The main goal of initial treatment for an acute stone event is symptomatic relief with hydration and analgesia/anti-emetics as needed. If signs and symptoms of infection are present, and the patient has a stone in the kidney or ureter, immediate urological consultation should be initiated as urinary tract infection in the setting of an obstructing stone is an emergency that requires antibiotics and renal decompression to decrease the chance of life-threatening septic shock.[44] If the patient has a stone present without signs or symptoms of infection, he or she can be managed conservatively with a non-steroidal anti-inflammatory drug (NSAID) and/or an opioid. NSAIDS have been shown to offer effective pain relief from acute kidney stone related pain with fewer side effects than opioids and paracetamol.[45] If the pain cannot be managed with conservative therapy, then renal decompression or definitive stone treatment should be considered.[1] There is evidence to support that medical expulsive therapy (MET), namely alpha-blockers, may increase ureteral stone passage rate and decrease the time to stone passage, particularly in distal ureteral stones <10 mm in size.[46] [ Cochrane Clinical Answers logo ] However, if a 4- to 6-week trial of MET has been attempted without successful stone passage, the patient should undergo definitive surgical management.

For patients at risk for or with a history of recurrent stones, secondary preventative measures should be tailored towards underlying metabolic factors that promote stone formation. For all such patients, dietary modification with adequate hydration is an essential aspect of on-going management.

Urgent consideration: obstruction and infection

Patients with urinary calculi along with fever and other signs or symptoms of infection need emergency urological consultation for drainage and intravenous antibiotics. Failure to perform rapid renal decompression can perpetuate urosepsis and result in death. Drainage can be accomplished in two ways. A urologist can place a ureteric stent past the obstruction and achieve drainage. Alternatively, a percutaneous nephrostomy tube can be placed by interventional radiology.

Management of stones <10 mm and no complications

Acute medical treatment for renal or ureteric colic includes conservative therapy such as hydration, analgesia (an NSAID and/or an opioid), and an anti-emetic.[45][47] [ Cochrane Clinical Answers logo ] NSAIDs should be offered first-line unless contraindicated (e.g., patients at risk of renal impairment, cardiac failure, gastric ulceration).[38][48][49][Evidence C] Parental NSAIDs provide the most sustained pain relief, with fewer adverse effects, when compared with opioids.[45][50] However, NSAIDs can be offered by any route.[48][Evidence C]

Patients with newly diagnosed ureteric stones <10 mm without complicating factors (urosepsis, intractable pain and/or vomiting, impending acute renal failure, obstruction of a solitary or transplanted kidney, or bilateral obstruction) can be managed expectantly.[51] Many ureteric stones <10 mm pass spontaneously, with exact passage rate related to both stone size and location.[52]

MET using an alpha-blocker such as tamsulosin, alfuzosin, or silodosin may be of benefit in promoting larger (but still <10 mm) distal ureteral stone passage; however, efficacy rates have been questioned.[53][54][55][56][57][58][59] [ Cochrane Clinical Answers logo ]  These agents can cause ureteric relaxation of smooth muscle and antispasmodic activity of the ureter leading to stone passage.[60] Patients should be made aware that prescribing alpha-blockers for this indication is considered an off-label use of these drugs. Additionally, tamsulosin has been associated with intraoperative floppy iris syndrome, therefore it should not be prescribed if a patient has planned cataract surgery.

If there is spontaneous passage of stones, most pass within 4 to 6 weeks. Surgical intervention is indicated in the presence of persistent obstruction, failure of stone progression, sepsis, or persistent or increasing colic. Such patients in general are followed up with periodic imaging, with either a KUB and renal ultrasound or a non-contrast computed tomography (CT) abdomen and pelvis to monitor stone position and degree of hydronephrosis.

Management of stones ≥10 mm or smaller stones that fail to pass with MET

Management can be affected by stone size, location, and composition, in addition to anatomical and clinical features. For larger stones (≥10 mm), and for smaller stones that remain despite conservative therapies, additional surgical treatment is necessary. Historically, open surgery was the only way to remove stones. However, with the development and success of endourology, a term used to describe less invasive surgical techniques that involve closed manipulation of the urinary tract with scopes, open surgery is now rarely performed.

Calculi between 10-20 mm are in general treated with extracorporeal shock wave lithotripsy (ESWL) or ureteroscopy as first-line therapy. However for ESWL, the stone-free rates for lower pole stones are inferior (25%) compared with non-lower pole stones (40%).[61] Percutaneous nephrostolithotomy (PCNL) for calculi between 10-20 mm achieves better stone-free rates for lower pole stones than ESWL.[62] Similarly, cystine stones >15-20 mm and brushite stones respond poorly to ESWL.[63] Hence, patients with features predictive of poor outcome, obesity, or a body build not conducive to ESWL, may be advised alternatives such as PCNL or ureteroscopy, which show superior results.[64] Patients with stones >20 mm should primarily be treated with PCNL unless specific indications for an alternate procedure are present. While PCNL is the first-line therapy for large stones, ureteroscopy has been reported to achieve a mean stone-free rate as high as 93.7% (77.0% to 96.7%) for stones >20 mm in size (mean 25 mm) with acceptable overall complication rates (10.1%). However, this requires an average of 1.6 procedures per patient.[65][66]

For solitary renal calculi <10 mm, ESWL and ureteroscopy are both valid options. Ureteroscopy or PCNL can be utilised when ESWL fails or in the presence of anatomical abnormalities or other special circumstances.[67] A ureteral stent, an internal tube extending from the kidney to the bladder, is often left temporarily in place after ureteroscopy to promote collecting system drainage while any oedema from the stone or the procedure resolves. Stents are recommended in cases of functionally or anatomically solitary kidneys, ureteral stricture, noted ureteral injury, or cases with a planned second stage procedure. While stents can be omitted in cases of uncomplicated ureteroscopy, randomised multicentre trials are warranted to better determine which patients can safely undergo ureteroscopy without ureteral stent placement.[68]

  • Extracorporeal shock wave lithotripsy (ESWL) is the least invasive method of definitive stone treatment and is suitable for most patients with uncomplicated stone disease. In ESWL, shock waves are generated by a source external to the patient's body and are then propagated into the body and focused on a renal stone. The shock waves break stones by both compressive and tensile forces. The stone fragments then pass out in the urine. Limitations to ESWL include stone size and location. ESWL has the potential benefit of being done under intravenous sedation/analgesia, without need for general anaesthesia. Treatment with tamsulosin appears to be effective in assisting stone clearance in patients with renal and ureteric calculi.[69] While ESWL has been shown to have limited success with lower pole stones there is evidence to suggest that ancillary manoeuvres such as percussion, diuresis, and inversion increase stone-free rates.[70] Contraindications to ESWL treatment include pregnancy, severe skeletal malformations, severe obesity, aortic and/or renal artery aneurysms, uncontrolled hypertension, disorders of blood coagulation, and uncontrolled urinary tract infections.[71][72]

  • Ureteroscopy involves placing a small semi-rigid or flexible scope per urethra and into the ureter and/or kidney. Once the stone is visualised, it can be fragmented using a laser and/or grasped with a basket and removed. The procedure is more invasive than ESWL, but is generally thought to have a higher stone-free rate. General anaesthesia is routinely used, and a ureteric stent may be placed at the end of the procedure.[73] [ Cochrane Clinical Answers logo ] The procedure can be safely performed in coagulopathic patients using a holmium laser. Single-use flexible ureteropyeloscopy (FURS) demonstrates comparable efficacy with reusable FURS in treating renal calculi.[74]

  • For patients requiring stone removal, both ESWL and ureteroscopy are considered acceptable first-line surgical treatments for stones in the ureter.[51][38] Ureteroscopic stone-free rates are better than ESWL rates for distal ureteric stones regardless of size and for proximal ureteric stones >10 mm.[75][76] However, ureteroscopic removal has a higher complication rate and longer hospital stay.[77][78]

  • Percutaneous antegrade ureteroscopy involves percutaneous antegrade removal of ureteric stones, and can be considered in select cases with very large (>15 mm) stones impacted in the upper ureter or when retrograde access is not possible.[79][80][81]

  • Percutaneous nephrostolithotomy (PCNL) is a minimally invasive form of treatment that is usually reserved for renal and proximal ureteric stones (i.e., in the lower pole) and those that are large (>20 mm), have failed therapy with ESWL and ureteroscopy, or are associated with complex renal anatomy.[51] Percutaneous access into the kidney is gained from the flank. Current evidence indicates that both fluoroscopy and ultrasound (US) guidance may be successfully used for obtaining percutaneous renal access. Combining US and fluoroscopy seems to improve the outcome both with regard to success in achieving access and reducing complications.[82] Once access is gained, a large sheath is placed into the kidney and a nephroscope is used to help remove the stone. For large stones, ultrasound lithotripsy is usually used to break and remove the stone. PCNL usually requires a hospital stay and has more potential complications than either ESWL or ureteroscopy. In stones of 20-30 mm, ESWL is associated with poor stone-free rates (34%) compared to those achieved with PCNL (90%). ESWL is further associated with an increased number of procedures and need for ancillary treatments as the stone size increases.[83]

  • Laparoscopic stone removal is another minimally invasive method to remove ureteric or renal stones. However, it is still more invasive, requires a longer hospital stay, and has a much higher learning curve than ureteroscopy or ESWL. With the advances in ESWL and endourological surgery (i.e., ureteroscopy and PCNL) during the past 20 years, the indications for open stone surgery have markedly diminished. Laparoscopic or open surgical stone removal may still be indicated in rare cases where ESWL, ureteroscopy, and percutaneous ureteroscopy fail or are unlikely to be successful; anatomical deformities preclude a minimally invasive approach; the patient requires concomitant open surgery, pyeloplasty, or a partial nephrectomy; or in patients with a large stone burden requiring a single clearance procedure.[51][38]

Stones during pregnancy

A symptomatic stone occurs in 1 out of every 200 to 1500 pregnancies with 80% to 90% of these occurring in the second or third trimester.[84] It has been reported that 48% to 80% of stones pass spontaneously during pregnancy.[31][85]

Pregnant women with renal colic that is not controlled with oral analgesia or with an obstructing stone and signs of infection (fever or urinalysis/urine culture showing a possible urine infection) should receive a ureteric stent or percutaneous nephrostomy tube. Of note, these tubes should be changed more often (every 6 to 8 weeks) due to concern for rapid encrustation as a result of the metabolic changes seen with pregnancy. If the patient has no evidence of infection, definitive therapy with ureteroscopy may be performed and has been demonstrated to be safe.[86] ESWL and PCNL are contraindicated in pregnancy.

Ongoing medical therapy and dietary modification

Oral alkalinisation therapy with medications such as potassium citrate and sodium bicarbonate may be beneficial in dissolving uric acid stones and preventing uric acid supersaturation. It may be used for treating uric acid stones that do not require urgent surgical treatment, as well as asymptomatic stones. The ideal goal for alkalinisation therapy for uric acid stones is to maintain the urine pH between 6.5 and 7.0. Potassium citrate is the first-line therapy. In patients with CHF or renal failure, extra care should be taken when prescribing alkalinisation therapy. Alkalinisation therapy also plays an important role in preventing calcium and cystine stones.

Long-term dietary modification is essential for preventing future calculi. This modification is centred on increasing fluid intake. At least 2 litres of urine output daily should be recommended to help prevent future episodes of stone formation.[87]

Decreased dietary sodium, protein, and oxalate should be recommended for stone prevention. Increased citrus fruit intake is recommended to prevent stone recurrence.[88] Normal calcium intake (i.e., 1000 mg/day to 1200 mg/day) is recommended.[88] Dietary calcium restriction can lead to less binding of calcium to oxalate in the GI tract, promoting hyperoxaluria and potentiating the risk for stone formation; furthermore, it could have detrimental effects on bone health.

Where specific metabolic abnormalities exist and are not responsive to dietary modification, specific preventative therapies may be required.[89][90] These include:

  • Uric acid stones: urinary alkalinisation with potassium citrate or sodium bicarbonate

  • Hyperuricosuria, recurrent calcium oxalate stones, and normal urine calcium: allopurinol or febuxostat

    • The US Food and Drug Administration recommends that febuxostat should only be prescribed for patients who can not tolerate allopurinol or where treatment with allopurinol has failed, and who have been counseled regarding cardiovascular risk.[91]

    • The double-blind Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES) safety trial found that cardiovascular death and all cause mortality were significantly more common among patients taking febuxostat than allopurinol (4.3% vs 3.2%, HR 1.34 [95% CI 1.03 to 1.73]; 7.8% vs 6.4%, HR 1.22 [95% CI 1.01 to 1.47], respectively).[92] Treatment group did not differ with respect to a primary composite outcome of cardiovascular events.

    • Febuxostat should be avoided in patients with pre-existing major cardiovascular disease (e.g., myocardial infarction, unstable angina, stroke), unless no other therapy options are appropriate.[93]

  • Hypercalciuria and recurrent calcium stones: thiazide diuretic with or without potassium supplementation (potassium citrate or potassium chloride)

  • Hypocitraturia and recurrent calcium stones: urinary alkalinisation (e.g., potassium citrate; sodium bicarbonate or sodium citrate can be considered if the patient is at risk for hyperkalaemia)[94]

  • Hyperoxaluria: oxalate chelator (e.g., calcium, magnesium, or cholestyramine), potassium citrate, pyridoxine

  • Cystinuria: urinary alkalinisation with potassium citrate, thiol binding agent (e.g., tiopronin which is tolerated better than d-penicillamine)

  • Struvite stones: urease inhibitor (e.g., acetohydroxamic acid), which is best reserved for complex/recurrent struvite stones in which surgical management has been exhausted.[14] Secondary care supervision should be employed as it can produce severe adverse effects such as phlebitis and hypercoagulability.

Most of these strategies are applied to children with nephrolithiasis, although there is a limited number of well-designed trials in this age group.[95][96]

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