- 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 overall prevalence of kidney stones in the U.S. has risen from 3% to 5% over the past several decades. By age 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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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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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
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Anatomical abnormalities
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DIETARY RISK FACTORS |
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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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Acetazolamide (Diamox®)
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Allopurinol
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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
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Quinolones antibiotics (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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- STONE RECURRENCE
- Incidence
- After a first kidney stone, the overall risk of recurrence is 40% at 5 years and 75% at 20 years. Annual recurrence rates based on number of stones passed is provided in the table below. [1,2,4]
Annual risk of recurrent kidney stone | |
---|---|
Stones passed | Annual risk of recurrence |
1 | 3.4% |
2 | 7.1% |
3 | 12.1% |
≥ 4 | 17.6% |
- Risk factors
- A cohort study that followed 3364 patients with first symptomatic kidney stone from 1984 to 2017 was used to create a model for predicting recurrence. A calculator based on the model is available at this link - recurrent kidney stone risk predictor
- Factors in the study associated with an increased risk of recurrence 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
- Diameter of the largest kidney stone on imaging [15]
- FACTORS ASSOCIATED WITH STONE FORMATION
- Overview
- Kidney stones form when abnormal concentrations of urinary solutes promote the crystallization of urinary compounds. Most kidney stones form from calcium, and they appear to develop over calcium plaques called Randall's plaques that are present in the renal papilla (see kidney illustration).
- Once a kidney stone forms, it may remain in the renal calyces or pelvis, where it is typically asymptomatic. Some stones eventually pass into the ureters, producing symptoms if large enough (≥ 4 mm). Urinary factors that promote stone formation are presented below.
- Hypercalciuria
- Mechanism
- Elevated urinary calcium levels promote stone formation by increasing the amount of calcium available to bind to oxalate and phosphate [1]
- Causes of hypercalciuria
- 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, an end product of human metabolism that is also found in certain foods, is eliminated in the urine, and high concentrations can bind calcium and form stones. Calcium oxalate stones are the most common type of kidney stone.
- When dietary oxalate reaches the intestine, it exists in two forms: free or bound to calcium. Free oxalate is much more readily absorbed than bound oxalate. Therefore, conditions that reduce intestinal calcium promote oxalate absorption; this is why patients with stones are sometimes told to increase their calcium intake. Unabsorbed luminal fats can also sequester calcium, reducing its ability to bind oxalate. Conditions that decrease fat absorption (e.g. shortened bowel syndrome, pancreatic insufficiency) also increase oxalate absorption. [1,6]
- Causes of hyperoxaluria
- 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 inhibits stone formation through two mechanisms. First, it permits base excretion without raising urinary pH, and second, it forms a soluble complex with calcium that prevents it from forming crystals. Low urinary citrate levels can promote stone formation. [2]
- Causes of hypocitraturia
- Renal tubular acidosis
- Hypokalemia
- Medications (topiramate, acetazolamide)
- Men: > 450 mg/day
- Women: > 550 mg/day
- Hyperuricosuria
- Mechanism
- Uric acid, a byproduct of purine metabolism, can form stones when high concentrations cause it to crystallize. It also promotes calcium stone formation by decreasing the solubility of calcium oxalate. [1,2]
- Causes of hyperuricosuria
- Obesity
- Gout
- ↑ Dietary purines
- Normal urinary uric acid values
- Men: < 800 mg/day
- Women: < 750 mg/day
- Urinary pH
- Mechanism
- Urinary pH has mixed effects on stone formation. An alkaline pH (> 6.2) promotes calcium phosphate stones through supersaturation, but it also increases urinary citrate concentrations, which helps to prevent stones. An acidic 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
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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 found in the renal pelvis and/or calyces (see kidney illustration). They are typically asymptomatic and discovered incidentally during imaging studies for other indications. Results from a small study (N=110) that followed the natural history of 160 asymptomatic renal stones (average size 7 mm) are described below.
- 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 occur when stones in the renal pelvis into the ureter (see kidney illustration). They typically cause symptoms, although very small ones (< 4 mm) may not. Stone size 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 typically asymptomatic, although a small percentage may cause obstructive symptoms leading to flank pain. Ureteral stones 4 mm and larger 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 stones
- Typically used to follow stone progression after diagnosis with a CT scan
- Sensitivity: 44 - 77%
- Specificity: 80 - 87%
- Intravenous pyelogram (IVP)
- During an IVP, the patient is given IV contrast, and X-rays of the kidneys, ureters, and bladder (KUB) are taken. IVP used to be the preferred method for detecting kidney stones, but it has largely been replaced by CT scans. [3]
- Sensitivity: 64 - 87%
- Specificity: 92 - 94% [16]
- Urinalysis
- Symptomatic ureteral stones typically cause gross or microscopic hematuria. In one study (n=140), 85% of patients presenting to the ER with symptomatic stones had hematuria on urinalysis. When a positive urinalysis or a positive urine dipstick was used as criteria, 94% of patients had hematuria. [PMID 7747369]
- Any findings suggestive of infection (e.g. WBCs, bacteria) should be evaluated promptly
- Serum electrolytes, calcium level
- All patients should have serum electrolytes checked. Elevated calcium levels should raise suspicion for hyperparathyroidism, while low bicarbonate and high chloride are consistent with 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 while testing after an initial stone is optional
- The AUA recommends testing while consuming a normal diet that includes the following:
- Urine volume and pH
- Calcium
- Oxalate
- Citrate
- Uric acid
- Sodium - to assess dietary sodium intake
- Potassium - if taking medications, can be used to assess compliance
- Creatinine - to assess compliance with 24-hour collection
- 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 a stone is available, stone analysis should be performed to determine the type of stone
- Parathyroid hormone (PTH)
- Primary hyperparathyroidism should be considered when calcium levels are high or high-normal
- An intact PTH level (active form) should be drawn
- Normal values
- 15 - 65 pg/ml
- Cystine, 24-hour urine
- If cystine stones are suspected, a 24-hour urine for cystine should be performed
- Normal values
- 10 - 100 mg/day [1,5,12,14]
- TREATMENT
- Renal stones (stones in the renal pelvis and/or calyces)
- There are no consensus guidelines for treating renal stones. Recommendations from the European Association of Urology are discussed in the table below.
EAU recommendations for renal stone management |
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Observation
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Shockwave lithotripsy (SWL)
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Percutaneous nephrolithotomy (PNL)
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Ureterorenoscopy
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Urinary alkalinization (uric acid stones)
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- 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)
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Shockwave lithotripsy (SWL)
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Ureterorenoscopy
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- PREVENTION
AUA Stone Prevention Recommendations |
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All stones
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Calcium stones
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Uric acid stones
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Cystine stones
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Medications to Prevent Kidney Stones |
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Allopurinol
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Potassium citrate
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Thiazide diuretics
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- 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)
- 16 - PMID 11310648 - Diagnosis and initial management of kidney stones, Am Fam Physician (2001)