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in the clinic
Nephrolithiasis
Screening and Prevention page ITC2-2
Section Editors The content of In the Clinic is drawn from the clinical information and
Christine Laine, MD, MPH education resources of the American College of Physicians (ACP), including
Sankey V. Williams, MD PIER (Physicians’ Information and Education Resource) and MKSAP (Medical
Knowledge and Self-Assessment Program). Annals of Internal Medicine
Physician Writer editors develop In the Clinic from these primary sources in collaboration with
David S. Goldfarb, MD the ACP’s Medical Education and Publishing Division and with the assistance
of science writers and physician writers. Editorial consultants from PIER and
MKSAP provide expert review of the content. Readers who are interested in these
primary resources for more detail can consult http://pier.acponline.org and other
resources referenced in each issue of In the Clinic.
The information contained herein should never be used as a substitute for clinical
judgment.
CME objective: To review the screening and prevention, diagnosis, acute and
preventive treatment, and practice improvement for nephrolithiasis.
A have at least 1 kidney stone. Recent evidence suggests that the preva-
lence of kidney stones is increasing (1), perhaps because they are as-
sociated with hypertension, diabetes, obesity, chronic kidney disease, and the
metabolic syndrome (2, 3). Between 1994 and 2000, outpatient visits for
stone disease increased by 40%, and office visits increased by 43%. Stones re-
cur frequently, with 50% of patients having a second stone within 5 years of
the first one, and 80% having a second stone within 20 years. Kidney stones
are expensive because urologic interventions are required for as many as 20%
of episodes of renal colic. In addition, about 1% of the working population
will be affected by stones in a given year, causing substantial indirect expense
to employers through lost productivity (4). Stones can and should be pre-
vented. Yet many urologists and nephrologists believe that most patients are
not evaluated and not given appropriate advice or therapy, although data on
this issue are lacking.
Screening and
Prevention What factors increase the risk for
nephrolithiasis?
implicated in altering urine com-
position to favor stone formation.
Genetic and environmental influ- Decreased dietary calcium content
ences cause kidney stones. More has been associated with the risk
than 50% of patients in kidney for stones, probably because di-
stone clinics have a first-degree etary calcium can precipitate in-
relative with stones. The most testinal oxalate and prevent its ab-
common urinary phenotype in pa- sorption from the intestine, thus
tients with stones and with family reducing oxalate excretion in the
1. Stamatelou KK, Fran-
cis ME, Jones CA, et histories of stones is hypercalci- urine. Low urine volume leads to
al. Time trends in re-
ported prevalence of uria. Kidney stones in both mem- increased concentration of stone-
kidney stones in the bers of a twin pair occur at twice forming calcium salts and uric
United States: 1976-
1994. Kidney Int. the rate in monozygotic twins ver- acid, so lifeguards, athletes, sol-
2003;63:1817-23.
[PMID: 12675858]
sus dizygotic twins (5). Calcula- diers (especially those deployed to
2. Taylor EN, Stampfer tions based on twin studies hot climates), and others with in-
MJ, Curhan GC. Obe-
sity, weight gain, and estimate that 56% of the stone creased sweating have reduced
the risk of kidney phenotype is accounted for by ge- urine volume and increased rates
stones. JAMA.
2005;293:455-62. netic factors and the rest is envi- of stones. Drivers and teachers
[PMID: 15671430]
3. Daudon M, Traxer O, ronmental. The genes responsible have lower fluid intake and ex-
Conort P, et al. Type 2 for these genetic effects, however, crete more concentrated urine.
diabetes increases
the risk for uric acid have not been identified. Oxalobacter formigenes is an intes-
stones. J Am Soc
Nephrol.
tinal bacterium that metabolizes
2006;17:2026-33. Environmental factors or acquired oxalate. Colonization with Ox-
[PMID: 16775030]
4. Saigal CS, Joyce G,
traits are presumably responsible alobacter may reduce oxalate ab-
Timilsina AR; Urologic for the increase in stone preva- sorption from the colon, reduce
Diseases in America
Project. Direct and in- lence observed in the past 20 urinary oxalate, and protect
direct costs of
nephrolithiasis in an
years. For example, stones are against stones. Antibiotics may
employed popula- strongly associated with weight eliminate this organism, thus in-
tion: opportunity for
disease manage- gain, diabetes, obesity, and the creasing oxalate absorption from
ment? Kidney Int.
2005;68:1808-14.
metabolic syndrome, which are the intestine and oxalate excretion
[PMID: 16164658] occurring more frequently. Dia- into the urine (6). However, it is
5. Goldfarb DS, Fischer
ME, Keich Y, et al. A betes is a strong risk factor for not clear if Oxalobacter prepara-
twin study of genetic both calcium and uric acid stones. tions, which are not yet available
and dietary influ-
ences on nephrolithi- Whether, hypertension is a risk commercially, can prevent kidney
asis: a report from the
Vietnam Era Twin
factor for stones is unclear. In- stones by reducing urinary oxalate
(VET) Registry. Kidney creases in dietary salt, oxalate, and levels. Urinary tract infections as-
Int. 2005;67:1053-61.
[PMID: 15698445] animal protein have been sociated with high urine pH,
© 2009 American College of Physicians ITC2-2 In the Clinic Annals of Internal Medicine 4 August 2009
4 August 2009 Annals of Internal Medicine In the Clinic ITC2-3 © 2009 American College of Physicians
© 2009 American College of Physicians ITC2-4 In the Clinic Annals of Internal Medicine 4 August 2009
sensitivity, 95% specificity, 97% positive pre- chest radiography and measurement
dictive value, and 67% negative predictive of parathyroid hormone may be ap-
value. Computed tomography was also su- propriate. A low serum bicarbonate
perior in detecting nonstone causes of pain. concentration with a urine pH of 6.0
Some stone-forming patients receive or more suggests renal tubular acido-
repeated doses of radiation. In 1 ret- sis (RTA). Hypophosphatemia is seen
rospective study, 108 patients with a in some patients with a renal phos-
primary acute stone episode under- phate leak and calcium stones. High
went an average of 4 radiographic urine pH or pyuria should lead to
examinations during a 1-year period. urine cultures and consideration of
Studies included a mean of 1.2 plain struvite stones.
abdominal films, 1.7 abdominal and How and when should clinicians
pelvic CTs (range 0 to 6), and use specialized laboratory testing
1 IVP (range 0 to 3) during the to determine the cause of
first year of follow-up (12). In an nephrolithiasis?
attempt to minimize radiation expo- More detailed analyses, such as 24-
sure for these patients, new proto- hour urine collections for measure-
cols and imaging techniques for ment of chemistries, are usually
low-dose CT are being developed reserved for patients with recurrent
and have become the standard of stones, children with stones, and
care at many institutions. Low-dose perhaps patients whose first stones
stone-protocol CT seems nearly as are larger and require urologic
effective as standard helical CT for inter vention. Clinicians can use
detection of stones and abdominal these 24-hour urine collections to
pathology in patients who are not identify risk factors for recurrent
morbidly obese (13, 14). stone formation that are then used
When evaluating acute renal colic, to prescribe specific diet and phar-
14. Zagoria RJ, Dixon RL.
obtain a complete blood count, a macologic interventions, although Radiology of urolithi-
asis: implications of
urinalysis, and serum chemistries. no randomized, controlled trials radiation exposure
Complete blood count and urinalysis (RCTs) have shown that this ap- and new imaging
modalities. Adv
are useful for detecting concomitant proach is superior to others (17). Chronic Kidney Dis.
2009;16:48-51.
infection, but hematuria may be ab- Use a laboratory that calculates su- [PMID: 19095205]
sent in acute stone disease. Serum persaturation, which is a ratio of 15. National Institutes of
Health Consensus
chemistries are important for detect- the patient’s ion activity product to Development Con-
ference on Preven-
ing underlying renal dysfunction as- the known solubility product for tion and Treatment
sociated with urinary tract obstruc- the crystal-forming solute in ques- of Kidney Stones.
Bethesda, Maryland,
tion or alterations in extracellular tion. Higher values are associated March 28-30, 1988. J
volume associated with vomiting. with greater stone-forming tenden- Urol. 1989;141:705-
808. [PMID: 2645426]
cy. Supersaturation combines urine 16. Tiselius HG, Acker-
mann D, Alken P, et
Although not recently updated, the volume with concentrations of al; Working Party on
National Institutes of Health consen- calcium, oxalate, citrate, and other Lithiasis, European
Association of Urolo-
sus statement suggested routine labo- variables into a single value that gy. Guidelines on
urolithiasis. Eur Urol.
ratory analyses for first-time stone- suggests the likelihood of recur- 2001;40:362-71.
forming patients to identify risk rence, correlates well with stone [PMID: 11713390]
17. Parks JH, Asplin JR,
factors for recurrent stones (15). More composition (18) and is intuitively Coe FL. Patient ad-
herence to long-
recent guidelines from the European understandable by patients. Deter- term medical treat-
Association of Urology are not sub- mining stone composition by in- ment of kidney
stones. J Urol.
stantially different (16). In the elective frared spectroscopy or X-ray crystal- 2001;166:2057-60.
[PMID: 11696706]
office-based setting, this evaluation lography is inexpensive, aids in 18. Asplin J, Parks J,
should include serum electrolytes, understanding the pathophysiology Lingeman J, et al.
Supersaturation and
blood urea nitrogen, creatinine, calci- of the stone formation, and helps stone composition
in a network of dis-
um, phosphorus, and uric acid. Hy- plan prevention. About 80% of persed treatment
percalcemia suggests sarcoidosis or stones contain calcium, and about sites. J Urol.
1998;159:1821-5.
primary hyperparathyroidism, and 80% of calcium stones are composed [PMID: 9598467]
4 August 2009 Annals of Internal Medicine In the Clinic ITC2-5 © 2009 American College of Physicians
Diagnosis... Computed tomography without contrast is the best method for di-
agnosing the cause of renal colic. Repeated episodes lead to repetitive expo-
sure of patients to radiation, and ultrasonography is preferred for serial follow-
up. Many stones can be diagnosed by plain radiography, and ultrasonography is
good for demonstrating hydronephrosis, although ureteral stones below the
kidney are often missed. When evaluating acute renal colic, obtain a complete
blood count; urinalysis; and levels of serum electrolytes, blood urea nitrogen,
creatinine, calcium, phosphorus, and uric acid to manage the acute episode
and to evaluate the patient for preventive therapy. To guide the choice of pre-
ventive therapy, measure stone composition in all patients and measure urine
supersaturation in 24-hour urine collections of patients with recurrent stones,
children with stones, and perhaps patients whose first stones are large and
require urologic intervention.
Acute
Treatment How should clinicians treat pain
in patients with renal colic?
required less “rescue analgesia,” and had few-
er adverse effects (20).
Opiates or nonsteroidal anti-
Which drugs aid the passage of
inflammatory drugs are used alone
renal stones?
or in combination for moderate-to-
Patients with distal ureteral
severe pain. Ketorolac provides ef-
stones less than 10 mm in diame-
fective pain relief with less sedation ter can be treated with tamsu-
than opiates and, therefore, is pre- losin, an α 1-adrenergic antagonist
ferred for patients who are dis- usually used for benign prostatic
charged from the emergency de- hypertrophy, to aid stone passage.
partment before a stone has passed. Tamsulosin is well-tolerated but
Among opiates, meperidine causes infrequently lowers blood pres-
more nausea and vomiting and is sure, leading to lightheadedness
contraindicated in the presence of or dizziness. A second choice is
decreased kidney function. nifedipine, a calcium-channel
19. Larkin GL, Peacock blocker that presumably causes
WF 4th, Pearl SM, et In a double-blind RCT of ketorolac, 60 mg
al. Efficacy of ketoro- ureteral dilatation and relaxation,
lac tromethamine intramuscular, versus meperidine, 100 to
versus meperidine in
although this drug is more often
150 mg intramuscular based on weight, in 70
the ED treatment of associated with undesirable low-
acute renal colic. Am patients with renal colic, ketorolac gave bet-
J Emerg Med. ter pain relief and led to slightly quicker dis-
ering of blood pressure. These 2
1999;17:6-10.
[PMID: 9928687] charge from the emergency department (19). drugs have not been compared
20. Safdar B, Degutis LC,
In another RCT of 130 patients with renal col- with each other. The trials that
Landry K, et al. Intra-
venous morphine ic, patients received either intravenous mor- used nifedipine for this indica-
plus ketorolac is su-
phine, 5 mg and then another 5 mg after 20 tion also used concomitant gluco-
perior to either drug
alone for treatment minutes; intravenous ketorolac, 15 mg and corticosteroids, such as methyl-
of acute renal colic.
Ann Emerg Med. then another 15 mg after 20 minutes; or a prednisolone. Steroids and
2006;48:173-81, combination of both. The combination was non-steroidal anti-inflammatory
181.e1.
[PMID: 16953530] superior to either drug alone for pain relief, drugs may reduce stone-induced
© 2009 American College of Physicians ITC2-6 In the Clinic Annals of Internal Medicine 4 August 2009
ureteral edema to aid stone pas- occur. Urinary tract infection with
sage. Whether nifedipine and obstruction is the most urgent in-
steroids are effective separately dication for hospitalization and
or only together has not been urologic consultation.
established.
When should clinicians consider
When should clinicians hospitalize lithotripsy, surgery, or other
patients with nephrolithiasis? interventions in the acute
Consider hospitalization for pa- management of patients with
tients with stones larger than nephrolithiasis?
5 mm if parenteral therapy is re- Usually, urologists will decide
quired to manage pain. Admit pa- whether a procedure will be done
tients with stones of any size if and which procedure will be used.
pain or nausea and vomiting can- The choice often depends on the
not be managed in the outpatient urologist’s assessment and skills and
setting. Smaller stones (<5 mm) the patient’s preference. The AUA’s
are likely to pass without surgical Ureteral Stones Clinical Guidelines
intervention, whereas larger stones Panel and the European Association
are more likely to be associated of Urology (22) recommend extra-
with a prolonged course, more corporeal shock wave lithotripsy
pain, and a lower likelihood of (ESWL) as first-line treatment for
spontaneous passage. stones no larger than 1 cm in diam-
A meta-analysis of 327 studies by the Ureter-
eter in the proximal ureter;
al Stones Clinical Guidelines Panel convened ureteroscopy and percutaneous
by the American Urologic Association (AUA) nephrolithotomy are acceptable al-
found that 98% of smaller stones (<5 mm) ternatives, especially if ESWL is
passed spontaneously. Distal ureteral stones inappropriate or fails. For stones
passed more frequently than proximal larger than 1 cm in diameter in the
ureteral stones (21). proximal ureter, consider percuta-
neous nephrolithotomy or
An obstructed and infected uri-
ureteroscopy. For distal ureteral
nary tract is an absolute indication
stones no larger than 1 cm in diam-
for emergent intervention, because
eter, choose ESWL or ureteroscopy
this condition can lead to urosep-
instead of blind basketing without
sis and irreversible renal parenchy-
fluoroscopy. For distal ureteral
mal damage. Concomitant urinary
stones greater than 1 cm, perform
tract infection is suggested by
ESWL or ureteroscopy; although
fever or pyuria (>5 to 20 leuko-
for larger stones, ureteroscopy may
cytes per high-powered field) or
be more appropriate because ESWL
substantial leukocytosis. Also, ad-
must fragment stones into smaller
mit patients with bilateral ob-
struction or obstruction in a soli- pieces to be successful. Ureteroscopy
tary kidney if decreased kidney may lead to better clearance of stone 21. Segura JW, Pre-
function is evident. Administer fragments, which minimizes stone minger GM, Assimos
DG, et al. Ureteral
antibiotics promptly on the basis recurrence. For patients with stones Stones Clinical
of local sensitivity patterns. who are undergoing ESWL, consid- Guidelines Panel
summary report on
er subsequent treatment with tam- the management of
ureteral calculi. The
When should clinicians consult a sulosin to aid passage of stone American Urological
urologist or other specialist? fragments. The AUA recommenda- Association. J Urol.
1997;158:1915-21.
Consult a urologist for stones tions regarding the management of [PMID: 9334635]
22. Preminger GM,
larger than 5 mm or those that staghorn calculi suggest that percu- Tiselius HG, Assimos
prevent patients from conducting taneous nephrolithotomy should be DG, et al; EAU/AUA
Nephrolithiasis
their normal activities. Consult a the first treatment used for most Guideline Panel.
2007 guideline for
urologist for stone removal when patients, and that ESWL mono- the management of
the likelihood of spontaneous pas- therapy should not be used for most ureteral calculi. J
Urol. 2007;178:2418-
sage is low or when complications patients. 34. [PMID: 17993340]
4 August 2009 Annals of Internal Medicine In the Clinic ITC2-7 © 2009 American College of Physicians
Preventive
Treatment What is the role of fluid intake
and diet in the preventive
episodic condition that is not usually
life-threatening. Despite ample epi-
treatment of patients with demiologic data linking diet and
nephrolithiasis? stones, only 1 RCT with positive re-
Advise patients at high risk for re- sults has been published. Few data
current stone disease to drink at are available regarding the willing-
least 2 to 2.5 L/d (68 to 85 oz) to ness and ability of stone-forming pa-
maintain urine volume of at least tients to adhere to a diet. Epidemio-
2 L. Emphasize higher intake to logic evidence demonstrates that
achieve the same urine output in men and women with greater calci-
people who are physically active um intake have fewer stones (23,
(for example, athletes), work in hot 24). This effect is most likely due to
climates (for example, lifeguards), the ability of dietary calcium to bind
have diseases associated with stone oxalate in the intestine and prevent
formation (for example, distal its absorption.
RTA, medullary sponge kidney, These observational data were supported
polycystic kidney disease), or have by 1 RCT. Italian men (n = 120) with hyper-
increased bowel fluid losses (for ex- calciuria and recurrent calcium oxalate
ample, from ileostomy or other stones were randomly assigned to 1 of 2
bowel disorders). Increased fluid regimens. One regimen restricted calcium
intake leads to urine dilution and a intake to 400 mg/d, and the other recom-
decrease in urine supersaturation of mended a “normal” calcium intake of 1200
23. Curhan GC, Willett
mg/d and restricted animal protein (52 g)
WC, Rimm EB, et al. poorly soluble salts, such as calcium
A prospective study and salt intake (50 mmol) (Table 1). In both
of dietary calcium oxalate, calcium phosphate, and groups, participants were counseled to re-
and other nutrients
and the risk of cystine. Urine volume may be less strict oxalate intake. At the end of 5 years,
symptomatic kidney important in uric acid stone– the group on the high-calcium, low-salt,
stones. N Engl J
Med. 1993;328:833- forming patients who successfully low–animal-protein diet had a 50% lower
8. [PMID: 8441427]
24. Curhan GC. Dietary alkalinize the urine. Increasing flu- rate of stone recurrence when compared
calcium, dietary pro- id intake may be especially difficult with the group on the low-calcium diet.
tein, and kidney
stone formation. for men with benign prostatic hy- The effect was attributed to increased cal-
Miner Electrolyte
pertrophy or for other persons with cium ingestion leading to reduced urinary
Metab. 1997;23:261-
oxalate excretion while sodium restriction
4. [PMID: 9387129] bladder disorders. These patients limited urinary calcium excretion. Protein
25. Borghi L, Schianchi
T, Meschi T, et al. may benefit from dietary alteration restriction may have also played a part by
Comparison of two
diets for the preven- and drug therapy. increasing citrate excretion and contribut-
tion of recurrent ing to the reduction of calcium excretion
stones in idiopathic
hypercalciuria. N
Diet is an attractive therapy to many (both of which may occur with less net
Engl J Med. patients with stones who may be re- acid excretion, suggested by the modest
2002;346:77-84.
[PMID: 11784873] luctant to take medications for an decrease in urine sulfate excretion) (9).
© 2009 American College of Physicians ITC2-8 In the Clinic Annals of Internal Medicine 4 August 2009
Although bone mineral density was several RCTs have demonstrated that
not measured, one would anticipate thiazides prevent recurrent calcium
that the group on the higher calcium stones. At 3 years, stones recurred in
intake would have had less deminer- 50% to 60% of patients receiving
alization than the other group. This placebo and 15% to 30% of patients
possibility is another reason not to receiving thiazide. Studies with less
restrict calcium in patients with hy- than 2 years of treatment did not
percalciuria, who have reductions in show benefit (26, 27). Thiazides in-
bone mineral density and more fre- clude chlorthalidone, indapamide,
quent bone fractures (25). and hydrochlorothiazide. The first 2
are usually taken once a day, whereas
Patients with uric acid stones should hydrochlorothiazide is best taken
limit animal protein intake, which twice a day. Thiazides reduce urinary
reduces the amount of alkali needed calcium by stimulating renal calcium
to increase urine pH, but diet alone reabsorption and may stimulate bone
has not been shown to prevent uric to incorporate calcium. Because hy-
acid stones. People with cystine percalciuria is linked to decreases in
stones should limit animal protein bone mineral density (BMD), it is
and salt intake to increase urine pH useful that thiazides are also associat-
and reduce cystine excretion. ed with increases in BMD (28).
Because thiazides can cause hypo-
What drug therapy should kalemia, which lowers citrate excre-
clinicians consider to prevent tion, most patients receiving thiazides
recurrent nephrolithiasis, and how should be supplemented twice a day
does it differ in patients with with potassium citrate or given potas-
different types of stone disease? sium-sparing drugs, such as amiloride
Table 2 lists drug therapy for stone or spironolactone. Avoid triamterene,
prevention. The effectiveness of this because it is poorly soluble.
or other diets in patients with other
risk factors for stones, or other types Citrate is an inhibitor of the crystal-
of stones, has not been tested. Thi- lization of calcium oxalate and calci-
azides lower urinary calcium excretion um phosphate. Use citrate supple-
in patients with hypercalciuria, and mentation for secondary prevention
4 August 2009 Annals of Internal Medicine In the Clinic ITC2-9 © 2009 American College of Physicians
Potassium citrate Citrate forms soluble 20 to 30 mEq bid to Increases urinary GI intolerance, especially in elderly patients or patients
complexes with tid. Once-daily citrate excretion and with GERD (heartburn, nausea). Potential for hyper-
calcium; inhibits crystal dosing may be prevents calcium kalemia in patients with renal insufficiency or taking
growth and aggregation. effective for some stone recurrence. ACE inhibitors. For secondary prevention of kidney
For uric acid and cystine patients if citrate Increased urine pH stones. Comes in longer-acting tablets or dissolvable
stones, citrate increases excretion or urine dissolves uric acid crystal forms. Sodium citrate preparations may have
urine pH after pH increases crystals and better GI tolerance for some but are not clearly
metabolism to adequately. Dosing solubilizes cystine. effective in preventing stone recurrence.
bicarbonate by liver tid may be appro- At urine pH values
priate for dissolution >7.0, solubility of
of uric acid or cystine in urine in-
cystine stones. creases dramatically.
Allopurinol Xanthine oxidase 300 mg qd, reduce Prevents stone Rare allergy, eosinophilia, interstitial nephritis, the
inhibitor reduces with decreased GFR recurrence in Stevens–Johnson syndrome. For secondary prevention
urinary uric acid patients with of kidney stones. For uric acid stones, urinary
excretion hyperuricosuria and alkalinization with citrate supplementation is
normocalciuria. usually more important than reducing uricosuria.
Prevents gout.
Adjunctive to
potassium citrate
for uric acid stones.
Organic marine Seaweed-derived 9 tablets per day Well-tolerated Only anecdotal reports exist of efficacy for reducing
hydrocolloid hydrocolloid binds nutraceutical agent urinary oxalate excretion.* Decreased urinary oxalate
(Ox-Absorb) oxalate in intestinal for treatment of in patients with bowel disorders. No trials
lumen and prevents hyperoxaluria. demonstrating decreased stone recurrence. Both
absorption Useful for enteric or calcium citrate and cholestyramine may have
dietary hyperoxaluria. some effect to reduce intestinal oxalate absorption.
Sodium cellulose Ion-exchange resin 10 g/d in divided Reduction of Causes negative calcium balance and decreased
phosphate which binds dietary doses hypercalciuria bone mineral density, similar to dietary calcium
calcium in intestinal restriction. Can reduce urinary magnesium excretion
lumen and reduces and increase urinary oxalate. No randomized trials
urinary calcium excretion have been performed with stone formation as an
outcome, and questions about long-term safety be-
cause of risk for osteoporosis have led to very infre-
quent use of this preparation.†
Orthophosphate Reduces serum 4 tablets bid. Each Neutral potassium Associated acid and sodium loads limit efficacy in
1,25-dihydroxyvitamin D tablet contains phosphate may reducing calciuria and protecting bone density.
concentration and phosphate, 155 mg, directly inhibit bone Rapid-release forms are associated with abdominal
intestinal calcium and potassium, resorption while cramping and diarrhea. Slow-release potassium
absorption; increases 8 mEq. reducing calcium phosphate may be better tolerated. A randomized,
urinary excretion of absorption and controlled trial of phosphate acid did not prevent
pyrophosphate, an urinary excretion stones‡. A slow-release preparation of neutral
inhibitor of calcium potassium phosphate was safe and effective in
oxalate crystal formation improving urinary chemistries and preventing bone re-
sorption in a short randomized trial, although efficacy
in preventing stones was not studied. It may overcome
the disadvantages of acid and sodium phosphate
preparations, but is not yet commercially available.§
© 2009 American College of Physicians ITC2-10 In the Clinic Annals of Internal Medicine 4 August 2009
Magnesium Magnesium inhibits Patients with bowel Diarrhea. Efficacy of magnesium supplementation in
supplementation calcium oxalate crystal disease often have randomized, controlled trials is lacking. It should
formation and growth decreased urinary probably be reserved for patients with low urinary
in vitro. Hypomagne- magnesium magnesium excretion.||
semia may reduce excretion, which
urinary citrate excretion. might contribute
to stone formation
Acetohydroxamic Inhibits activity of 250 mg bid for 3 to Inhibition of urease Headache is a frequent side effect to limit long-term
acid urease, the bacterial 4 weeks; if tolerated, decreases urinary use. 20% to 30% of patients are unable to tolerate
enzyme responsible for increase dose to alkalinization and use of the drug. Other side effects include mild
causing struvite stones 250 mg tid precipitation of hemolytic anemia, GI upset, tremulousness, dysgeusia,
struvite anxiety. Surgical removal of all struvite stone frag-
ments is the most effective therapy and preferable to
this drug. Acetohydroxamic acid does reduce stone
growth but not necessarily stone events. Adequate uri-
nary levels of the drug are not achieved if serum crea-
tinine is >176.8 mmol/L (2 mg/dL).¶
Tiopronin Thiol drug reduces the 500 to 1000 mg/d, Solubilizes cystine Rash, proteinuria, GI intolerance, pruritus, intrahepatic
(α-mercapto disulfhydryl bridge of occasionally up to cholestasis, wrinkling and friability of the skin,
propionylglycine) cystine to form the 3000 mg/d hypogeusia, vitamin B6 deficiency. Limited sources
more soluble suggest a somewhat better side effect profile than
drug–cysteine complex D-penicillamine. Administer vitamin B6, 50 mg/d.
Check LFTs and CBC every mo when initiating therapy,
then every 3 mo.**
D-penicillamine Thiol drug reduces the 1000 to 2000 mg/d Solubilizes cystine Bone marrow depression with leukopenia,
disulfhydryl bridge of thrombocytopenia. Agranulocytosis, aplastic anemia,
cystine to form the pancytopenia, and sideroblastic anemia can be fatal.
more soluble Proteinuria, dysgeusia, fever, rash, vitamin B6
drug–cysteine complex deficiency, aphthous stomatitis. Give vitamin B6,
50 mg/d. Check LFTs and CBC every mo when initiating
therapy, then every 3 mo.
ACE = angiotensin-converting enzyme; bid = twice daily; BID = twice daily; CBC = complete blood count; GERD = gastroesophageal reflux disease; GFR =
glomerular filtration rate; GI = gastrointestinal; LFT = liver function tests; qd = once daily; tid = three times daily.
* Lindsjö M, Fellström B, Ljunghall S, et al. Treatment of enteric hyperoxaluria with calcium-containing organic marine hydrocolloid. Lancet. 1989;2:701-
4. [PMID: 2570957]
†
Breslau NA. Pathogenesis and management of hypercalciuric nephrolithiasis. Miner Electrolyte Metab. 1994;20:328-39. [PMID: 7783695]
Pak CY. A cautious use of sodium cellulose phosphate in the management of calcium nephrolithiasis. Invest Urol. 1981;19:187-90. [PMID: 7298289]
‡
Ettinger B. Recurrent nephrolithiasis: natural history and effect of phosphate therapy. A double-blind controlled study. Am J Med. 1976;61:200-6.
[PMID: 782240]
§
Breslau NA, Heller HJ, Reza-Albarrán AA, et al. Physiological effects of slow release potassium phosphate for absorptive hypercalciuria: a randomized
double-blind trial. J Urol. 1998;160:664-8. [PMID: 9720517]
||
Reungjui S, Prasongwatana V, Premgamone A, et al. Magnesium status of patients with renal stones and its effect on urinary citrate excretion. BJU Int.
2002;90:635-9. [PMID: 12410738]
¶
Wang LP, Wong HY, Griffith DP. Treatment options in struvite stones. Urol Clin North Am. 1997;24:149-62. [PMID: 9048858]
** Pak CY, Fuller C, Sakhaee K, et al. Management of cystine nephrolithiasis with alpha-mercaptopropionylglycine. J Urol. 1986;136:1003-8. [PMID:
3534301]
of calcium stones in patients with re- patient per year in the treated group
duced urinary citrate. Low urine compared with no change in the
citrate occurs with chronic metabolic placebo group (29). Potassium citrate
acidosis, which can be caused by supplementation might also be
bowel disease, RTA, and high pro- useful in “unselected” calcium stone–
tein intake but is often idiopathic. In forming patients regardless of uri-
29. Barcelo P, Wuhl O,
an RCT of potassium citrate in pa- nary citrate excretion. Citrate Servitge E, et al. Ran-
tients with calcium stones and low supplementation is associated with domized double-
blind study of potas-
urinary citrate, treatment with potas- an increase in urine pH. In calcium sium citrate in
idiopathic hypocitra-
sium citrate, 30 to 60 mEq/d in stone disease, this increase in urine turic calcium
divided doses, led to reduction of pH might lead to an increase in nephrolithiasis. J
Urol. 1993;150:1761-
stone formation from 1.2 to 0.1 per urine supersaturation of calcium 4. [PMID: 8230497]
4 August 2009 Annals of Internal Medicine In the Clinic ITC2-11 © 2009 American College of Physicians
© 2009 American College of Physicians ITC2-12 In the Clinic Annals of Internal Medicine 4 August 2009
4 August 2009 Annals of Internal Medicine In the Clinic ITC2-13 © 2009 American College of Physicians
Practice
Improvement What do professional
organizations recommend
How should clinicians educate
patients with nephrolithiasis?
regarding the care of patients Patients can be referred to the Web
with nephrolithiasis? resources listed in the Toolkit. A
The National Institutes of Health useful book about preventing
49. Segura JW, Pre-
minger GM, Assimos last published a consensus docu- stones, written for lay people and
DG, et al. ment in 1980 (14). The recommen- co-authored by a nephrologist,
Nephrolithiasis Clini-
cal Guidelines Panel dations made at that time have not a urologist and a dietician, is
summary report on
the management of
evolved substantially (48). Surgical available (51).
staghorn calculi. The therapy has improved dramatically,
American Urological
Association radiologic imaging is vastly superi-
Nephrolithiasis Clini-
cal Guidelines Panel.
or, but medical therapy has not
J Urol. advanced very much, with the ex-
1994;151:1648-51.
[PMID: 8189589]
ception of not restricting calcium
50. Preminger GM, intake in calcium stone–forming
Tiselius HG, Assimos
DG, et al; American patients. The AUA guidelines ad-
Urological Associa-
tion Education and
dress surgical management rather
Research, Inc. 2007 than preventive therapy (20, 49). In
Guideline for the
management of 2007, the American Urological As-
ureteral calculi. Eur sociation and the European Associ-
Urol. 2007;52:1610-
31. [PMID: 18074433] ation of Urology cooperated to
51. Rodman JS, Sosa RE,
Seidman C, et al. No
create joint recommendations for
More Kidney Stones. managing patients with suspected
Hoboken, NJ: J Wi-
ley; 2007. kidney stones (21, 50).
in the clinic
in the clinic PIER Modules
www.pier.acponline.org
Tool Kit
Access the PIER module on Nephrolithiasis.
Patient Information
www.urologyhealth.org/adult/index.cfm?cat=12&topic=105
American Urological Association: Management of Ureteral Stones
www.urologyhealth.org/adult/index.cfm?cat=12&topic=102
Nephrolithiasis American Urological Association: Medical Management of Stone Disease
www.urologyhealth.org/adult/index.cfm?cat=12&topic=132
American Urological Association: Surgical Management of Stones
kidney.niddk.nih.gov/kudiseases/pubs/stonesadults/index.htm
National Institute of Diabetes and Digestive and Kidney Diseases:
Kidney Stones in Adults
kidney.niddk.nih.gov/kudiseases/pubs/stones_ez/index.htm
National Institute of Diabetes and Digestive and Kidney Diseases:
What I Need to Know About Kidney Stones
kidney.niddk.nih.gov/spanish/pubs/stones_ez/index.htm
National Institute of Diabetes and Digestive and Kidney Diseases:
What I Need to Know About Kidney Stones (Spanish)
www.kidney.org/Atoz/atozItem.cfm?id=84
National Kidney Foundation
Clinical Guidelines
www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=uc
Access the American Urological Association guidelines on ureteral calculi.
www.uroweb.org/fileadmin/tx_eauguidelines/2008/Full/17%20Urolithiasis.pdf
Access the European Association of Urology guidelines on urolithiasis.
© 2009 American College of Physicians ITC2-14 In the Clinic Annals of Internal Medicine 4 August 2009
Shock Waves
• A machine sends shock waves to the kidney stone. This
breaks the stone into small pieces that pass out of your
body with your urine. This method is called extracorpo-
real shock wave lithotripsy (ESWL). Lithotripsy is a Greek
word that means stone crushing.
• With one type of shock machine, you sit in a tub of
water. With the other type, you lie on a table. A tech-
nician directs the sound waves to the stone.
Tunnel Surgery
Patient Information
• The doctor makes a small cut on your back. A special
instrument passes through a narrow tunnel to the Points to Remember
stone and removes it. This method is called percuta-
neous nephrolithotomy. • Most stones pass out of the body without a doctor’s
help.
Ureteroscope • See your doctor if you have severe pain in your back
or side that will not go away.
• A ureteroscope looks like a long wire. The doctor puts
it into the patient’s urethra through the bladder and • See your doctor if you have blood in your urine—the
up the ureter, and directs it to the stone. This is done urine will look pink.
using a camera that lets the doctor see the stone. A • In the future, after the stone is gone, drink lots of wa-
tiny cage catches the stone and pulls it out, or the ter to prevent more kidney stones from forming.
doctor may be able to destroy it with a laser. • Talk with your doctor about other ways to keep from
• Ask your doctor which method is right for you. getting more stones.
CME Questions
1. In a patient with hypercalciuric several years, she has had dry eyes and formed in the past 6 months; however,
nephrolithiasis, which of the following dry mouth. She also describes symptoms hypokalemia has developed (serum
is associated with increased risk for of Raynaud’s phenomenon. Crohn dis- potassium level, 2.9 mmol/L).
stone formation? ease was diagnosed 10 years ago; the Taking the hypokalemia into account,
A. Low-sodium diet patient is currently asymptomatic and what therapy should the patient receive
passes 1 formed stool daily. She takes for hypercalciuric stone disease?
B. Low-calcium diet
no medications. There is no family histo-
C. Low-oxalate diet A. High-potassium diet plus
ry of renal stone disease.
D. Low-protein diet hydrochlorothiazide
E. Low-purine diet On examination, the patient is alert and
B. Acetazolamide plus
healthy. Blood pressure is 115/74 mm
hydrochlorothiazide
2. A 39-year-old male carpenter presents Hg, pulse rate is 72/min, and tempera-
C. Magnesium oxide plus
to the emergency department with a ture is 37°C (98.6°F). The skin is clear,
and the joints are normal. The lungs are hydrochlorothiazide
4-hour history of gradually worsening
right flank and right upper quadrant clear. Cardiac examination shows regu- D. Amiloride plus
pain radiating to the right lower quad- lar sinus rhythm and no murmur. The hydrochlorothiazide
rant and into the right testicle. He vom- liver and spleen are not palpable, and
5. A 64-year-old woman comes for a fol-
its once shortly after arrival. He does the abdomen is not tender.
low-up visit after an episode of kidney
not have fever or chills but has mild Plain abdominal radiography shows stones 2 weeks ago. During the episode,
dysuria. multiple calcifications overlying both she went to the emergency department
On examination, the patient is restless renal shadows. and was treated with nonsteroidal anti-
because of pain. Blood pressure is Laboratory study results are as follows: inflammatory drugs and fluids. Spiral
145/89 mm Hg, pulse rate is 92/min, hemoglobin, 13.2 g/dL; hematocrit, abdominal CT performed at that time
and temperature is 37°C (98.6°F). Ab- 39%; leukocyte count, 7.4 × 109 revealed a 3-mm nonobstructing calcu-
dominal examination reveals mild right cells/µL; blood urea nitrogen, 6.4 lus in the midleft ureter. She also has
costovertebral angle tenderness, but no mmol/L (18 mg/dL); serum creatinine, osteoporosis.
abdominal guarding. Genitalia are nor- 79.56 µmol/L (0.9 mg/dL); serum sodi- Laboratory study results are as follows:
mal. The serum creatinine concentration um, 138 mmol/L; serum potassium, blood urea nitrogen, 7.5 mmol/L
is 79.56 µmol/L (0.9 mg/dL). Urinalysis 2.8 mmol/L; serum chloride, (21 mg/dL); uric acid, 0.3 mmol/L;
shows a specific gravity of 1.025, 3+ 109 mmol/L; serum bicarbonate, creatinine, 141.47 µmol/L (1.6 mg/dL);
hematuria, and no proteinuria. Urine 19 mmol/L; serum calcium, 2.3 mmol/L sodium, 137 mmol/L; potassium,
microscopy reveals more than 50 ery- (9.1 mg/dL); serum phosphorus, 3.2 3.8 mmol/L; chloride, 105 mmol/L;
throcytes/hpf, 3 to 5 leukocytes/hpf, mg/dL; urinalysis: pH, 6.0, specific gravi- bicarbonate, 24 mmol/L; albumin,
and occasional calcium oxalate crystals. ty, 1.020, trace hematuria, no protein- 4.1 g/L; calcium, 2.87 mmol/L
You suspect that a uria; arterial blood: pH, 7.29. (11.5 mg/dL); phosphorus, 0.39 mmol/L
renal stone is causing the colicky pain
What is the most likely cause of this pa- (1.2 mg/dL); urinalysis: pH, 5.5,
and hematuria.
tient’s renal stone disease? 1+ blood.
What radiologic procedure will best
A. Idiopathic hypercalciuria Which of the following is the most
confirm the diagnosis?
B. Primary hyperthyroidism appropriate management for this pa-
A. Plain radiography of the abdomen C. Distal renal tubular acidosis tient’s kidney stones?
B. Intravenous pyelography D. Enteric hyperoxaluria A. Decrease dietary calcium to
C. Renal ultrasonography <1 g/d
D. Noncontrast spiral computed 4. A 40-year-old man has recurrent B. Refer for parathyroidectomy
tomography nephrolithiasis due to idiopathic hyper- C. Refer for stone removal
calciuria. He has had more than 40 cal-
3. A 28-year-old woman presents for eval- D. Initiate potassium citrate therapy
cium oxalate stones in the past 5 years.
uation of recurrent kidney stones that E. Observe
He starts taking hydrochlorothiazide
she says “contain calcium.” She esti- therapy and a low-sodium diet. During
mates that she has passed four stones treatment, his 24-hour urinary calcium
during the past 4 years. She currently concentration decreases from 385 mg/d
has no symptoms of renal colic. For to 180 mg/d. No new stones have
Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP). Go to www.annals.org/intheclinic/
to obtain up to 1.5 CME credits, to view explanations for correct answers, or to purchase the complete MKSAP program.
© 2009 American College of Physicians ITC2-16 In the Clinic Annals of Internal Medicine 4 August 2009