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Evaluate w/ H&P, including contributing meds & risk factors and perform stone analysis ± urine/blood biochemistry in all first-time stone formers for potential, treatable metabolic d/o & tailored tx.1,2 Ca++ stones are most common type.3 Perform detailed eval in high risk/recurrent stone-formers only [B], per AUA.1 ACP says evidence insufficient that stone composition and blood/urine monitoring reduce recurrence3 Initial tests: - Urine: dipstick & micro, cx
- Blood: Cr, uric acid, ionized Ca++, Na+, K+, CBC, CRP. If no intervention planned, OK to omit Ca++, Na+, K+, CRP, per EUA.2 PTH if hyperparathyroidism suspected [CP]1
- Do not perform “fast & Ca++ load” test to distinguish among types of hypercalciuria [C]1
- Perform/review imaging to quantify stone burden & determine if Ca++ stone [CP]1,2
High-risk stone formers, per EUA2 - Early age of onset (esp children/adolescents)
- Familial stone formation
- Recurrent stone formation
- Short time since last stone episode
- Brushite-containing stones
- Uric-acid and urate stones
- Infection stones
- Solitary kidney (kidney itself does not particularly increase the risk of stone formation, but prevention of stone recurrence is of crucial importance to avoid ARF)
- CKD
- Diseases assoc w/ stone formation: hyperparathyroidism, metabolic syndrome, mineral bone d/o, nephrocalcinosis, PKD, enteric hyperoxaluria due to jejuno-ileal bypass, intestinal resection, Crohn’s disease, malabsorptive conditions, urinary diversion, exocrine pancreatic insufficiency, bariatric surgery, elevated levels vit D, sarcoidosis, spinal cord injury/neurogenic bladder
- Genetic d/o: cystinuria (type A, B, AB), primary hyperoxaluria, renal tubal acidosis type I, 2,9-Didyrdroxyadeniuria, xanthinuria, Lesh-Nyhan syndrome, CF
- Drug-induced stones
- Anatomic abnormalities (medullary sponge kidney, UPJ obstruction, calyceal diverticulum/cyst, ureteral stricture, vesico-uretero-renal reflux, horseshoe kidney, ureterocele
- High ambient temps
- Chronic lead and cadmium exposure
DDx of drug-induced stones: active compounds crystalizing in urine - allopurinol/oxypurinol
- amoxicillin/ampicillin
- ceftriaxone
- quinolones
- ephedrine
- indinavir and other HIV-protease inhibitors
- magnesium trisilicate
- sulphonamides
- triamterene
DDx of drug-induced stones: substances impairing urine composition - acetazolamide
- aluminum magnesium hydroxide
- ascorbic acid
- calcium
- laxatives
- losartan
- methoxyflurane
- orlistat
- vitamin D
- topiramate
- zonisamide
If high-risk, then perform specific metabolic eval based on stone type, per EUA.2 Perform eval when pt is stone-free for 20 days - 24-hr urine while on random diet to test for total volume, pH, Ca, oxalate, uric acid, citrate, Na, K, Cr [EO]1,2
- Additional blood tests guided by stone composition2
Treat based on results of work-up & any identified underlying causes.2 Stop any potential offending drugs. See appropriate stone-type section Advise pt to increase fluid intake to achieve target urine output: - ↑fluids to achieve daily urine output of ≥2 L/day, per ACP,3 whereas AUA1 and EUA2 recommend >2.5-3 L/day intake to achieve urine output 2-2.5 L/day [B] [Strong] w/ goal of specific gravity of urine = <1.010 g/day
- Avoid cola (if Ca++ stone), per ACP,3 (low quality evidence). Water is preferred fluid, per EUA2
- Don’t further increase fluids if contraindicated or pt already at fluid target, per ACP3
Offer diet guidance to prevent recurrence:
- AUA and EAU recommend tailoring diet by stone type and blood/urine chemistries, while ACP3 concludes there’s inadequate evidence
- Balanced diet w/ NL Ca++ (1-1.2 g/day), limited NaCl (4-5 g/day), veg and fiber rich, limited animal protein (0.8-1 g/kg/day) recommended by EAU;2 avoid excessive vitamin supplements2
- ACP3 concludes multicomponent diet studies show mixed results
Modify lifestyle factors as follows:2 - Retain normal BMI
- Get adequate physical activity
- Balance excessive fluid loss
- Reduce EtOH intake
- Reduce soda and calorie-containing fluids
Pharmacologic tx - Per EUA, guided by stone eval and metabolic work-up2
- If recurrent stone with high/relatively high UCa++, offer thiazide1
- If recurrent stone with low/relatively low urinary citrate, offer K+Citrate1
- If recurrent stone w/o metabolic abnormalities, offer thiazide or K+Citrate1
- ACP recommends mono tx w/ thiazide, citrate, or allopurinol only if increased fluids fails to prevent recurrence in pts w/ Ca++ stones [WR] [M]3
Follow-up - Obtain 24-hr urine w/in 6mo of tx to assess response to diet/med tx1
- Thereafter, check 24-hr urine ≥q12mo depending on stone activity1
- If on med tx, monitor blood tests for adverse effects1
- Consider monitoring w/ f/u imaging based on stone activity (XR, US, low-dose CT)
- If no response to tx, repeat stone analysis1
Footnotes 1 AUA 2014 [S/B]. Pearle M, et al. Medical management of kidney stones: AUA Guideline. PDF
2 EAU 2024. Skolarikos A, et al. EAU Guidelines on Urolithiasis. European Association of Urology. Online PDF
3 ACP 2014 [WR/L]. Qaseem A, et al. Dietary and Pharmacologic Management to Prevent Recurrent Nephrolithiasis in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2014. Nov 4;161(9):659-667. Accessed 6/24/24
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Perform blood and urine analyses to identify treatable, metabolic abnormalities.1 Blood tests: Cr, Na, K, Cl, ionized Ca (or total calcium + albumin), PO4, uric acid; if ↑ calcium levels, parathyroid hormone (PTH) and vitamin D. Urine tests: urine volume, urine pH, specific gravity, calcium, oxalate, uric acid, citrate, sodium, and magnesium Advise pt to increase fluid intake to achieve target urine output:
- ↑fluids to achieve daily urine output of ≥2 L/day, per ACP;2 whereas AUA3 and EUA1 recommend >2.5-3 L/day intake to achieve urine output 2-2.5 L/day w/ goal of specific gravity of urine = <1.010 g/day
- Avoid cola (if Ca++ stone), per ACP,2 (low quality evidence). Water is preferred fluid, per EUA1
- Don’t further increase fluids if contraindicated or pt already at fluid target, per ACP2
Offer diet guidance to prevent recurrence: - AUA3 and EAU1 recommend tailoring diet by stone type and blood/urine chemistries, while ACP2 concludes there’s inadequate evidence
- Balanced diet with NL Ca++ (1-1.2 g/day, up to 2 g/day, per AUA), limited NaCl (4-5 g/day), veg and fiber rich (if low urinary citrate [EO]),3 limit animal protein (0.8-1 g/kg/day)1 only if high urinary uric acid [EO];3 avoid excessive vitamin supplements1
- If hyperoxaluria, reduce dietary oxalate [EO][Weak]1,3 and fat1 and maintain nl Ca++ intake [EO]3
- If ↑U urate, reduce purine intake & avoid excessive animal protein intake [Strong]1,3
- If high urinary Na, restrict dietary salt [Strong]1
- ACP2 concludes multicomponent diet studies show mixed results
Modify lifestyle factors as follows:1 - Retain normal BMI
- Get adequate physical activity
- Balance excessive fluid loss
- Reduce EtOH intake
- Reduce soda and calorie-containing fluids
Offer meds only if increased fluids fails and stones are recurrent, per ACP.2 Offer mono tx w/ thiazide, citrate or allopurinol [WR] [M]2 Base tx on results of 24-hr urine test & underlying causes, per AUA/EUA1,3 - If ↑UCa++ (5-8 mmol/day), give alkaline citrate 3-10 g/day or NaBicarb 1.5 g tid [Strong]
- If ↑UCa++ (≥8 mmol/day) , give HCTZ 25-50 mg/day1,3 [Strong] or chlorthalidone 25 g/day1 or indapamide 2.5 mg/day.1 Advise pts on HCTZ to get their skin checked on a regular basis as they have a higher risk of NMSC and some forms of melanoma. Caution in pts with hx skin Ca
- If ↓ urinary citrate (male <1.7 mmol/day, female <1.9 mmol/day), give K+Citrate 3-10 g/day [Strong]1,3
- If ↑U oxalate (>0.5-1 mmol/day) due to hyperabsorption of oxalate or extreme dietary intake, give Ca++ 1-2 g/day (beware excess Ca excretion) [Strong]1 plus Mg++ 200-400 mg/day (low evidence). Consider alkaline citrates to replace citrate loss and raise urine pH [Weak]1
- If ↑U oxalate (>1 mmol/day) due to primary (genetic) hyperoxaluria, give pyridoxin 5 mg/kg/day initial dose, up to 10 mg/kg/day1
- If ↑U urate (>4 mmol/day) without ↑UCa++, give alkaline citrate 3-10 g/day or bicarb 1.5 g tid plus/or allopurinol 100 mg/day [Strong]1
- Per AUA, if ↑U urate and NL UCa++ with recurrent stone, give allopurinol3
- If ↑U urate plus hyperuricemia (>380 µmol/L), give alkaline citrate 3-10 g/day plus allopurinol 100-300 mg/day; 2nd-line tx: febuxostat 80 mg/day [Strong]1
- If ↓UM++ (<3 mmol/day) related to poor dietary intake or chronic diarrhea, give Mg++ 200-400 mg/day
- If recurrent stones w/ no metabolic abnls, then offer HCTZ or K+Citrate3
Follow-up - Obtain 24-hr urine w/in 6mo of tx to assess response to diet/med tx3
- Thereafter, check 24-hr urine ≥q12mo depending on stone activity3
- If on med tx, monitor blood tests for adverse effects3
- Consider monitoring w/ f/u imaging (XR, US, low-dose CT)
- If no response to tx, repeat stone analysis3
Footnotes 1 EAU 2024. Skolarikos A, et al. EAU Guidelines on Urolithiasis. European Association of Urology. Online PDF
2 ACP 2014 [WR/L]. Qaseem A, et al. Dietary and Pharmacologic Management to Prevent Recurrent Nephrolithiasis in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2014. Nov 4;161(9):659-667. Accessed 6/24/24
3 AUA 2014 [S/B]. Pearle M, et al. Medical management of kidney stones: AUA Guideline. PDF
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Perform blood and urine analyses to identify treatable, underlying cause.1 Blood tests: Cr, Na, K, Cl, ionized Ca (or total calcium + albumin), PO4; if ↑ calcium levels, PTH. Urine tests: urine volume, urine pH, specific gravity, calcium, phosphate, & citrate. Ca phosphate stones may be carbonate apatite stones typically assoc w/ infxn or brushite stones assoc w/ HPT and RTA, therefore exclude HPT & RTA. If urine pH>5.8 consider RTA & perform ammonium chloride loading test. If HPT, tx underlying dz w/ surgery Advise pt to increase fluid intake to achieve target urine output: - ↑fluids to achieve daily urine output of ≥2 L/day per ACP;2 whereas AUA3 and EUA1 recommend >2.5-3 L/day intake to achieve urine output 2-2.5L/day w/ goal of specific gravity of urine = <1.010 g/day
- Avoid cola (if Ca++ stone), per ACP,2 (low quality evidence). Water is preferred fluid, per EUA1
- Don’t further increase fluids if contraindicated or pt already at fluid target, per ACP2
Offer diet guidance to prevent recurrence: - AUA3 and EAU1 recommend tailoring diet by stone type and blood/urine chemistries, while ACP2 concludes there’s inadequate evidence
- Balanced diet w/ NL Ca++ (1-1.2 g/day, up to 2 g/day, per AUA), limited NaCl (4-5 g/day), veg and fiber rich (if low urinary citrate),3 limit animal protein (0.8-1 g/kg/day);1 avoid excessive vitamin supplements1
- ACP2 concludes multicomponent diet studies show mixed results
Modify lifestyle factors:1 - Retain normal BMI
- Get adequate physical activity
- Balance excessive fluid loss
- Reduce EtOH intake
- Reduce soda and calorie-containing fluids
Offer meds only if increased fluids fail and stones are recurrent, per ACP.2 Offer mono tx w/ thiazide, citrate or allopurinol [WR] [M]2 Base tx on results of stone type and 24 hr-urine test & underlying causes, per AUA/EUA1,3 Carbonate apatite stones - If hypercalciuria (>8 mmol/24h), give HCTZ 25 mg initially up to 50 mg/day [Strong].1,3 Advise pts on HCTZ to get their skin checked on a regular basis as they have a higher risk of NMSC and some forms of melanoma. Caution in pts w/ hx skin cancer
- If urinary pH >6.5-6.8, exclude RTA, UTI
- If UTI, treat underlying infxn
- If RTA (urine pH>5.4 after ammonium chloride loading test), correct w/ alkaline citrate 3-10 g/day or bicarb 1.5 g tid [Strong] & treat hypercalciuria w/ HCTZ [Strong]
- If RTA and HPT excluded, reduce urinary Ca w/ HCTZ 25 mg initially, up to 50 mg/day
Brushite stones - Exclude HPT and RTA. If HPT or RTA, treat underlying dz
- If hypercalciuria (≥8 mmol/24h), give HCTZ 25-50 mg/day1,3 or chlorthalidone 25 g/day1 or indapamide 2.5 mg/day.1 Advise pts on HCTZ to get their skin checked on a regular basis as they have a higher risk of NMSC and some forms of melanoma. Caution in pts w/ hx skin cancer1
Follow-up - Obtain 24-hr urine w/in 6mo of tx to assess response to diet/med tx3
- Thereafter, check 24-hr urine ≥q12mo depending on stone activity3
- If on med tx, monitor blood tests for adverse effects3
- Consider monitoring w/ f/u imaging (XR, US, low-dose CT)3
- If no response to tx, repeat stone analysis3
Footnotes 1 EAU 2024. Skolarikos A, et al. EAU Guidelines on Urolithiasis. European Association of Urology. Online PDF
2 ACP 2014 [WR/L]. Qaseem A, et al. Dietary and Pharmacologic Management to Prevent Recurrent Nephrolithiasis in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2014. Nov 4;161(9):659-667. Accessed 6/24/24
3 AUA 2014 [S/B]. Pearle M, et al. Medical management of kidney stones: AUA Guideline. PDF
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Uric acid & ammonium urate stones
All uric acid & ammonium urate stone formers are at high risk for recurrence.1 Perform complete hx & blood and urine analyses to identify treatable, underlying cause.1 Blood tests: Cr, uric acid. Urine tests: urine volume, urine pH, specific gravity, and uric acid levels. If ammonium urate stone, check urine cx DDx of uric acid stones (~10% of stones) assoc w/ hyperuricosuria - Dietary excess
- Enzyme defects causing endogenous overproduction
- Myeloproliferative d/o
- Chemo tx
- Gout
- Catabolism
DDx of uric acid stone w/ low urine pH - Decreased urinary ammonium excretion (insulin resistance, gout, ADPKD)
- Increased endogenous acid production (insulin resistance, metabolic syndrome, or exercise-induced lactic acidosis)
- Increased acid intake (high animal protein intake)
- Increased base loss (diarrhea)
DDx of uric acid stone w/ low urine volume - Chronic dehydration
- Excessive respiration/exercise
- Chronic diarrhea
Ammonium urate stones (<1% of all stones) assoc w/ UTI, malabsorption (inflammatory bowel disease and ileostomy diversion or laxative abuse), phosphate deficiency, hypokalemia, and malnutrition Advise pt to increase fluid intake to achieve target urine output: - ↑fluids to achieve daily urine output of ≥2 L/day, per ACP;2 whereas AUA3 and EUA1 recommend >2.5-3 L/day intake to achieve urine output 2-2.5 L/day w/ goal of specific gravity of urine = <1.010 g/day
- Avoid cola (if Ca++ stone), per ACP,2 (low quality evidence). Water is preferred fluid, per EUA1
- Don’t further increase fluids if contraindicated or pt already at fluid target, per ACP2
Offer diet guidance to prevent recurrence: - Balanced diet with NL Ca++ (1-1.2 g/day), limited NaCl (4-5 g/day), veg and fiber rich, limited animal protein (0.8-1 g/kg/day) & low purine diet recommended;1 avoid excessive vitamin supplements1
- If hyperuricosuria, limit non-dairy animal protein [EO]3
- ACP2 concludes multicomponent diet studies show mixed results
Modify lifestyle factors:1
- Retain normal BMI
- Get adequate physical activity
- Balance excessive fluid loss
- Reduce EtOH intake
- Reduce soda and calorie-containing fluids
Specific tx based on results of 24-hr urine test & underlying causes1
- Urine alkalization if first-line tx [Strong]
- If uric acid stone w/ urine pH<6 give alkaline citrate 3010 g/day1,3 or NaBicarb 1.5 g tid.4 Target urine pH 6.2-6.8 for prevention and ph 6.5-7.2 for chemolysis (higher pH may lead to Ca phosphate stone formation)
- If uric acid stone w/ ↑U urate w/o hyperuricemia, give allopurinol 100 mg/day [Strong]1
- If uric acid stone w/ ↑U urate plus hyperuricemia, give allopurinol 100-300 mg/day
- Do not routinely offer allopurinol as first-line tx in pts w/ uric acid stones, consider as adjunct if urine alkalinization fails, per AUA3
- If ammonium urate stone plus urine pH>6.5 w/ UTI, treat w/ abx
- If ammonium urate stone plus urine pH>6.5 w/o UTI, give L-methionine 200-500 mg tid for target urine pH 5.8-6.2
- If ammonium urate stone plus high uric acid excretion, consider allopurinol
Follow-up - Obtain 24-hr urine w/in 6mo of tx to assess response to diet/med tx3
- Thereafter, check 24-hr urine ≥q12mo depending on stone activity3
- If on med tx, monitor blood tests for adverse effects3
- Consider monitoring w/ f/u imaging (XR, US, low-dose CT)3
- If no response to tx, repeat stone analysis3
Footnotes 1 EAU 2024. Skolarikos A, et al. EAU Guidelines on Urolithiasis. European Association of Urology. Online PDF
2 ACP 2014 [WR/L]. Qaseem A, et al. Dietary and Pharmacologic Management to Prevent Recurrent Nephrolithiasis in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2014. Nov 4;161(9):659-667. Accessed 6/24/24
3 AUA 2014 [S/B]. Pearle M, et al. Medical management of kidney stones: AUA Guideline. PDF
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All cystine stone formers (1%-2%) are at high risk for recurrence & for CKD.1 Perform complete hx & blood and urine analyses to identify treatable, underlying cause.1 Blood tests: Cr. Urine tests: urine volume, urine pH, specific gravity, cystine, urine protein. Dz may be asymptomatic so investigate siblings for cystinuria w/ 24-hr quantitative urinary cystine excretion. Abnl >30 mg/day. No role for genotyping in routine mgmt Advise pt to increase fluid intake to achieve target urine output: - ↑fluids to achieve daily urine output of ≥2 L/day per ACP,2 whereas AUA3 and EUA1 recommend >2.5-3 L/day intake to achieve urine output 3 L/day [Strong] w/ goal of specific gravity of urine = <1.010 g/day
- Avoid cola (if Ca++ stone), per ACP,2 (low quality evidence). Water is preferred fluid, per EUA1
- Don’t further increase fluids if contraindicated or pt already at fluid target, per ACP2
Offer diet guidance to prevent recurrence: - Balanced diet w/ NL Ca++ (1-1.2 g/day), limited NaCl ( max 5 g/day),1,3 veg and fiber rich, limited animal protein (0.8-1 g/kg/day)1,3 & low methionine diet (but pts unlikely to comply);1 avoid excessive vitamin supplements1
- ACP2 concludes multicomponent diet studies show mixed results
Modify lifestyle factors:1 - Retain normal BMI
- Get adequate physical activity
- Balance excessive fluid loss
- Reduce EtOH intake
- Reduce soda and calorie-containing fluids
Specific tx - Urine alkalization is first-line. Monitor home urine pH, target pH>7.5-8 to improve cysteine solubility (≥7, per AUA)3
- Use potassium citrates 3-10 mmol bid-tid [3]1,3 to maintain target urine pH >7.5 [Strong]1
- If cysteine excretion <3 mmol/day, consider tiopronin (cystine-binding thiol),1 only if unresponsive to diet changes and urinary alkalization or large recurrent stone burden3
- If cysteine excretion >3 mmol/day, offer tiopronin 250 mg/day, up to 2000 mg/day max [Strong]
Follow-up - Obtain 24-hr urine w/in 6mo of tx to assess response to diet/med tx3
- Thereafter, check 24-hr urine ≥q12mo depending on stone activity3
- If on med tx, monitor blood tests for adverse effects3
- Consider monitoring w/ f/u imaging (XR, US, low-dose CT)3
- If no response to tx, repeat stone analysis3
Footnotes 1 EAU 2024. Skolarikos A, et al. EAU Guidelines on Urolithiasis. European Association of Urology. Online PDF
2 ACP 2014 [WR/L]. Qaseem A, et al. Dietary and Pharmacologic Management to Prevent Recurrent Nephrolithiasis in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2014. Nov 4;161(9):659-667. Accessed 6/24/24
3 AUA 2014 [S/B]. Pearle M, et al. Medical management of kidney stones: AUA Guideline. PDF
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All struvite (infection-stone, 2%-15% of all stones) formers are at high risk for recurrence.1 Perform complete hx & blood and urine analyses to identify treatable, underlying cause.1 Blood tests: Cr. Urine tests: urine pH, urine cx. Infx typically due to urease-producing bacteria (proteus mirabilis in ~50%). If mixed struvite stone, investigate metabolic abnormalities w/ 24-hr urine Risk factors: - Neurogenic bladder
- Spinal cord injury/paralysis
- Continent urinary diversion
- Ileal conduit
- Foreign body
- Stone disease
- Indwelling urinary catheter
- Urethral stricture
- Benign prostatic hyperplasia
- Bladder diverticulum
- Cystocele
- Calyceal diverticulum
- UPJ obstruction
Advise pt to increase fluid intake to achieve target urine output:
- ↑fluids to achieve daily urine output of ≥2 L/day per ACP;2 whereas AUA3 and EUA1 recommend >2.5-3 L/day intake to achieve urine output 2-2.5 L/day w/ goal of specific gravity of urine = <1.010 g/day
- Avoid cola, per ACP.2 Water is preferred fluid, per EUA1
- Don’t further increase fluids if contraindicated or pt already at fluid target, per ACP2
Offer diet guidance to prevent recurrence: - Balanced diet w/ NL Ca++ (1-1.2 g/day), limited NaCl (4-5 g/day), veg and fiber rich, limited animal protein (0.8-1 g/kg/day) & low purine diet recommended by EAU;1 avoid excessive vitamin supplements1
- ACP2 concludes multicomponent diet studies show mixed results
Modify lifestyle factors:1 - Retain normal BMI
- Get adequate physical activity
- Balance excessive fluid loss
- Reduce EtOH intake
- Reduce soda and calorie-containing fluids
Offer specific tx: - Surgical stone removal to reduce ongoing infxn1 [Strong]
- Abx after stone removal1 [Strong]
- Acidify urine and prevent recurrent infxn w/ ammonium chloride 1 g bid-tid [Strong], or methionine 200-500 mg qd-tid [Weak]1
- If mixed stone, treat underlying metabolic cause of stone1
- If severe infxn, consider urease inhibitors (AHA 15 mg/kg/day) if available1 [1b], only after surgical options exhausted, per AUA.3 Side effect profile may limit use; monitor closely for phlebitis, hypercoagulable effects3
Follow-up - Monitor for reinfxn w/ urease-producing organisms and offer strategies to prevent recurrences3
- Consider monitoring w/ f/u imaging (XR, US, low-dose CT)3
Footnotes 1 EAU 2024. Skolarikos A, et al. EAU Guidelines on Urolithiasis. European Association of Urology. Online PDF
2 ACP 2014 [WR/L]. Qaseem A, et al. Dietary and Pharmacologic Management to Prevent Recurrent Nephrolithiasis in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2014. Nov 4;161(9):659-667. Accessed 6/24/24
3 AUA 2014 [S/B]. Pearle M, et al. Medical management of kidney stones: AUA Guideline. PDF
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