- ACRONYMS AND DEFINITIONS
- AUA - American Urological Assoc
- BMI - Body mass index
- EAU - European Association of Urology
- HCTZ - Hydrochlorothiazide
- MET - Medical expulsive therapy
- PNL - Percutaneous nephrolithotomy
- RCT - Randomized controlled trial
- SWL - Shockwave lithotripsy
- PREVALENCE
- Kidney stones are a worldwide problem affecting all races and geographic regions
- The prevalence of kidney stones in the U.S. has risen over the past several decades from around 3% to 5%
- By the age of seventy, 11% of men and 6% of women will have experienced a symptomatic kidney stone [1,2,4]
- RISK FACTORS
GENERAL RISK FACTORS | |
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Risk factor | Comment |
Previous stone |
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Male sex |
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White race |
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Family history |
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Obesity |
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MEDICAL CONDITIONS | |
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Medical condition | Comment |
Parathyroid disease |
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Gout |
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Shortened bowel syndrome (e.g. bariatric surgery, intestinal resection) |
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Pancreatic insufficiency |
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Sarcoidosis |
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Renal tubular acidosis type 1 |
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Primary hyperoxaluria |
|
Anatomical abnormalities |
|
DIETARY RISK FACTORS | |
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Dietary factor | Comment |
Low fluid intake |
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High/low calcium intake |
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High sodium intake |
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High purine intake |
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High oxalate intake |
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Fruits and vegetables vs meats, cheese, and eggs |
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Vitamin C |
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Vitamin D |
|
MEDICATIONS THAT PROMOTE STONE FORMATION | |
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Medication | Comment |
Acetazolamide (Diamox®) |
|
Allopurinol |
|
Amoxicillin |
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Ceftriaxone (Rocephin®) |
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Ephedrine |
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Fenofibrate |
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Guaifenesin |
|
Indinavir (Crixivan®) |
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Laxatives |
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Lithium |
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Loop diuretics |
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Losartan |
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Mesalamine |
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Orlistat (Xenical®) |
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Probenecid / Lesinurad |
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Quinolones (ciprofloxacin, levofloxacin, etc.) |
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SGLT2 inhibitors |
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Sulindac |
|
Sulpha drugs |
|
Topiramate (Topamax®) |
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Triamterene |
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Zonisamide |
|
Zonisamide (Zonegran®) |
|
- RISK OF RECURRENT STONES
- In patients who have passed a kidney stone, the overall risk of recurrence is 40% at 5 years and 75% at 20 years [1,2,4]
- A cohort study that followed 3364 patients with first symptomatic kidney stone from 1984 to 2017 was used to create a model for predicting kidney stone recurrence. A calculator based on the model is available at this link - Recurrent kidney stone risk predictor
- Factors in the study that were associated with an increased risk of recurrent stone included the following: younger age, male sex, higher BMI, family history of stones, pregnancy, incident asymptomatic stone on imaging before the first episode, suspected stone episode before the first episode, history of a brushite, struvite, or uric acid stone, no history of calcium oxalate monohydrate stone, kidney pelvic or lower pole stone on imaging, no ureterovesical junction stone on imaging, number of kidney stones on imaging, and diameter of the largest kidney stone on imaging.
- Stone recurrence rates seen in the study are detailed in the table below [15]
Annual risk of recurrent kidney stone | |
---|---|
Stones passed | Annual risk of recurrence |
1 | 3.4% |
2 | 7.1% |
3 | 12.1% |
≥ 4 | 17.6% |
- FACTORS ASSOCIATED WITH STONE FORMATION
- Overview
- Kidney stones form when urinary factors promote the crystallization of urinary compounds (most commonly calcium)
- The majority of kidney stones are calcium stones, and they appear to form over calcium plaques (called Randall's plaques) that develop in the renal papilla. See kidney illustration below.
- Once a kidney stone forms, it may remain in the renal calyces or pelvis (typically with no symptoms), or it may pass into the ureter where symptoms can occur depending on the size
- A number of factors play a role in the promotion of crystallization and stone formation
- Hypercalciuria
- Mechanism
- Increased urinary calcium promotes stone formation by increasing the amount of calcium available to bind to oxalate and phosphate [1]
- Causes
- Familial idiopathic hypercalciuria
- Hyperparathyroidism
- Sarcoidosis
- ↑ Vitamin D/Calcium intake
- Loop diuretics
- Normal urinary calcium values
- Men: < 300 mg/day
- Women: < 250 mg/day
- Hyperoxaluria
- Mechanism
- Oxalate is an end product of metabolism in humans, and it is also found in certain foods. Oxalate is eliminated in the kidneys, and when concentrations are high, it can bind calcium and form stones. Calcium oxalate stones are the most common type of kidney stone.
- Dietary oxalate that ends up in the intestine may exist in a free form or bound to calcium. Free oxalate is much more readily absorbed than oxalate bound to calcium. Because of this, conditions that reduce intestinal calcium can promote oxalate absorption and lead to stone formation. Reduced intestinal calcium can occur from decreased consumption, and this is why patients with kidney stones are sometimes told to increase their calcium intake. Unabsorbed fats can also sequester calcium and reduce its ability to bind oxalate; this means that fat malabsorption (e.g. shortened bowel syndrome, bariatric surgery) can also increase oxalate absorption. [1,6]
- Causes
- Low dietary calcium (↑ oxalate absorption)
- Fat malabsorption (bowel surgery, etc.)
- High dietary oxalate intake
- Primary hyperoxaluria
- ↑ Vitamin C (metabolized to oxalate)
- Normal urinary oxalate values
- < 40 mg/day
- Hypocitraturia
- Mechanism
- Citrate is a weak acid that has two roles in preventing stone formation
- Citrate permits base excretion without raising urinary pH. Citrate also forms a soluble complex with calcium and prevents it from forming crystals.
- Low levels of urinary citrate can promote stone formation [2]
- Causes
- Renal tubular acidosis
- Hypokalemia
- Medications (topiramate, acetazolamide)
- Men: > 450 mg/day
- Women: > 550 mg/day
- Hyperuricosuria
- Mechanism
- Uric acid is a byproduct of purine metabolism
- Hyperuricosuria plays a role in the formation of two different types of stones. Uric acid promotes calcium stone formation by decreasing the solubility of calcium oxalate. Uric acid can also crystallize and form its own stones (uric acid stones). [1,2]
- Causes
- Obesity
- Gout
- ↑ Dietary purines
- Normal urinary uric acid values
- Men: < 800 mg/day
- Women: < 750 mg/day
- Urinary pH
- Mechanism
- Alkaline urinary pH (> 6.2) can promote calcium phosphate stone formation through supersaturation
- Alkaline urinary pH also increases urinary citrate concentrations which helps prevent stones
- Acidic urinary pH (< 5.5) promotes uric acid stone formation [1,2]
- Normal urinary pH
- 5.8 - 6.2
- STONE TYPES
Kidney Stone Types |
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Calcium oxalate - 67% of stones
|
Calcium phosphate (apatite) - 16% of stones
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Uric acid - 8% of stones
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Struvite - 3% of stones
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Calcium phosphate (brushite) - 0.9% of stones
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Cystine stones - 0.4% of stones
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Staghorn stones - rare
|
- KIDNEY ILLUSTRATION

- NATURAL COURSE OF KIDNEY STONES
- Renal stones
- Renal stones are stones that are present in the renal pelvis and/or calyces (see kidney illustration)
- Renal stones do not typically cause symptoms and are often discovered incidentally during imaging studies for other indications
- The natural course of renal stones is not well-defined
- A small study followed the natural history of 160 asymptomatic renal stones (average size 7 mm) in 110 patients
- Over an average follow-up of 3.4 years, the following was seen:
- 28% of the stones caused symptoms during follow-up
- 17% of stones required intervention
- 7% of the stones passed spontaneously
- 2% of the stones caused painless silent obstruction necessitating intervention
- Upper pole and mid-renal stones were more likely to become symptomatic and to pass spontaneously than lower pole stones
- 20% of stones grew in diameter by > 50% [8]
- Ureteral stones
- Ureteral stones are stones that have passed from the renal pelvis into the ureter (see kidney illustration)
- Ureteral stones typically cause symptoms, although very small stones may not
- The size of the stone determines whether or not it will pass completely or become stuck and require intervention
- In general, the following is true regarding stone size and spontaneous passage rates:
- For stones up to 4 mm in size, 95% will pass within 40 days
- For stones 5 - 10 mm in size, approximately 61% will pass within 28 days of becoming symptomatic
- Stones ≥ 10 mm generally will not pass
- As stone size increases, the probability of passage decreases [3,10]
- SYMPTOMS
- Overview
- Renal stones are generally asymptomatic, although a small percentage may cause obstructive symptoms leading to flank pain
- Ureteral stones are typically symptomatic
- Classic symptoms of kidney stones include the following:
- Sudden onset of severe, intermittent, colicky flank pain on the side of stone passage. Pain may radiate to the groin.
- Nausea and vomiting
- Pain in the testicle or labia (lower ureteral stones)
- Urinary frequency and oliguria may be present
- Dysuria (once stone reaches bladder) [2,3,11]
- DIAGNOSIS
- Non-contrast-enhanced CT scan
- Preferred imaging study for diagnosing kidney stones
- Able to detect uric acid stones
- Can detect stone density, inner structure of the stone, and skin-to-stone distance (important information for shockwave therapy)
- Low-dose CT scans can be used in patients with BMI < 30
- Sensitivity: 97%
- Specificity: 95%
- Ultrasound
- Does not expose patient to radiation so is preferred in certain situations (e.g. pregnancy)
- Renal stones: Sensitivity: 45% | Specificity: 88%
- Ureteral stones: Sensitivity: 45% | Specificity: 94%
- X-ray (KUB)
- A plain film X-ray of the abdomen will show Radiopaque (seen on X-ray) stones
- Typically used to follow stone progression after diagnosis with a CT scan
- Sensitivity: 44 - 77%
- Specificity: 80 - 87%
- Intravenous pyelogram (IVP)
- An IVP is performed by giving the patient IV contrast and then taking X-rays of the kidneys, ureters, and bladder (KUB)
- The contrast makes the urinary system visible on the X-ray
- IVP used to be the preferred method for detecting kidney stones, but it has largely been replaced by CT scans [3]
- Urinalysis
- All patients with symptoms of kidney stones should have a urinalysis
- Symptomatic ureteral stones typically cause gross or microscopic hematuria. In one study (n=140), 85% of patients presenting to the ER with documented urinary lithiasis had hematuria on urinalysis. When a positive urinalysis or a positive urine dipstick was used as criteria, 94% of patients had hematuria. [13]
- Any urinary signs of infection should be investigated promptly
- Serum electrolytes, calcium level
- All patients should have serum electrolytes and calcium levels checked
- Elevated calcium levels should raise suspicion for hyperparathyroidism
- Reduced serum bicarbonate and elevated chloride should raise suspicion for renal tubular acidosis type 1
- Uric acid, serum
- Uric acid levels should be checked in high-risk patients (e.g. gout, obesity)
- Normal values
- Male: 3.7 - 8.6 mg/dl
- Female: 2.5 - 7.1 mg/dl
- 24-hour urine testing
- Recurrent and high-risk stone formers should have 24-hour urine testing. First-time stone formers may also elect to be tested.
- 24-hour urine should be obtained while consuming a random diet
- The AUA recommends that 24-hour urine testing include the following: urine volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine
- Creatinine is measured to assess compliance with 24-hour collection
- Potassium may be used to assess compliance with medications
- Sodium is measured to assess dietary sodium intake
- Calcium, oxalate, uric acid, citrate, and pH are risk factors for stone formation - see factors in stone formation above
- Normal values
- Urine volume: > 1500 ml/day
- Urine pH: 5.8 - 6.2
- Calcium:
- < 300 mg/day (men)
- < 250 mg/day (women)
- Alternative: < 4 mg/kg/day in either sex
- Oxalate:
- 7 - 44 mg/day (men)
- 4 - 31 mg/day (women)
- Uric acid: 250 - 750 mg/day
- Citrate: 320 - 1240 mg/day
- Sodium: 40 - 220 mmol/day
- Potassium: 25 - 125 mmol/day
- Creatinine:
- 20 - 24 mg/kg/day (men)
- 15 - 19 mg/kg/day (women)
- Stone analysis
- If stone is available, stone analysis should be performed to determine the type of stone
- Parathyroid hormone (PTH)
- Primary hyperparathyroidism should be considered when calcium level is high or high-normal
- Intact PTH (active form) should be drawn
- Normal values
- 15 - 65 pg/ml
- Cystine, 24-hour urine
- In patients where cystine stones are suspected
- Normal values
- 10 - 100 mg/day [1,5,12,14]
- TREATMENT
- Renal stones (stones in the renal pelvis and/or calyces)
- There is no consensus guideline or accepted standard for the treatment of renal stones
- Renal stones are typically asymptomatic, and their natural course has not been well-defined (see natural course above)
- The European Association of Urology recommendations for renal stone management are discussed in the table below
EAU recommendations for renal stone management |
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Observation
|
Shockwave lithotripsy (SWL)
|
Percutaneous nephrolithotomy (PNL)
|
Ureterorenoscopy
|
Urinary alkalinization (uric acid stones)
|
- Ureteral stones
- The management of ureteral stones is largely dictated by stone size
- Smaller stones may pass spontaneously, while larger stones may become stuck in the ureter and require intervention for removal
EAU recommendations for ureteral stone management |
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Observation
|
Medical expulsive therapy (MET)
|
Shockwave lithotripsy (SWL)
|
Ureterorenoscopy
|
- PREVENTION
AUA Stone Prevention Recommendations |
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All stones
|
Calcium stones
|
Uric acid stones
|
Cystine stones
|
Medications to Prevent Kidney Stones |
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Allopurinol
|
Potassium citrate
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Thiazide diuretics
|
- MET STUDIES
- The study enrolled 512 patients presenting to the ER with newly-diagnosed, symptomatic ureteral stones < 9 mm in diameter
Main inclusion criteria
- Symptomatic ureteral stone < 9 mm in diameter confirmed on CT scan
Main exclusion criteria
- Concurrent UTI
- Prior ureter/kidney surgery
Baseline characteristics
- Average age 40 years
- Average stone size - 3.8 mm
- Stone size ≤ 4 mm - 74% of patients
- Stone location: Ureterovesical junction - 44% | Distal ureter - 24% | Proximal ureter 17%
Randomized treatment groups
- Group 1 (267 patients) - Tamsulosin 0.4 mg once daily for 30 days
- Group 2 (245 patients) - Placebo once daily for 30 days
Primary outcome: The primary outcome was passage of a ureteral stone within 28 days after randomization, as
determined by the participant’s visualization or physical capture of the stone
Results
Duration: 28 days | |||
Outcome | Tamsulosin | Placebo | Comparisons |
---|---|---|---|
Primary outcome | 49.6% | 47.3% | p=0.60 |
Stone passed on follow-up CT (N=238) | 83.6% | 77.6% | p=0.24 |
Surgery for stone | 6.5% | 6.9% | p=0.89 |
|
Findings: Tamsulosin did not significantly increase the stone passage rate compared with placebo. Our findings do not support the use of tamsulosin for
symptomatic urinary stones smaller than 9 mm. Guidelines for medical expulsive therapy for urinary stones may need to be revised.
- A study in the Annals of Emergency Medicine enrolled 403 patients with distal ureteral stones who presented to the ER with ureteral colic
Main inclusion criteria
- Distal ureteral stone ≤ 10 mm on CT scan (distal ureter defined as distal to the sacroiliac joint)
Main exclusion criteria
- GFR < 60 ml/min
- Temp > 100.4°F
Baseline characteristics
- Median stone size - 3.8 mm
- Stones 5-10 mm in size - 26%
- Vesicoureteric junction stone - 64%
Randomized treatment groups
- Group 1 (198 patients) - Tamsulosin 0.4 mg once daily for 28 days
- Group 2 (195 patients) - Placebo once daily for 28 days
- A prespecified subgroup analysis comparing stone < 5 mm to stones 5-10 mm was performed. Randomization was stratified by stone size (< 5 mm and 5-10 mm)
Primary outcome: The coprimary outcomes were stone expulsion and time to stone expulsion. Stone expulsion was defined as absence
of stone on repeated, noncontrast, limited pelvic CT at 28 days. Time to stone expulsion in days was defined as self-reported definitive passage of the calculus or first
day of a pain-free 48-hour period, with calculus absent on repeated CT.
Results
Duration: 28 days | |||
Outcome | Tamsulosin | Placebo | Comparisons |
---|---|---|---|
Stone expulsion (overall) | 87% | 82% | diff 5%, 95%CI [-3 to 13] |
Stone expulsion for stones < 5 mm (N=239) | 88% | 89.5% | diff -1.5%, 95%CI [-9.5 to 6.5] |
Stone expulsion for stones 5 - 10 mm (N=77) | 83% | 61% | diff 22%, 95%CI [3.1 to 41.6] |
Median time to stone passage (overall) | 7 days | 11 days | p=0.10 |
|
Findings: We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did increase passage and should be considered.
- A study in the Lancet enrolled 1167 patients with newly diagnosed kidney stones presenting to hospitals with ureteral colic
Main inclusion criteria
- 18 - 65 years of age
- One kidney stone ≤ 10 mm in diameter in either ureter identified on CT scan
Main exclusion criteria
- Sepsis
- GFR < 30 ml/min
- Need for immediate intervention
Baseline characteristics
- Average age 42 years
- Average stone size 4.5 mm
- Stone size: ≤ 5 mm - 75% | > 5 mm - 25%
- Location: Upper ureter 24% | Middle ureter 11% | Lower ureter 65%
Randomized treatment groups
- Group 1 (391 patients) - Tamsulosin 0.4 mg once daily for 28 days
- Group 2 (387 patients) - Nifedipine 30 mg once daily for 28 days
- Group 3 (389 patients) - Placebo once daily for 28 days
Primary outcome: Spontaneous stone passage in 4 weeks (defined as the absence of need for additional interventions to assist
stone passage at 4 weeks after randomisation)
Results
Duration: 4 weeks | ||||
Outcome | Tamsulosin | Nifedipine | Placebo | Comparisons |
---|---|---|---|---|
Primary outcome | 81% | 80% | 80% | p>0.05 |
Average number of days to stone passage | 16.5 | 16.2 | 15.9 | p>0.05 |
|
Findings: Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic
- Summary
- The three studies above found no conclusive benefit of tamsulosin or nifedipine in facilitating kidney stone passage. In subgroup analyses, a possible benefit from tamsulosin for upper ureteral stones and stones 5 - 10 mm in size could not be ruled out.
- BIBLIOGRAPHY
- 1 - PMID 20818905 - NEJM review
- 2 - PMID 16443041 - Lancet review
- 3 - EAU Guidelines on Urolithiasis 2015
- 4 - PMID 25364887 - ACP treatment recs
- 5 - PMID 24857648 - AUA 2014 treatment GL
- 6 - PMID 23944302 - Hyperoxaluria article
- 7 - PMID 25278549 - Stone composition study
- 8 - PMID 25463995 - Natural hx of asymptomatic stones
- 9 - PMID 26194935 - Tamsulosin for distal stones
- 10 - PMID 25998582 - MET study
- 11 - PMID 11530173 - Lancet 2001 review
- 12 - LabCorp®
- 13 - PMID 7747369 - hematuria study
- 14 - PMID 28763529 - 24-Hour Urine Calcium in the Evaluation and Management of Nephrolithiasis, JAMA (2017)
- 15 - PMID 30527866 - Predictors of Symptomatic Kidney Stone Recurrence After the First and Subsequent Episodes, Mayo Clin Proc (2019)