• Clinical science

Nephrolithiasis (Urolithiasis)

Summary

Nephrolithiasis encompasses the formation of all types of urinary calculi in the kidney, which may deposit along the entire urogenital tract from the renal pelvis to the urethra. Risk factors include low fluid intake, high-sodium, high-purine, and low-potassium diets, which can raise the calcium, uric acid, and oxalate levels in the urine and thereby promote stone formation. Urinary stones are most commonly composed of calcium oxalate. Less common stones are made up of uric acid, struvite (due to infection with urease-producing bacteria), calcium phosphate, or cystine. Nephrolithiasis manifests as sudden onset colicky flank pain that may radiate to the groin, testes, or labia (renal/ureteric colic) and is usually associated with hematuria. Diagnostics include noncontrast spiral CT of the abdomen and pelvis or ultrasound to detect the stone, as well as urinalysis to assess for concomitant urinary tract infection and serum BUN/creatinine to evaluate kidney function. Small uncomplicated stones without concurrent infection or severe dilation of the urinary tract may be managed conservatively with hydration and analgesics to promote spontaneous stone passage. When the spontaneous passage appears unlikely or fails due to the stone's size or location, first-line urological interventions include shock wave lithotripsy, ureterorenoscopy, and, in case of large kidney stones, percutaneous nephrolithotomy. The most important preventive measure is adequate hydration. Collected stones should be sent for chemical analysis because in many cases specific lifestyle guidance, diet changes, and/or initiation of medical treatment (e.g, thiazide diuretics, urine alkalinization) can prevent future stone formation.

Epidemiology

  • Sex: >
  • Peak incidence: 30–60 years
  • Lifetime prevalence: ∼ 9%
  • Risk factors
    • Low fluid intake, dehydration
    • Personal or family history
    • See “Classification” below.

References:[1][2][3][4]

Epidemiological data refers to the US, unless otherwise specified.

Classification

Overview of urinary calculi

Types Incidence Etiology Characteristics Prophylaxis
Crystal appearance Radiopacity Urine alkalinization Urine acidification

Calcium oxalate stones

75%
  • Hypercalciuria
  • Hyperoxaluria
  • Hypocitraturia
  • urine pH

Biconcave dumbbells (calcium oxalate monohydrate) or bipyramidal envelopes (calcium oxalate dihydrate)

✓✓ -
Uric acid stones ∼ 10%

Rounded rhomboids or needle-shaped

- -
Struvite stones ∼ 5–10%
  • UTI with urease-producing bacteria

Rectangular prisms (coffin lid-appearance)

-
Calcium phosphate stones < 5% Wedge-shaped prisms ✓✓ -
Cystine stones

Hexagon-shaped crystals

-
Xanthine stones
  • Xanthinuria
Amorphous crystals - - -

Calcium oxalate stones

  • Types
    • Calcium oxalate monohydrate (“whewellite”): brown or black calculi
    • Calcium oxalate dihydrate (“weddellite”): light yellow calculi
  • Etiology
  • Specific preventive measures
    • Dietary modification
      • Reduced intake of salt and animal protein
      • Reduced intake of oxalate-rich foods and supplemental vitamin C
    • Thiazide diuretics for recurrent calcium-containing stones with idiopathic hypercalciuria (i.e., no hypercalcemia)
    • Urine alkalinization

Crohn disease leads to increased oxalate absorption via malabsorption of fatty acids, which can ultimately cause nephrolithiasis.

Uric acid stones

  • Etiology
  • Specific treatment: oral chemolitholysis via urine alkalinization
  • Specific preventive measures

Uricosuric agents (e.g., probenecid) increase the excretion of uric acid, which can accelerate the formation of stones!

Struvite stones (triple phosphate stones/magnesium ammonium phosphate stones)

Urinary tract infections can cause the formation of struvite stones, but struvite stones also increase the risk of urinary tract infections. It is important to break this vicious cycle!

Less common stones

References:[5][2][6][4]

Clinical features

Stones usually form in the collecting ducts of the kidneys but may be deposited along the entire urogenital tract from the renal pelvis to the urethra. Their localization and size determine the specific symptoms. Small kidney stones may also be asymptomatic and detected incidentally.

  • Severe unilateral and colicky flank pain (renal colic)
    • Radiates anteriorly to the lower abdomen, groin, labia, testicles, or perineum
    • Paroxysmal or progressively worsening
    • The area around the kidneys may be tender on percussion (costovertebral angle tenderness)
  • Hematuria
  • Nausea, vomiting, and reduced bowel sounds
  • Dysuria, frequency, and urgency
  • Passage of gravel or a stone

Depending on the location of the stone, nephrolithiasis may resemble conditions such as appendicitis or testicular torsion!

References:[1][7]

Diagnostics

Initial diagnostic workup includes imaging studies to locate the stone and laboratory tests to determine kidney function and assess for UTI.

  • Laboratory tests
  • Imaging
    • Nonenhanced abdominopelvic CT scan: (gold standard) Demonstrates calculus size, site, density , and degree of obstruction
      • Hydronephrosis: dilatation of the urinary tract proximal to the site of obstruction
      • May be performed using a low-dose or ultra low-dose nonenhanced CT protocol to minimize radiation exposure with comparable sensitivity and specificity
      • Ureteral dilation without stone may indicate recent spontaneous passage
      • Post IV contrast: used to demonstrate the functioning renal parenchyma, may demonstrate indinavir stones
    • Ultrasound: method of choice for patients in whom radiation exposure should be minimized (e.g., pregnant patients, children, recurrent stone formers) or if a gynecological or abdominal differential diagnosis is likely
    • Kidney, ureter, and bladder (KUB) X-ray
    • Intravenous pyelogram (IVP)

Noncontrast abdominopelvic CT scan or ultrasound are the tests of choice for diagnosis of nephrolithiasis!

References:[8][7][9][10]

Differential diagnoses

References:[11]

The differential diagnoses listed here are not exhaustive.

Treatment

Approach considerations

  • Determine if it is a complicated case, including: high-grade or infected hydronephrosis, urosepsis, acute kidney injury, intractable pain, or vomiting
  • Hemodynamically stable patients with uncomplicated stones ≤ 10 mm → a trial of observation with symptomatic treatment to enable spontaneous passage
  • Urological intervention required for:
    • Patients with stones > 10 mm
    • Complicated stones
    • Paitents who decline conservative treatment
    • Failure to pass the stone spontaneously after 4–6 weeks
  • For most patients with kidney or ureteral stones ≤ 20 mm, first-line interventional treatments include both ureterorenoscopy and shock wave lithotripsy.
  • For patient with kidney stones > 20 mm, percutaneous nephrolithotomy is preferred.

Medical therapy

Urological intervention

  • Indications
    • Stones > 10 mm
    • Complicated stones, i.e., concomitant high-grade obstruction, urosepsis, impending acute kidney injury, intractable pain vomiting
    • After failed medical therapy, relapse, recurrent infection, or if preferred by patient
  • Procedures
    • Ureteral stenting or percutaneous nephrostomy : Surgical decompression in case of severely obstructed or infected pyelon; in those cases, definite stone treatment should be delayed until the infection has resolved.
    • Extracorporeal shock wave lithotripsy (SWL)
      • First-line treatment option for renal stones ≤ 20 mm and ureteral stones
      • Lowest complication rate but often repeated SWL is necessary for patients with residual stone burden
      • Stones have to be clearly visible on x-ray and/or ultrasound
      • Contraindicated in case of untreated UTI, during pregnancy, and in patients with bleeding diathesis; not preferred in morbidly obese patients
    • Ureterorenoscopy (URS) ;:
      • First-line treatment option for renal stones ≤ 20 mm and ureteral stones
      • Greatest stone-free rate
      • For stones in the proximal ureter, flexible URS is usually preferred, whereas for distal stones, rigid or semirigid URS is often superior
    • Percutaneous nephrolithotomy : first-line treatment for renal stones > 20 mm
    • Laparoscopic or open stone removal (pyelolithotomy or ureterolithotomy): only considered in rare cases where other interventional methods have previously failed or are likely to do so (e.g., because of complex staghorn stones)

Follow-up imaging is indicated after both conservative and operative treatment to ensure freedom of stones!

References:[8][7][12][13][14][15][16]

Complications

References:[7]

We list the most important complications. The selection is not exhaustive.

Prognosis

  • Stone size and location determines likelihood of spontaneous passage: Stones ≤ 0.5 cm tend to pass spontaneously, while stones ≥ 1 cm are unlikely to do so, especially if located in the pyelon or proximal ureter.
  • 50% of patients may have a new episode of nephrolithiasis within 10 years.

References:[2][3]

Prevention

  • Sufficient fluid intake (≥ 2.5 L/day)
  • For calcium stones:
    • Reduced consumption of salt and animal protein
    • Reduced consumption of oxalate-rich foods and supplemental vitamin C: for oxalate stones
    • Thiazide diuretics for recurrent calcium-containing stones with idiopathic hypercalciuria (i.e., no hypercalcemia)
  • For uric acid stones or high urinary uric acid levels in those with calcium stones: allopurinol
  • Depending on urinary pH and stone composition: urine alkalinization or acidification (see specific measures in the classification section)

Low calcium diets increase the risk of calcium-containing stone formation because they increase oxalate reabsorption!
References:[1][2][4][17][18][19][20]