Urolithiasis refers to the presence of calculi anywhere along the course of the urinary tracts. For the purpose of the article, the terms urolithiasis, nephrolithiasis and renal/kidney stones are used interchangeably, although some authors have slightly varying definitions of each.
Most patients tend to present between 30-60 years of age 1.
The lifetime incidence of renal stones is high, seen in as many as 5% of women and 12% of males. By far the most common stone is calcium oxalate, however, the exact distribution of stones depends on the population and associated metabolic abnormalities (e.g. struvite stones are more frequently encountered in women, as urinary tract infection as more common) 8.
Although some renal stones remain asymptomatic, most will result in pain. Small stones that arise in the kidney are more likely to pass into the ureter where they may result in renal colic. Hematuria, although common, may be absent in ~15% of patients 1. Strangury is also occasionally present. Some patients may also present with the complication of obstructive pyelonephritis, and may therefore have a septic clinical presentation.
The composition of urinary tract stones varies widely depending upon metabolic alterations, geography and presence of infection, and their size varies from gravel to staghorn calculi. The more common composition of stones include (more detail below):
- calcium oxalate +/- calcium phosphate: ~75%
- struvite (triple phosphate): 15%
- pure calcium phosphate: 5-7%
- uric acid: 5-8%
- cystine: 1%
- lithogenic medications: 1% 14,18
Certain risk factors have been identified including 8:
- low fluid intake
- urinary tract malformations:
- urinary tract infections
- especially with urease producing bacteria (see below)
- urease hydrolyzes urea to ammonium thus increasing urinary pH
- cystinuria: congenital disorder
- hypercalciuria: most common metabolic abnormality
- high dietary oxalate (vegetarians)
- low gut absorption of calcium, leading to increased absorption of oxalate
- low dietary intake of calcium
- malabsorption / ileal disease (e.g. Crohn disease) resulting in fats binding calcium
- usually idiopathic
- renal tubular acidosis (type 1)
- chronic diarrhea
- urinary tract diversions
Most renal calculi contain calcium, usually in the form of calcium oxalate (CaC2O4) and often mixed with calcium phosphate (CaPO4) 1,6. In most instances, no specific cause can be identified, although most patients have idiopathic hypercalciuria without hypercalcemia.
Brushite is a unique form of calcium phosphate stones that tends to recur quickly if patients are not treated aggressively with stone prevention measures and are resistant to treatment with shock wave lithotripsy.
Interestingly hyperuricosuria is also associated with increased calcium containing stone formation and is thought to be related to the uric acid crystals acting as a nidus on which calcium oxalate and calcium phosphate can precipitate 6.
Certain medications 14 can predispose to calcium oxalate or calcium phosphate calculi, including:
- loop diuretics
Struvite (magnesium ammonium phosphate or "triple phosphate") stones are usually seen in the setting of infection with urease-producing bacteria (e.g. Proteus, Klebsiella, Pseudomonas and Enterobacter), resulting in hydrolysis of urea into ammonium and increase in the urinary pH 6,10. They can grow very large and form a cast of the renal pelvis and calyces resulting in so-called staghorn calculi. The struvite accounts for ~70% of these calculi and is usually mixed with calcium phosphate thus rendering them radiopaque. Uric acid and cystine are also found as minor components.
Hyperuricosuria is not always associated with hyperuricemia and is seen in a variety of settings (see above), although in most instances uric acid stones occur in patients with no identifiable underlying etiology 6. Uric acid crystals form and remain insoluble at acidic urinary pH (below 5).
Cystine stones are also formed in acidic urine and are seen in patients with congenital cystinuria.
medication stones 14,18:
- indinavir stones are typically radiolucent (see case 13)
- indinavir is a protease inhibitor, a class of antiretroviral drugs used in HIV treatment
- the formation of renal tract stones has since been described with other members of the protease inhibitor class
- magnesium trisilicate stones which are poorly radiopaque
- ciprofloxacin stones which are radiolucent
- sulphonamides stones which are radiolucent
- triamterene tones which are poorly radiopaque
- guaifenesin/ephedrine stones which are radiolucent
- indinavir stones are typically radiolucent (see case 13)
- pure/protein matrix stones
- mostly (~65%) made of organic proteins, carbohydrates, and glucosamines (c.f. with other stones which are crystalline with only a minor organic element) 15
These depend on the stone composition and vary according to modality. The much greater sensitivity of CT to tissue attenuation means that some stones radiolucent on plain radiography are nonetheless radiopaque on CT.
Calcium-containing stones are radiopaque:
- calcium oxalate +/- calcium phosphate
- struvite (triple phosphate) - usually opaque but variable
- pure calcium phosphate
Lucent stones include:
- uric acid
- indinavir stones
- pure matrix stones (although may have a radiodense rim or center 15)
Intravenous urography (IVU) is a traditional radiographic study of the renal parenchyma, pelvicalyceal system, ureters and the urinary bladder. It involves administration of intravenous contrast. This exam has been largely replaced by non-contrast CT.
Ultrasound is frequently the first investigation of the urinary tract, and although by no means as sensitive as CT, it is often able to identify calculi. Small stones and those close to the corticomedullary junction can be difficult to reliably identify. Ultrasound compared to CT KUB reference showed a sensitivity of only 24% in identifying calculi. Nearly 75% of calculi not visualized were <3 mm 13. Features include 7:
Pulsed wave (PWD) and color flow doppler (CFD) are further sonographic modalities that may act as a diagnostic aid, and assess for the presence of complications;
ureteric jets in obstructive uropathy tend to be shorter, slower, and occur less often
- suggested cutoff values vary; the combination of fewer than 1.5 jets per minute, with peak velocities below 19.5 cm/s and jet durations less than 2.5 seconds have specificities ranging between 87 and 97% 21
- the renal resistive index (RI) is significantly higher in obstructed kidneys
- contralateral unaffected renal RI comparison useful
- elevation in RI may precede pelvicalyceal dilation 22
On CT almost all stones are opaque but vary considerably in density.
- calcium oxalate +/- calcium phosphate: 400-600 HU
- struvite (triple phosphate): usually opaque but variable
- pure calcium phosphate: 400-600 HU
- uric acid: 100-200 HU
- cystine: opaque
Two radiolucent stones are worth mentioning 11:
- protease inhibitor (indinavir) stones
- radiolucent and usually undetectable on non-contrast CT 5
- characterized on delayed phase as a filling defect in the ureter
- pure matrix stones
Ninety-nine percent of renal tract calculi are visible on a non-contrast CT. Given that one of the commonest sites for a stone to become lodged is the vesicoureteric junction, some centers perform the study in the prone position to establish if the stone is retained within the intravesical component of the ureter or has already passed into the bladder itself.
Dual-energy CT is a technique allowing the composition of the calculus to be determined, by assessing stone attenuation at two different kVp levels. Each CT vendor has its own algorithms for the use of dual-energy CT for assessing stone composition. Dual-energy CT may be useful in detecting stones concealed by the opacification of the collecting system 16.
Dual-energy CT has also been shown to predict the success of extracorporeal shock wave lithotripsy 16.
Treatment and prognosis
Indications for surgical management include:
- larger stones, typically that above 5mm in size
- extended duration of symptoms
- location of stone, with proximal calculi less likely to spontaneously pass
- infection or septic features
- certain professions (airline pilot, truck driver) due to the risk of renal colic during work
- solitary kidney
- failed conservative management
Surgical intervention typically involves a retrograde ureteric stent with subsequent laser lithotripsy. In acutely septic patients who would be unsuitable for an anesthetic or in those who would not be suitable for a retrograde stent, such as those with poor retrograde access or abnormal anatomy, a percutaneous nephrostomy (PCN) with an antegrade stent followed by laser lithotripsy is preferred.
Extracorporeal shock wave lithotripsy (ESWL) is usually performed in large proximal calculi in patient unsuitable for invasive management.
Percutaneous nepholithotomy (PCNL) is usually reserved for large calculi near the pelvo-ureteric junction, especially staghorn calculi, which are unlikely to be removable via retrograde access.
Small asymptomatic stones in the kidney can be safely ignored, and if patients maintain good states of hydration, the risk of recurrent symptoms can be dramatically reduced 10. In all settings, a search for a possible underlying cause of hyperoxaluria/hypercalciuria should be sought and if present corrected when possible.
Larger stones may be treated with:
Struvite stones are usually large (staghorn calculi) and result from infection. These stones need to be treated surgically and the entire stone removed, including small fragments, as otherwise, these residual fragments act as a reservoir for infection and recurrent stone formation.
Uric acid stones
Uric acid stones usually are the result of low urinary pH, and hydration and elevation of urinary pH to approximately 6 are usually sufficient (note rendering the urine too alkali (e.g. >pH 6.5) may result in calcium stone formation) 10.
Cystine stones may be difficult to treat and are difficult to shatter with ESWL. Hydration and alkalinisation are usually first-line therapy.
Recognized complications include:
- spontaneous extravasation: spontaneous rupture of renal pelvis (SRRP) +/- urinoma formation 4
- recurrent urinary tract infections (pyelonephritis)
- impaction of the stone along the ureter may result in hydroureter and/or hydronephrosis
- chronic obstruction may lead to progressive renal parenchymal damage, impaired renal function and renal failure 19
- although rare, urolithiasis is a risk factor for squamous metaplasia and squamous carcinoma (possibly as a result of chronic local inflammation and infection) 20
The differential of renal calculi is essentially that of abdominal calcifications. On CT there is usually little confusion as not only is CT exquisitely sensitive in detecting stones, but their location can also be precisely noted. If non-contrast CT is equivocal for the location of the calcification, then a repeat CT with urographic phase contrast is usually able to clarify
Thus the differential diagnosis is predominantly on plain radiograph, and to a lesser degree ultrasound:
- cholelithiasis overlying right kidney
- pancreatic calcification
- calcified mesenteric lymph nodes
- renal artery calcification 7
- intrarenal gas (only a differential for ultrasound)
- acoustic shadow is usually 'dirtier'
- gas typically more mobile than stones
- pure/protein matrix stones may mimic an upper tract soft tissue mass 15
- 1. Tamm EP, Silverman PM, Shuman WP. Evaluation of the patient with flank pain and possible ureteral calculus. Radiology. 2003;228 (2): 319-29. doi:10.1148/radiol.2282011726 - Pubmed citation
- 2. Heneghan JP, McGuire KA, Leder RA et-al. Helical CT for nephrolithiasis and ureterolithiasis: comparison of conventional and reduced radiation-dose techniques. Radiology. 2003;229 (2): 575-80. doi:10.1148/radiol.2292021261 - Pubmed citation
- 3. LeRoy AJ. Diagnosis and treatment of nephrolithiasis: current perspectives. AJR Am J Roentgenol. 1994;163 (6): 1309-13. AJR Am J Roentgenol (abstract) - Pubmed citation
- 4. Mitty HA. CT for diagnosis and management of urinary extravasation. AJR Am J Roentgenol. 1980;134 (3): 497-501. AJR Am J Roentgenol (abstract) - Pubmed citation
- 5. Saw KC, McAteer JA, Monga AG et-al. Helical CT of urinary calculi: effect of stone composition, stone size, and scan collimation. AJR Am J Roentgenol. 2000;175 (2): 329-32. AJR Am J Roentgenol (full text) - Pubmed citation
- 6. Fishman MC, Hoffman AR. Medicine. Lippincott Williams & Wilkins. (2004) ISBN:0781725437. Read it at Google Books - Find it at Amazon
- 7. Kane RA, Manco LG. Renal arterial calcification simulating nephrolithiasis on sonography. AJR Am J Roentgenol. 1983;140 (1): 101-4. AJR Am J Roentgenol (citation) - Pubmed citation
- 8. Young VB, Kormos WA, Chick DA et-al. Blueprints Medicine. Lippincott Williams & Wilkins. (2009) ISBN:0781788706. Read it at Google Books - Find it at Amazon
- 9. Tchelepi H, Ralls PW. Color comet-tail artifact: clinical applications. AJR Am J Roentgenol. 2009;192 (1): 11-8. doi:10.2214/AJR.07.3893 - Pubmed citation
- 10. Nissenson AR, Berns JS, Lerma E. CURRENT Diagnosis & Treatment Nephrology & Hypertension. McGraw-Hill Professional. (2008) ISBN:0071447873. Read it at Google Books - Find it at Amazon
- 11. Morcos SK, Morcos S, Thomsen H. Urogenital Imaging, A Problem-Oriented Approach. Wiley. (2009) ISBN:0470510897. Read it at Google Books - Find it at Amazon
- 12. Guest AR, Cohan RH, Korobkin M et-al. Assessment of the clinical utility of the rim and comet-tail signs in differentiating ureteral stones from phleboliths. AJR Am J Roentgenol. 2001;177 (6): 1285-91. AJR Am J Roentgenol (full text) - Pubmed citation
- 13.Fowler KA, Locken JA, Duchesne JH et-al. US for detecting renal calculi with nonenhanced CT as a reference standard. Radiology. 2002;222 (1): 109-13. Radiology (full text) - doi:10.1148/radiol.2221010453 - Pubmed citation
- 14. Matlaga BR, Shah OD, Assimos DG. Drug-induced urinary calculi. Rev Urol. 2011;5 (4): 227-31. Free text at pubmed - Pubmed citation
- 15. Wein AJ, Kavoussi LR, Partin AW et-al. Campbell-Walsh Urology. Elsevier. ISBN:B01761AWD0. Read it at Google Books - Find it at Amazon
- 16. Murray N, Darras KE, Walstra FE, Mohammed MF, McLaughlin PD, Nicolaou S. Dual-Energy CT in Evaluation of the Acute Abdomen. (2019) Radiographics : a review publication of the Radiological Society of North America, Inc. 39 (1): 264-286. doi:10.1148/rg.2019180087 - Pubmed
- 17. Yongzhi L, Shi Y, Jia L, Yili L, Xingwang Z, Xue G. Risk factors for urinary tract infection in patients with urolithiasis-primary report of a single center cohort. (2018) BMC urology. 18 (1): 45. doi:10.1186/s12894-018-0359-y - Pubmed
- 18. Daudon M, Jungers P. Drug-induced renal calculi: epidemiology, prevention and management. (2004) Drugs. 64 (3): 245-75. doi:10.2165/00003495-200464030-00003 - Pubmed
- 19. Keddis MT, Rule AD. Nephrolithiasis and loss of kidney function. (2013) Current opinion in nephrology and hypertension. 22 (4): 390-6. doi:10.1097/MNH.0b013e32836214b9 - Pubmed
- 20. Jongyotha K, Sriphrapradang C. Squamous Cell Carcinoma of the Renal Pelvis as a Result of Long-Standing Staghorn Calculi. (2015) Case reports in oncology. 8 (3): 399-404. doi:10.1159/000440764 - Pubmed
- 21. Jandaghi AB, Falahatkar S, Alizadeh A, Kanafi AR, Pourghorban R, Shekarchi B, Zirak AK, Esmaeili S. Assessment of ureterovesical jet dynamics in obstructed ureter by urinary stone with color Doppler and duplex Doppler examinations. (2013) Urolithiasis. 41 (2): 159-63. doi:10.1007/s00240-012-0542-7 - Pubmed
- 22. Jandaghi AB, Falahatkar S, Alizadeh A, Kanafi AR, Pourghorban R, Shekarchi B, Zirak AK, Esmaeili S. Assessment of ureterovesical jet dynamics in obstructed ureter by urinary stone with color Doppler and duplex Doppler examinations. (2013) Urolithiasis. 41 (2): 159-63. doi:10.1007/s00240-012-0542-7 - Pubmed