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
- Sex: ♂ > ♀ [1]
- Peak incidence: 45–70 years [1]
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Risk factors: See “Classification” below.
- Personal or family history
- Low fluid intake, dehydration
- Loop diuretics
- Postcolectomy and/or postileostomy
Epidemiological data refers to the US, unless otherwise specified.
Classification
Overview of kidney stones
Types | Incidence | Etiology/associated findings | Urine pH | ||||
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Crystal appearance | Radiopacity | Prophylaxis | |||||
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Uric acid stones |
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Struvite stones |
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Cystine stones |
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Xanthine stones |
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Types of urinary calculi
Calcium oxalate stones [2]
-
Types
- Calcium oxalate monohydrate (whewellite): brown or black calculi
- Calcium oxalate dihydrate (weddellite): light yellow calculi
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Etiology
- Hypercalciuria: presence of elevated calcium levels in the urine
-
Hyperoxaluria: presence of elevated oxalate levels in the urine
- Increased intake of dietary oxalate
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Increased intestinal absorption of oxalate, e.g., due to fatty acid malabsorption (e.g., Crohn disease, ulcerative colitis, short bowel syndrome)
- Calcium normally binds oxalate to form calcium oxalate, which is excreted via feces.
- In conditions associated with fatty acid malabsorption due to impaired bile acid reabsorption, calcium preferentially binds free fatty acids, leading to excess free oxalate and, therefore, to increased oxalate absorption.
- Vitamin C supplements
- Ethylene glycol poisoning [3]
- Pyridoxine deficiency [4]
- Hypocitraturia: decreased level of citrate in the urine
- Hyperuricosuria: increased urinary excretion of uric acid
- Develop in persistently acidic urine
-
Diagnosis
- Urine microscopy: dumbbell-shaped or octahedron-shaped crystals
- X-ray (or CT): radiopaque stones
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Treatment [5][6]
- Hydration
- Dietary modification
- Reduced intake of salt (mainly sodium) and animal protein
- Reduced intake of oxalate-rich foods and supplemental vitamin C
- Calcium intake should not be restricted (restriction increases risk of hyperoxaluria, and thereby, the risk for osteoporosis)
- Thiazide diuretics for recurrent calcium-containing stones with idiopathic hypercalciuria (i.e., no hypercalcemia)
- Urine alkalinization (e.g., with potassium citrate)
- Possibly citrate supplementation
Crohn disease leads to increased oxalate absorption via malabsorption of fatty acids, which can ultimately cause nephrolithiasis.
Uric acid stones
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Etiology
-
Hyperuricemia and hyperuricosuria
- Gout
- High cell turnover (e.g., tumor lysis syndrome, myelodysplastic syndrome)
- ↓ Urine volume; , e.g., due to dehydration (often seen in desert climates)
- Develop in persistently acidic urine [7]
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Hyperuricemia and hyperuricosuria
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Diagnosis
- Urine microscopy: rhomboid/needle-shaped crystals
- X-ray: radiolucent stones
- CT: can be visible but are usually only minimally visible (not as visible as calcium stones)
- US and/or intravenous pyelogram may also be helpful in diagnosis
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Treatment
- Hydration
- Oral chemolitholysis via urine alkalinization
- Low-purine diet
- Allopurinol
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)
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Etiology
- Upper UTI with urease-producing bacteria such as Proteus mirabilis, Klebsiella, Staphylococcus saprophyticus, and/or Pseudomonas
- Use of indwelling catheter increases risk
- Develop in persistently alcalic urine
-
Diagnosis
- Urine microscopy: rectangular prisms (coffin lid-appearance) indicate struvite stones
-
X-ray (or CT)
- Weakly radiopaque stones
- Possibly staghorn calculi
-
Treatment
- Antibiotic treatment of urinary tract infections
- Hydration
- Urine acidification
- Usually require surgical stone removal
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]
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Types
- Carbonate apatite
- Brushite
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Etiology
- Hyperparathyroidism (brushite)
- Type 1 renal tubular acidosis (brushite)
- Upper urinary tract infections (carbonate apatite)
- Develop in persistently alcalic urine
-
Diagnosis
- Urine microscopy: wedge-shaped crystals
- X-ray (or CT): radiopaque stones
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Prevention
- Hydration
- Thiazide diuretics
- Diet low in sodium
- Urine acidification (carbon apatite stones)
Cystine stones [8]
-
Etiology
- Autosomal recessive defect in cystine-reabsorbing PCT transporter → impaired proximal renal tubular absorption of dibasic amino acids → cystinuria → cystine stone formation (as cystine is poorly soluble)
- Develop in persistently acidic urine
- Clinical features: recurrent kidney stones (manifesting with e.g., flank pain) starting in childhood
-
Diagnosis
- Urine microscopy: hexagonal crystals
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X-ray (or CT)
- Weakly radiopaque stones
- Possibly staghorn calculi
- Positive cyanide nitroprusside test
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Prevention
- Hydration
- Diet low in sodium
- Urine alkalinization
- Chelating agents (e.g., penicillamine) for refractory cases
- Tiopronin
To remember that cystine crystals are hexagonal, think “The Cystine Chapel has six sides.”
Xanthine stones
-
Etiology: xanthinuria
- Hereditary deficiency of xanthine oxidase → failure to convert xanthine to uric acid
- Allopurinol
-
Diagnosis
- Urine microscopy: amorphous crystals
- Urine pH: plays little role in diagnosis [9]
- X-ray: radiolucent stones (require further evaluation with CT, US, and/or intravenous pyelogram)
- Treatment: reduced dietary intake of purines
2,8-Dihydroxyandenine stones
- Etiology: increased urinary 2,8-dihydroxyadenine concentration due to hereditary deficiency of adenine phosphoribosyltransferase
- Treatment: allopurinol OR febuxostat
Ammonium urate stones
- Etiology: urinary tract infection, malabsorption, hypokalemia
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Treatment
- Antibiotic treatment of UTI as indicated
- Urine acidification
Drug-induced stones
Can be caused by:
- Crystallization of drug compounds in the urine, which is most commonly associated with:
- Stone formation due to alterations in urine composition, which are most commonly associated with:
- Acetazolamide
- Furosemide
- Topiramate
- Vitamin D, vitamin A
- Aluminium magnesium hydroxide
- Calcium
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]
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Severe unilateral and colicky flank pain (renal colic) [11]
- Radiates anteriorly to the lower abdomen, groin, labia, testicles, or perineum
- Paroxysmal or progressively worsening [12]
- 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
- 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. [10][13]
Laboratory tests
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Urine dipstick and urinalysis
- Gross or microscopic hematuria
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Urine pH
- > 7 suggests urea-splitting organisms and struvite stones
- < 5 indicates uric acid stones
- Pyuria, positive leukocyte esterase, positive nitrites, and/or bacteriuria suggest UTI
- Urine microscopy: to detect crystals (see “Overview” above)
- Urine culture: obtain in patients with clinical or laboratory signs of UTI
- 24-hour urine profile
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Serum studies
- ↑ WBC: suggests concomitant UTI
- ↑ Serum urea nitrogen and creatinine: suggests acute kidney injury
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Metabolic evaluation
- Indicated in recurrent stone formers and high-risk, first-time stone formers (e.g., patients with a solitary or transplanted kidney)
- Includes serum calcium, phosphorus, uric acid, bicarbonate, PTH, albumin, and/or alkaline phosphate: to detect metabolic abnormalities (e.g., hyperparathyroidism)
Imaging
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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
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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
- May detect total number, size, composition, and location of stones.
- Not useful for evaluating calcium stones < 3 mm, radiolucent stones, or to identify urinary tract obstruction
- Intravenous pyelogram (IVP): rarely used
Noncontrast abdominopelvic CT scan or ultrasound are the tests of choice for diagnosis of nephrolithiasis.
Differential diagnoses
- Causes of acute abdomen (see “Differential diagnoses of acute abdominal pain”)
- Causes of hydronephrosis (see “Upper urinary tract obstruction”)
- Causes of testicular pain (see “Differential diagnosis of scrotal pain”)
- Urinary tract infection: cystitis or pyelonephritis
The differential diagnoses listed here are not exhaustive.
Treatment
Approach considerations [13]
- Determine if it is a complicated case, including: high-grade or infected hydronephrosis, urosepsis, acute kidney injury, intractable pain, or vomiting
-
Treatment depends on the size of the stone
- < 5 mm: often pass spontaneously
- < 10 mm: likelihood of spontaneous passage increases with alpha-blocker or CCB therapy.
- > 10 mm: often require shock wave lithotripsy or ureterorenoscopy
- > 20 mm: percutaneous nephrolithotomy
- See “Prevention” below for general measures.
Medical therapy [15]
-
Uncomplicated stones: In hemodynamically stable patients with uncomplicated stones ≤ 10 mm begin a trial of observation with symptomatic treatment to enable spontaneous passage.
- Hydration in case of dehydration or planned IVP [16]
- Analgesia (NSAIDs, IV morphine)
-
Medical expulsive therapy: alpha-blockers (e.g., tamsulosin) or calcium-channel blockers (e.g., nifedipine)
- Relieve spasms of ureter muscles
- Promote the passage of ureteral stones < 10 mm
- Reduce the need for analgesics
- Antibiotics: indicated in case of concomitant UTI
- Antispasmodics (e.g., butylscopolamine) may be considered under certain conditions
-
Management of specific stones
-
Calcium stones
- Thiazide diuretic for recurrent calcium-containing stones with idiopathic hypercalciuria (i.e., no hypercalcemia) [17][18]
- Allopurinol in the case of high urine uric acid
- Uric acid stones: allopurinol [17]
- Cystine stones: tiopronin
- Struvite stones: antibiotic treatment for UTI
-
Calcium stones
-
Change urinary pH: depends on stone composition
-
Urine alkalinization: a treatment regimen to raise urinary pH to 6.5–7.5
- Achieved via diet rich in fruits and vegetables or supplementation of potassium citrate
- Used to prevent recurrence of calcium oxalate, uric acid, and cystine stones
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Urine acidification: a treatment regimen to lower the urinary pH to ≤ 7
- Achieved via diet rich in cranberry juice, dairy products, grains, and/or meat or supplementation of citrate (which is converted to HCO3 in the liver)
- Used to prevent recurrence of calcium phosphate and struvite stones
-
Urine alkalinization: a treatment regimen to raise urinary pH to 6.5–7.5
Noninvasive and surgical interventions [19]
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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
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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
-
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)
-
Extracorporeal shock wave lithotripsy (SWL): a noninvasive method enabling stone fragmentation using an acoustic pulse.
Follow-up imaging is indicated after both conservative and operative treatment to ensure the absence of stones.
Complications
- Recurrent urinary tract infections → risk of pyelonephritis, urosepsis, and perinephric abscess
- Urinary obstruction → inflammation of the kidney and hydronephrosis → permanent glomerular damage if left untreated
- Acute kidney injury [10]
We list the most important complications. The selection is not exhaustive.
Prognosis
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
-
For calcium stones:
Low calcium diets increase the risk of calcium-containing stone formation because they increase oxalate reabsorption.