- 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 |
|
Renal tubular acidosis type 1 |
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Primary hyperoxaluria |
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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 |
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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 |
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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 |
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Sulpha drugs |
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Topiramate (Topamax®) |
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Triamterene |
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Zonisamide |
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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. It is also found in foods and is absorbed from the intestine when consumed. When oxalate concentrations in the kidneys are high, it can bind calcium and form stones. Calcium oxalate stones are the most common type of kidney stone.
- Dietary oxalate that is consumed and ends up in the intestine may be free or bound to calcium. Free oxalate is absorbed much more readily than oxalate that is bound to calcium. Because of this, deficiencies in intestinal calcium can promote oxalate absorption. These deficiencies may occur through decreased calcium consumption or in the setting of fat malabsorption (e.g. shortened bowel syndrome, bariatric surgery); unabsorbed fats sequester calcium and decrease its availability to bind oxalate.
- Increased dietary oxalate absorption and/or increased production through metabolism can lead to hyperoxaluria and stone formation [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
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- 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
Radiology studies for kidney stones |
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Non-contrast-enhanced CT scan
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Ultrasound
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X-ray (KUB)
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Intravenous pyelogram (IVP)
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Laboratories to consider in patients with kidney stones |
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Urinalysis
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Serum electrolytes, calcium level
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Uric acid, serum
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24-hour urine testing
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Stone analysis
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Parathyroid hormone (PTH)
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Cystine, 24-hour urine
|
- 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
- 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
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Medical expulsive therapy (MET)
|
Shockwave lithotripsy (SWL)
|
Ureterorenoscopy
|
- PREVENTION
AUA Stone Prevention Recommendations |
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All stones
|
Calcium stones
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Uric acid stones
|
Cystine stones
|
Medications to Prevent Kidney Stones |
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Allopurinol
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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)