Nephrolithiasis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Key Recommendations

The main goal of initial treatment for an acute stone event is symptomatic relief with hydration and analgesia/antiemetics as needed. If signs and symptoms of infection are present, and the patient has a stone in the kidney or ureter, immediate urologic 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.[48][74][75]

Management can be affected by stone size, location, and composition, in addition to anatomic and clinical features.

Urgent consideration: obstruction and infection

Patients with urinary calculi with obstruction, along with fever and other signs or symptoms of infection need emergency urologic consult for drainage and intravenous antibiotics (chosen with consideration of local resistance patterns and suspected pathogen spectrum).[76] Failure to perform rapid renal decompression can perpetuate urosepsis and result in death. Note that this may require urgent transfer to a hospital with inpatient urologic cover (if this is not available). Drainage can be accomplished in one of 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.

Initial management: confirmed stone, not obstructed, no evidence of infection

Acute medical treatment for renal or ureteric colic, without signs and symptoms of infection, includes conservative therapy, such as hydration, analgesia (a nonsteroidal anti-inflammatory drug [NSAID] and/or an opioid), and an antiemetic.[77][78] [ ] NSAIDs should be offered first-line unless contraindicated (e.g., patients at risk of renal impairment, cardiac failure, and gastric ulceration).[48][79][80][Evidence C] NSAIDs have been shown to offer effective pain relief from acute kidney stone related pain with fewer adverse effects than opioids and acetaminophen.[77] Parenteral NSAIDs provide the most sustained pain relief, with fewer adverse effects, when compared with opioids.[77][81] However, NSAIDs can be offered by any route.[79][Evidence C] Acetaminophen and intravenous lidocaine are alternative opioid-sparing options for patients with renal colic, although NSAIDs should remain first-line therapy unless contraindicated.[48][82][83][84] Intravenous lidocaine requires continuous cardiac monitoring, and its use is contraindicated in various cardiac conditions. Consult your local drug information source for a full list of contraindications and cautions before using lidocaine. If the pain cannot be managed with conservative therapy, then renal decompression or definitive stone treatment should be considered.[1]

See sections below for further information on definitive management of stones based on size ("Management based on stone size: <10 mm and no complications" and "Management based on stone size: ≥10 mm or smaller stones that fail to pass with MET").

For patients at risk for, or with a history of recurrent stones, secondary preventive measures should be tailored toward underlying metabolic factors that promote stone formation. For all such patients, dietary modification with adequate hydration is an essential aspect of ongoing management.[46]

Initial management: confirmed stone, not obstructed, evidence of infection

If the patient is symptomatic with confirmed bacteriuria, but there is no obstruction or signs of sepsis, the patient can be treated with conservative therapy, such as hydration, analgesia (an NSAID and/or an opioid), and an antiemetic. and antibiotics.[77][78] Empiric antibiotic therapy should be started pending sensitivity results based on urinalysis cultures.[48] The empiric regimen depends on various factors, including the type of infection, patient factors, and local antibiotic resistance patterns; consult local guidelines for more information on choice of antibiotics.

Once the infection has been treated and has resolved, the stone can be treated based on site and size.[48] See sections below for further information on definitive management of stones based on size ("Management based on stone size: <10 mm and no complications" and "Management based on stone size: ≥10 mm or smaller stones that fail to pass with MET").

If the patient has confirmed bacteriuria but is asymptomatic, it may be more appropriate to treat the stone based on site and size before treating the infection; seek specialist advice. See sections below for further information on definitive management of stones based on size ("Management based on stone size: <10 mm and no complications" and "Management based on stone size: ≥10 mm or smaller stones that fail to pass with MET").

Management based on stone size: <10 mm and no complications

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.[74][85] Patients with urinary calculi with obstruction (in the absence of infection) can be counseled regarding hydration and analgesia; urologic consult is needed, but the timing of this depends on the size of the stone, likelihood of passing it spontaneously, and local availability of urology specialists. Many ureteric stones <10 mm pass spontaneously, with exact passage rate related to both stone size and location.[86] 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.[87] [ ] However, if a 4-6 week trial of MET has been attempted without successful stone passage, the patient should undergo definitive surgical management.

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.[88][89][90][91][92][93][94][95] [ ] These agents can cause ureteric relaxation of smooth muscle and antispasmodic activity of the ureter leading to stone passage.[96] Patients should be made aware that prescribing alpha-blockers for this indication is considered an off-label use of these drugs. Alpha-blockers may cause orthostatic hypotension and syncope; additionally, tamsulosin has been associated with intraoperative floppy iris syndrome, therefore it should not be prescribed if a patient has planned cataract surgery.[97]

If there is spontaneous passage of stones, most pass within 4-6 weeks. In general, such patients are followed-up with periodic imaging, either ultrasound (KUB and renal) or noncontrast computed tomography (abdomen and pelvis), to monitor stone position and degree of hydronephrosis. Surgical intervention is indicated in the presence of persistent obstruction, failure of stone progression, sepsis, or persistent or increasing colic. For solitary renal calculi <10 mm, extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy (URS) are both valid options. URS or percutaneous nephrolithotomy (PCNL) can be utilized when ESWL fails, or in the presence of anatomic abnormalities or other special circumstances.[98]

Management based on stone size: ≥10 mm or smaller stones that fail to pass with MET

Patients with urinary calculi with obstruction (in the absence of infection) can be counseled regarding hydration and analgesia; urologic consult is needed, but the timing of this depends on the size of the stone, likelihood of passing it spontaneously, and local availability of urology specialists.

If the stone is unlikely to pass spontaneously, or the pain cannot be managed with a NSAID (if renal function normal) and/or an opioid, and/or the patient has presented on multiple occasions with symptoms, inpatient admission for pain control should be considered with a urology review for consideration of decompression. Decompression can be accomplished in one of two ways: a urologist can place a ureteric stent past the obstructing stone and achieve renal drainage; alternatively, percutaneous nephrostomy by an interventional radiologist may be performed.

For larger stones (≥10 mm), and for smaller stones that remain despite conservative therapies, where immediate decompression is not indicated, 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. Options include ESWL, PCNL, URS and laparoscopic stone removal. Each of the surgical options has specific indications and considerations, but in general they are all relatively comparable in terms of safety and efficacy.[99]

Calculi between 10 and 20mm are typically treated with ESWL or URS as first-line therapy. However for ESWL, the stone-free rates for lower pole stones are inferior (25%) compared with nonlower pole stones (40%).[100] PCNL and URS for calculi between 10-20 mm achieve better stone-free rates and require fewer auxiliary procedures than ESWL for lower pole stones sized 10-20 mm.[101][102] Similarly, cystine stones >15-20 mm and brushite stones respond poorly to ESWL.[103] 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 URS, which show superior results.[104]

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, URS 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%).[105][106] However, achieving equivalent stone-free rate with URS requires a greater number of total procedures on average compared with PCNL.[105][107]

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 edema 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, randomized multicenter trials are warranted to better determine which patients can safely undergo ureteroscopy without ureteral stent placement.[108]

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 anesthesia. Adjunctive treatment with an alpha-blocker or a diuretic appears to be effective in assisting stone clearance in patients with renal and ureteric calculi.[95][109][110] While ESWL has been shown to have limited success with lower pole stones there is evidence to suggest that ancillary maneuvers such as percussion, diuresis, and inversion increase stone-free rates.[111][112] Contraindications to ESWL treatment include pregnancy, aortic and/or renal artery aneurysms, uncontrolled hypertension, disorders of blood coagulation, and uncontrolled urinary tract infections.[113]
Ureteroscopy involves placing a small semi-rigid or flexible scope per urethra and into the ureter and/or kidney. Once the stone is visualized, 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 anesthesia is routinely used, and a ureteric stent may be placed at the end of the procedure. [ ] 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.[114] The stone-free rate achieved with FURS may be enhanced by preoperative stenting of the ureter, which may also reduce complications such as ureteric injury.[115][116][117]
For patients requiring stone removal, both ESWL and ureteroscopy are considered acceptable first-line surgical treatments for stones in the ureter.[74] Ureteroscopic stone-free rates are better than ESWL rates for distal ureteric stones regardless of size and for proximal ureteric stones >10 mm.[48][118][119] However, ureteroscopic removal has a higher complication rate and longer hospital stay.[120][121]
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.[122][123][124]
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 or ureteral anatomy.[74] 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.[125] Combining US and fluoroscopy seems to improve the outcome both with regard to success in achieving access and reducing complications.[126] 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, ultrasonic and/or ballistic 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 with 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.[127]
Mini-PCNL, which uses a smaller scope and sheath than standard PCNL, results in higher stone-free rate for stones 10-20 mm than URS, but incurs greater blood loss and longer length of hospital stay because mini-PNCL is more invasive than URS.[128][129] Mini-PCNL may be an option for stones <20 mm, as some evidence suggests equivalent stone-free rate with fewer bleeding complications (due to smaller tract size).[130][131][132] However, for an equivalent stone-free rate, mini-PCNL usually requires longer operating time, due to the smaller size of operating equipment.[132]
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 endourologic 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; anatomic 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.[48][74]

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.[133] It has been reported that 48% to 80% of stones pass spontaneously during pregnancy.[134] Patients with stone disease during pregnancy are at risk of adverse maternal and neonatal outcomes, such as gestational diabetes, preterm birth, C-section delivery, and preeclampsia.[135]

The principles of treatment for the acute stone episode are similar in pregnant and nonpregnant patients. However, analgesics, antibiotics, antiemetics, and intravenous fluids are given relative to their safety and risk for that particular trimester. For example, NSAIDs should be avoided, particularly during the first and third trimesters. Alpha-blockers are not recommended as there are no adequate and well-controlled studies in pregnant women. Similarly antibiotics are given according to their risk benefit ratio. Lidocaine is not recommended in pregnancy.

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 6-8 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 and laser lithotripsy may be performed and has been demonstrated to be safe.[136] ESWL and PCNL are contraindicated in pregnancy.

Ongoing medical therapy and dietary modification

Oral alkalinization 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 alkalinization 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 alkalinization therapy due to high sodium and potassium loads with the medication. Alkalinization therapy also plays an important role in preventing calcium and cystine stones.

Long-term dietary modification is essential for preventing future calculi.[46] This modification is centered on increasing fluid intake. In patients that are known stone formers, a target urine output of 2 to 2.5 L per day is recommended; intake volume may need to be up to 4 L per day to achieve this.[17][18][19]

Decreased dietary sodium, animal protein intake, and oxalate should be recommended for stone prevention.[47] Increased citrus fruit intake is recommended to prevent stone recurrence. Normal calcium intake (i.e., 1000 mg/day to 1200 mg/day) is recommended. 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 preventive therapies may be required.[17][137] These include:

Uric acid stones: urinary alkalinization with potassium citrate or sodium bicarbonate.
Hyperuricosuria, recurrent calcium oxalate stones, and normal urine calcium: allopurinol or febuxostat.
- 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.[138]
- 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).[139] Treatment group did not differ with respect to a primary composite outcome of cardiovascular events.
- Febuxostat should be avoided in patients with preexisting major cardiovascular disease (e.g., myocardial infarction, unstable angina, stroke), unless no other therapy options are appropriate.[140]
Hypercalciuria and recurrent calcium stones: thiazide diuretic with or without potassium supplementation (e.g., potassium citrate)
Hypocitraturia and recurrent calcium stones: urinary alkalinization (e.g., potassium citrate; sodium bicarbonate can be considered if the patient is at risk for hyperkalemia)[141]
Hyperoxaluria: oxalate chelator (e.g., calcium, magnesium, or cholestyramine), potassium citrate, pyridoxine
Cystinuria: urinary alkalinization with potassium citrate, thiol binding agent (e.g., tiopronin which is tolerated better than penicillamine)[2]
Struvite stones: vigilant monitoring and treatment for urinary tract infections with or without long term antibiotic prophylaxis.[17] Urease inhibitors (e.g., acetohydroxamic acid) are best reserved for complex/recurrent struvite stones, in which surgical management has been exhausted.[31] 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.[142][143]

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