• 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 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

Epidemiological data refers to the US, unless otherwise specified.

Classification

Overview of kidney stones

Types Incidence Etiology/associated findings Urine pH
Crystal appearance Radiopacity Prophylaxis

Calcium oxalate stones

  • 75%
  • Biconcave dumbbells or bipyramidal envelopes
Uric acid stones
  • ∼ 10%
  • Urine pH (acidic) and volume (often seen in desert climates)
  • Rounded rhomboids, rosettes, or needle-shaped
Struvite stones
  • ∼ 5–10%
  • Rectangular prisms (coffin lid-appearance)

Calcium phosphate stones

  • < 5%
  • Wedge-shaped prisms
Cystine stones
  • Hexagon-shaped
Xanthine stones
  • Xanthinuria (hereditary)
  • Generally independent of urine pH
  • Amorphous
  • N/A

Types of urinary calculi

Calcium oxalate stones [2]

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

Uric acid stones

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

Uric acid stones are radiolUcent (x-ray negative).

Struvite stones (magnesium ammonium phosphate stones)

Urinary tract infections can lead to the formation of struvite stones, but struvite stones also increase the risk of urinary tract infections.

Calcium phosphate stones [2]

Cystine stones [8]

To remember that cystine crystals are hexagonal, think “The Cystine Chapel has six sides.”

Xanthine stones

2,8-Dihydroxyandenine stones

Ammonium urate stones

Drug-induced stones

Can be caused by:

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. [10]

  • Severe unilateral and colicky flank pain (renal colic) [11]
  • Hematuria
  • Nausea, vomiting, and reduced bowel sounds
  • Dysuria, frequency, and urgency
  • Passage of gravel or a stone
  • Patients are usually unable to sit still and move around frequently (opposed to patients with peritonitis, who usually prefer to lie still)

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

Diagnostics

Initial diagnostic workup includes imaging studies to locate the stone and laboratory tests to determine kidney function and assess for UTI. [13][10]

Laboratory tests

Imaging

  • Abdominopelvic CT [14]
    • Nonenhanced CT scan is the gold standard.
    • May be performed using a low-dose or ultra low-dose nonenhanced CT protocol to minimize radiation exposure with comparable sensitivity and specificity
    • Post IV contrast: used to demonstrate the functioning renal parenchyma, may demonstrate indinavir stones
    • Shows calculus size, site, density , and degree of obstruction
    • Can show hydronephrosis
    • Ureteral dilation without stone may indicate recent spontaneous passage
  • 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
    • May detect nephrolithiasis and hydronephrosis
    • May also detect radiolucent stones (thus useful in combination with x-ray) but small kidney stones are often missed
  • Kidney, ureter, and bladder (KUB) x-ray
    • Usually only suitable for larger stones
    • USeful for follow-up after initiation of treatment
  • Intravenous pyelogram (IVP): rarely used

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

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

Approach considerations [13]

Medical therapy [15]

Noninvasive and surgical interventions [19]

  • Indications
    • Stones > 10 mm
    • Complicated stones (e.g., concomitant high-grade obstruction, urosepsis, impending acute kidney injury, intractable pain, vomiting)
    • After failed medical therapy, relapse, recurrent infection, or if preferred by the patient (i.e., patients who decline conservative treatment)
    • Failure to pass stone spontaneously after 4–6 weeks
  • Procedures
    • Extracorporeal shock wave lithotripsy (SWL): a noninvasive method enabling stone fragmentation using an acoustic pulse.
      • Treatment option for renal and proximal ureteral stones > 10 mm [20][21]
      • Lowest complication rate but often repeated SWL is necessary for patients with residual stones
      • Stones should be clearly visible on x-ray and/or ultrasound
      • Contraindicated in cases of untreated UTI, during pregnancy, and in patients with bleeding diathesis
      • Not preferred in morbidly obese patients
    • Ureterorenoscopy (URS): a transurethral endoscopic procedure used to visualize the urinary tract up to the renal pelvis for retrieval or destruction of urinary stones or sampling of biopsies
      • Treatment option for ureteral stones >10 mm (especially mid or distal ureteral stones) and very large renal stones ≥ 20 mm [20][21]
      • 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: a (minimally-invase) surgical procedure to retrieve kidney stones.
      • Involves the puncture of the renal pelvis calyx under sonographic and radiological guidance → introduction of the nephroscope and instruments → fragmentation of stones and retrieval of the fragments.
      • Treatment option for renal stones > 20 mm [22]
    • Ureteral stenting or percutaneous nephrostomy
      • Stenting can be performed following endoscopic stone removal and in the case of ureteral injury, evidence of ureteral stricture, or large residual stones.
      • Nephrostomy can be used for decompression in the case of severely obstructed or infected pyelon (in these patients, definite stone treatment should be delayed until the infection has resolved).
    • Pyelolithotomy/ureterolithotomy
      • Laparoscopic or open stone removal
      • 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 the absence of stones.

Complications

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

Prognosis

  • Stone size and location determine the likelihood of spontaneous passage: Stones ≤ 5 mm tend to pass spontaneously, while stones ≥ 10 mm are unlikely to do so, especially if located in the pyelon or proximal ureter. [7]
  • 50% of patients may have a new episode of nephrolithiasis within 10 years. [1]

Prevention

  • Hydration: sufficient fluid intake (≥ 2.5 L/day) [17]
  • Diet
    • For calcium stones:
      • Reduced consumption of salt and animal protein [17]
      • Reduced consumption of oxalate-rich foods and supplemental vitamin C: for oxalate stones [23][24]
      • Calcium intake should not be restricted (restriction increases risk of hyperoxaluria, and thereby, the risk for osteoporosis)
    • For uric acid stones: low in purine
    • For cystine stones: low in sodium

Low calcium diets increase the risk of calcium-containing stone formation because they increase oxalate reabsorption.