eMedicine Specialties > Urology > Stones

Nephrolithiasis: Treatment & Medication

Author: J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
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Updated: Sep 28, 2009

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
  • 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
  • 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 approach for 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.^{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.
  • 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
  • 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 alkalization of the urine.
  • 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.
  • 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.
  • 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 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.
  • 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 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
  • 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
  • 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 (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 (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.
  • 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.

Oxycodone and acetaminophen (Percocet)

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

Hydrocodone and acetaminophen (Vicodin)

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

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.

Ibuprofen (Motrin, Advil)

Oral NSAID for outpatient management.

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.

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.

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.

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.

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.

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.

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