- Clinical science
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.
|Types||Incidence||Etiology/associated findings||Urine pH|
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|Uric acid stones|| || |
|Struvite stones|| || || |
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|Cystine stones|| || || |
|Xanthine stones|| || || |
Types of urinary calculi
- Calcium oxalate monohydrate (whewellite): brown or black calculi
- Calcium oxalate dihydrate (weddellite): light yellow calculi
- Hypercalciuria: presence of elevated calcium levels in the urine
Hyperoxaluria: presence of elevated oxalate levels in the urine
- Increased intake of dietary oxalate
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
- Pyridoxine deficiency 
- Hypocitraturia: decreased level of citrate in the urine
- Hyperuricosuria: increased urinary excretion of uric acid
- Develop in persistently acidic urine
- Dietary modification
- Thiazide diuretics for recurrent calcium-containing stones with idiopathic hypercalciuria (i.e., no hypercalcemia)
- (e.g., with potassium citrate)
- Possibly citrate supplementation
Uric acid stones are radiolUcent (x-ray negative).
- Upper UTI with such as Proteus mirabilis, Klebsiella, Staphylococcus saprophyticus, and/or Pseudomonas
- Use of indwelling catheter increases risk
- Develop in persistently alcalic urine
- Carbonate apatite
- Thiazide diuretics
- Diet low in sodium
- (carbon apatite stones)
Cystine stones 
- Clinical features: recurrent kidney stones (manifesting with e.g., flank pain) starting in childhood
To remember that cystine crystals are hexagonal, think “The Cystine Chapel has six sides.”
- Etiology: xanthinuria
- Treatment: reduced dietary intake of purines
- Etiology: increased urinary 2,8-dihydroxyadenine concentration due to hereditary deficiency of adenine phosphoribosyltransferase
- Treatment: allopurinol OR febuxostat
- Etiology: urinary tract infection, malabsorption, hypokalemia
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:
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) 
- 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)
- Urine dipstick and urinalysis
- Urine microscopy: to detect crystals (see “Overview” above)
- Urine culture: obtain in patients with clinical or laboratory signs of UTI
- 24-hour urine profile
- Serum studies
- Metabolic evaluation
Abdominopelvic CT 
- 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
- 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
- Intravenous pyelogram (IVP): rarely used
Approach considerations 
- 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
- See “Prevention” below for general measures.
Medical therapy 
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 
- Analgesia (NSAIDs, IV morphine)
- Medical expulsive therapy: alpha-blockers (e.g., tamsulosin) or calcium-channel blockers (e.g., nifedipine)
- Antibiotics: indicated in case of concomitant UTI
- Antispasmodics (e.g., butylscopolamine) may be considered under certain conditions
- Management of specific stones
Change urinary pH: depends on stone composition
- Urine alkalinization: a treatment regimen to raise urinary pH to 6.5–7.5
- Urine acidification: a treatment regimen to lower the urinary pH to ≤ 7
Noninvasive and surgical interventions 
- 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
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 
- 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.
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).
- 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.
- Hydration: sufficient fluid intake (≥ 2.5 L/day) 
- For calcium stones:
- 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.