STRATEGIES IN STONE DISEASE MANAGEMENT
From 17th Annual Advances in Urology, presented by the University of South Florida College of Medicine and the H. Lee Moffitt
Cancer Center and Research Institute
Glenn M. Preminger, MD, Professor of Urologic Surgery, Duke University Medical Center, Durham, NC
| MEDICAL MANAGEMENT OF STONE DISEASE
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| Stone disease: recurrent problem; incidence increasing in women; risk factors—family history; body size; initial
stone formation (ie, once first stone forms, risk for additional stone formation increases markedly); progress in
medical management—understanding of factors leading to stone formation; diagnosis of stone disease (ie, detection
of underlying physiologic abnormalities); development of new therapies and treatment strategies
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| Hypercalciuria: most common metabolic abnormality in patients with calcium stone disease; absorptive hypercalciuria
(hyperabsorption of calcium from intestinal tract increases filtered load of calcium, excretion of urinary calcium,
and down-regulation of parathyroid hormone [PTH]); renal-leak hypercalciuria (primary defect occurs in
distal tubule; continued leakage of calcium causes transient decline in serum calcium, stimulates production of vitamin
D and PTH, and increases intestinal calcium absorption and mobilization of calcium from bone); resorptive
hypercalciuria, ie, primary hyperparathyroidism (hyperplastic parathyroid gland stimulates PTH production; subsequent
increase in intestinal calcium absorption and bone resorption increases filtered load of calcium and causes
hypercalciuria); observations—serum calcium levels (normal in renal leak hypercalciuria; elevated in resorptive
hypercalciuria); intestinal calcium absorption (elevated in all 3 forms of hypercalciuria; primary defect in absorptive
hypercalciuria; secondary or compensatory defect in renal-leak and resorptive hypercalciuria)
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| Dietary sodium: plays key role in urinary calcium excretion; oral sodium load—exerts effect similar to that produced
by renal leak of calcium; causes secondary hyperparathyroidism, with subsequent increase in vitamin D synthesis
and intestinal calcium absorption; dietary sodium—major determinant of renal calcium excretion; with every
100-mEq/d increase in dietary and urinary sodium, urinary excretion of calcium increases by 50 mg/dL; caveat—in
patient with hypercalciuria, excessive levels of urinary sodium block hypocalciuric action of thiazide diuretics
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| Dietary calcium and stone formation: calcium-restricted diet—initially used to manage all calcium stone formers;
current data suggest approach may increase risk for stone formation, decrease bone mass, and increase excretion
of urinary oxalate; dietary recommendations for managing patients with recurrent stone disease—maintain majority
of patients on normal calcium diet; maintain moderate calcium restriction in patients with documented absorptive hypercalciuria;
moderate consumption of high-oxalate-containing foods (eg, spinach, tea, chocolate, nuts) in all patients
with calcium stone disease; limit dietary sodium and consumption of red meat in all hypercalciuric patients
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| Calcium supplementation: use increasing as population ages; potential for stone formation varies with individual;
in most premenopausal women—prominent increase in urinary calcium excretion occurs during first month of
supplementation; increase less prominent as therapy continues, PTH function suppressed, and vitamin D down-
regulates); in most postmenopausal women—with blunted production of vitamin D, absorption of supplemental calcium
decreases
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 | When planning calcium supplementation: assess options; standard over-the-counter preparations—contain calcium
carbonate or calcium phosphate; poorly absorbed from intestinal tract; may cause slight increase in risk for stone
formation; combinations of elemental calcium and calcium citrate (eg, Citracal)—better absorbed than calcium carbonate
or calcium phosphate; decrease in saturation of stone-forming salts reduces risk for stone formation; long-
term clinical trial of calcium citrate supplementation in postmenopausal women—detected no significant change in saturation
of calcium oxalate or calcium phosphate and no increase in crystallization of calcium salts; findings suggest
results due mainly to protective effect of citrate
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| Correlation between high acid-ash diet and stone formation
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| Acidosis: any factor producing acidosis—will cause resorption of calcium from bone, increase intestinal calcium absorption,
and decrease calcium resorption from kidney; all 3 factors cause hypercalciuria and negative calcium
balance; acidosis causes hypocitraturia by—decreasing citrate synthesis in kidney; increasing tubular reabsorption
of citrate in distal tubule; combination of hypercalciuria and hypocitraturia—directly related to acidosis; key risk
factor for development of stone disease
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| Observations from dietary study: as participants transitioned from vegan diet to high animal-protein (ie, acid-ash) diet—
pH and citrate levels decreased; calcium, sulfate, and urinary uric acid levels increased; as level of dietary animal
protein increased—saturation of calcium oxalate increased; stone inhibition activity decreased; risk for recurrent
stone formation increased
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| Changes in epidemiologic patterns of stone disease: between 1975 and 2001, peak age of onset of stone disease
decreased from ≈55 yr to ≈30 yr; incidence of stone disease reaching parity among men and women (increased
incidence among women due to changes in diet and lifestyle, and increased obesity)
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| Obesity: compared to normal-sized stone formers, morbidly obese stone formers had—higher incidence of gouty diathesis
(defined by urine pH of <5.5), hyperuricosuria, and hypercalciuria; slightly lower incidence of decreased urinary
volume; point—because urine pH lower, prevalence of uric acid stones markedly different between obese
and normal-sized patients; type 2 diabetes—found in majority of obese patients; causes insulin resistance, which
impairs ammonium excretion, and leads to subsequent decrease in urine pH and increased formation of uric acid
stones; possible options for managing obese patients—dietary modification and weight loss (reverse insulin resistance
and normalize urinary acidity; efficacy limited by difficulty in achieving weight loss); alkali therapy (normalizes
urinary acidity; can achieve marked reduction in stone formation among obese patients)
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| Bariatric surgery: possible cause of stone formation, ie, increasing number of patients who have undergone bariatric
surgery now presenting with stone disease; study comparing bariatric surgery patients to idiopathic stone formers,
normal stone formers, and patients who underwent jejunoileal (JI) bypass surgery—oxalate increased in patients who
underwent bariatric surgery, as opposed to idiopathic and normal stone formers; calcium decreased slightly in patients
who underwent bariatric surgery or JI bypass (ie, calcium bound to malabsorbed fatty acids); citrate levels
declined markedly in patients who underwent bariatric surgery or JI bypass, compared to normal and idiopathic
stone formers; calcium oxalate saturation markedly increased in patients who underwent bariatric surgery, as
compared to other patient groups; conclusions—incidence of malabsorption and hyperoxaluria after current bariatric
surgery increasing; urologists should ask stone patients about history of bariatric surgery or other types of
intestinal surgery that might create increased risk for recurrent stone formation
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| Citrate: most well-known inhibitor of calcium oxalate stones; easily identified; manipulated in urine; lowers saturation
of calcium salts by forming soluble complexes with calcium; inhibits crystallization of calcium salts in urine
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| Hypocitraturia: second most common defect in patient population (hypercalciuria most common); primarily
caused by acidosis; presents—as sole metabolic defect in 5% to 10% of patients; in combination with other metabolic
abnormalities in 50% of patients; factors causing metabolic acidosis and hypocitraturia include—distal renal tubular
acidosis (RTA); chronic diarrhea; excessive physical exercise; high acid-ash diet; potassium depletion from
thiazide diuretics; potassium citrate—reduced stone formation rates in patients with idiopathic hypocitraturia or hypocitraturia
caused by RTA, chronic diarrheal syndrome, and thiazide therapy; available in liquid (eg, Polycitra-K)
and slow-release (eg, Urocit-K pills) preparations; lemonade therapy to increase urinary citrate levels—compared to
other citrus fruits, lemon juice contains higher levels of citrate and magnesium and relatively low levels of calcium
and sodium; data suggest lemonade may be reasonable alternative for increasing urinary citrate excretion in patients
unable or unwilling to take potassium citrate
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| Conclusions: selective medical management significantly reduces rate of stone formation, regardless of underlying
cause of stone disease; future developments—dietary modification increasingly important means of preventing stone
formation; new medications under development; enteric therapy, eg, Oxalobacter formigenes; genetic therapy
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| URETERAL CALCULI: CURRENT MANAGEMENT GUIDELINES
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| Guidelines for managing ureteral calculi (1997)
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| American Urological Association (AUA) approach to guideline selection: extracted data from 327 articles on ureteral
stone disease; categorized recommendations according to standards, guidelines, or options; evaluated—observation;
shock wave lithotripsy (SWL); ureteroscopy; blind basket extraction; percutaneous surgery; open
surgery; performed outcomes analysis that included—stone-free rates; spontaneous passage; number of procedures
per patient; secondary interventions; acute or long-term complications; standardized patient defined as having—
solitary calcium ureteral stone; medical status (including renal function, body habitus, and urinary tract anatomy)
permitting use of any treatment option; access to all accepted treatment modalities
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| Stone-free rates: most quantifiable and meaningful determinant of successful treatment; factors affecting data from
1997—reliance on kidney, ureter, and bladder (KUB) evaluation alone to assess situation (approach probably led
to overestimation of stone-free rates); early SWL technology; stone-free rates derived for—proximal ureteral calculi
(SWL [83%]; ureteroscopy [72%]; percutaneous stone removal [86%]; open ureterolithotomy [97%]); distal
ureteral calculi (SWL [85%]; ureteroscopy [90%]; blind basketing [73%]; open surgery [87%])
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| Standard management recommendations: observation with periodic evaluation initial approach for managing patient
with high probability of spontaneous ureteral stone passage and controlled symptoms (provides opportunity
for spontaneous stone passage); for patient with low probability of ureteral stone passage, provide information on
relative risks and benefits of available treatment options (ensures informed consent); use SWL as first-line treatment
for managing most patients with <1-cm stone in proximal ureter (with advances in ureteroscopic stone removal,
recommendation has changed accordingly)
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| Additional recommendations: improve classification methods and methods for reporting outcomes; develop ability
to predict stone fragmentation response to SWL
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| Improvements in endoscopic ureteral stone management that have changed treatment philosophies
since 1997
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| Introduction of: new and easier to use semirigid ureteroscopes (one design can reach stone in lower pole calyx and
small calyces in peripheral locations within kidney); new 7.5-F flexible ureteroscopes that enable surgeon to
reach stone located anywhere in urinary tract; Nitinol devices—used to remove stones from kidney and ureter;
basket or grasper causes minimal loss of ureteroscope deflection; combination wires—let surgeon get beyond
stones impacted in ureter; ureteral access sheath—safe and effective adjunct to flexible ureteroscopy; easily
passes over working guidewire; reduces costs by decreasing operating time by 20% and eliminating need for balloon
dilation by 80%; markedly reduces intrarenal pressures during procedure and reduces postoperative stricture
formation
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| Intracorporeal lithotripsy: patients essentially cured when they leave hospital; retreatment rates low
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| Holmium laser: multipurpose workhorse for intracorporeal lithotripsy; fragments stones of all compositions; provides
hemostasis; flexible fiber permits use in proximal ureter and kidney; uses drilling action; lower power
lasers—currently available; less expensive and achieve virtually identical stone-free rates as more powerful lasers;
viable option when not also using laser to ablate or enucleate prostate tissue
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| Devices to facilitate intracorporeal lithotripsy: Stone Cone—Nitinol and stainless steel wire configured into expandable
tapered cone; prevents stone migration during Holmium laser or pneumatic stone fragmentation;
covering protects device from laser beam; uncoils as it comes through tight portion of ureter and reforms when
entering dilated portion of ureter (device able to pull stone fragments out of distal ureter); Holmium laser stone
basket—provides better control; traps stone in place during laser fragmentation; prevents proximal migration
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| Factors incorporated into European Association of Urology and AUA guidelines: trial of calcium channel
blocker (nifedipine) or α-blocker (tamsulosin; doxazosin [Cardura]) to facilitate spontaneous stone passage—new recommendation;
approach supported by meta-analysis data; reserved for patients whose pain under control and who do
not have marked obstruction or sepsis
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| Stone-free rates for: proximal ureteral calculi—because of improved instrumentation and stone fragmentation, ureteroscopy
currently achieves significantly better stone-free rates than SWL; laparoscopy has improved percutaneous
stone-free rates and become major treatment alternative to open surgery (technology may eventually be used
to remove larger and more complex ureteral stones); distal ureteral stones—ureteroscopy currently achieves markedly
better stone-free rates (98%-99%) than SWL; panel’s recommendation—because ureteroscopy more invasive
than SWL, patients should be offered choice of undergoing ureteroscopic procedure or SWL
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Suggested Reading
Kang DE et al: Long-term lemonade based dietary manipulation in patients with hypocitraturic nephrolithiasis. J
Urol 177:1358, 2007; Matsumoto ED et al: Effect of high and low calcium diets on stone forming risk during liberal
oxalate intake. J Urol 176:132, 2006; Obligado SH, Goldfarb DS: The association of nephrolithiasis with hypertension
and obesity: a review. Am J. Hypertens, 2008; Pierre S, Preminger GM: Holmium laser for stone
management. World J Urol 25:235, 2007; Porena M et al: Prevention of stone disease. Urol Int 79 Suppl 1:37, 2007;
Preminger GM et al: 2007 guideline for the management of ureteral stones. J Urol 178:2418, 2007; Springhart
WP et al: Use of Stone Cone minimizes stone migration during percutaneous nephrolithotomy. Urology 67:1066,
2006; Weizer et al: New concepts in shock wave lithotripsy. Urol Clin North Am 34:375, 2007.
Educational Objectives
| The goal of this program is to improve management of stone disease. After hearing and assimilating this
program, the clinician will be better able to:
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| 1. Describe factors contributing to the formation of urinary calculi.
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| 2. Discuss changes in the epidemiology of stone disease.
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| 3. Implement appropriate medical management of urinary calculi.
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| 4. Assess current technologic advances in the management of ureteral calculi.
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| 5. Review past and present guidelines for managing ureteral calculi.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee members
to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified
conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business
or commercial interest. For this program, the following has been disclosed: Dr. Preminger is affiliated with Microvasive/Boston
Scientific and Mission Pharmacal. The planning committee reported nothing to disclose.
Acknowledgments
Dr. Preminger gave his scientific lecture at 17th Annual Advances in Urology, presented March 28-31, 2007, in Key West FL, by
the University of South Florida College of Medicine and the H. Lee Moffitt Cancer Center and Research Institute. The Audio-Digest
Foundation thanks Dr. Preminger and the sponsors for their cooperation in the production of this program.
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