Urolithiasis

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. 

See main articles: ureteric calculi and bladder stones for further discussion of these.

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, like urinary tract infection as more common) 8.

Urolithiasis can also occur in children and infants, with an even sex distribution, or slight female predilection 24,25.

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 approximately 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. In children, vague abdominal pain is more typical than the classic colicky pain described by adults 26.

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:

horseshoe kidney

duplex collecting system

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 sodium intake

primary hyperparathyroidism

hypervitaminosis D

Cushing syndrome

sarcoidosis

milk-alkali syndrome

hyperoxaluria

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

hypocitraturia

usually idiopathic

renal tubular acidosis (type 1)

chronic diarrhea 

hyperuricosuria

idiopathic/familial

gout

myeloproliferative disorders

high dietary protein intake

urinary tract diversions

ileal conduit

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. 

Rarely the underlying cause is primary oxaluria, a liver enzyme deficiency leading to massive cortical and medullary nephrocalcinosis, and renal failure.

Certain medications 14 can predispose to calcium oxalate or calcium phosphate calculi, including:

loop diuretics

acetazolamide

topiramate

zonisamide

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 stones which are poorly radiopaque

guaifenesin/ephedrine stones which are radiolucent

pure/protein matrix stones

mostly (~65%) made of organic proteins, carbohydrates, and glucosamines (cf. 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 

cystine stones 22

radiopaque compared to soft tissue, although less than calcium-containing calculi, this is not due to calcium as even "pure cystine" stones are radiopaque 22

Lucent stones include:

uric acid

medication (indinavir is best known) 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 the 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 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 (see case 23)

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

phleboliths

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

Randall plaques