Dose	10-40 mEq/d PO divided tid with food
Contraindications	Documented hypersensitivity; severe renal impairment with oliguria/azotemia; hyperkalemia; untreated Addison disease; acute dehydration
Interactions	Increased drug effect with potassium-containing medications, potassium-sparing diuretics, ACE inhibitors, or cardiac glycosides (could lead to toxicity); drugs that slow GI transit time (ie, anticholinergics) may increase GI side effects
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	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

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

• Postsurgical issues
• • Following surgical treatment of urinary tract calculi, the major issues include infection, ureteral obstruction, and hemorrhage.
  • 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
• • A follow-up examination, including abdominal radiography, is often adequate after an uncomplicated stone removal procedure.
  • Further imaging is often not necessary if a patient with a previous radiopaque stone has no further symptoms.
  • 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
  • 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
• • 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 not be necessary. This patient is at a reasonably low risk for recurrence if adequate fluid intake is maintained.
  • 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.
  • 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.
  • Once a stable regimen has been established, annual 24-hour urinalyses are adequate.

Complications

• Serious complications of urinary tract stone disease include the following:
• • Abscess formation
  • Serious infection of the kidney that diminishes renal function
  • Urinary fistula formation
  • Ureteral scarring and stenosis
  • Ureteral perforation
  • Extravasation
  • Urosepsis
  • 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, those who have a history of previous stone formation, and those who present with stones at a younger age.
• 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 an increased fluid intake and high urinary volume. Without an adequate urinary volume, no amount of medical or dietary therapy is likely to be successful in preventing stone formation.
• • 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.
  • In contrast, optimal use of metabolic testing with proper evaluation and compliance with therapy can completely eliminate new stones in at least 75% of patients and significantly reduces new stone formation in up to 98% of 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 of Internet sites offer kidney stone information, including the National Institutes of Health (NIH) and the American Foundation for Urologic Disease (AFUD).
• 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 from online booksellers such as Amazon.com and directly from the publisher, Four Geez Press, at 1-800-2KIDNEYS. A patient newsletter for patients who form kidney stones is available from the same publisher.
• For 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

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal 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 example is that of a 65-year-old man with a 5-year history of more than 60 stones. Although he underwent 2 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.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Small renal calculus that would likely respond to extracorporeal shock-wave lithotripsy.
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Media type:  X-RAY