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Prevention of recurrent calcium stones

Burton D Rose, MD
Gary Curhan, MD, ScD

UpToDate performs a continuous review of over 330 journals and other resources. Updates are added
as important new information is published. The literature review for version 13.2 is current through
April 2005; this topic was last changed on May 13, 2005.

INTRODUCTION – Chronic prevention of recurrent calcium stones (which are


usually composed primarily of calcium oxalate) is aimed at decreasing the
concentrations of the reactants (calcium and oxalate) and at increasing the
concentrations of inhibitors of stone formation, such as citrate.

Achieving these goals involves both dietary modification and the administration of
appropriate drugs. Medical therapy is usually limited to recurrent stone formers,
which includes patients in whom helical CT on initial symptom presentation shows
evidence of more than one stone. Those with a single kidney stone are encouraged
to increase their fluid intake and are monitored periodically (usually by renal
ultrasonography) for new stone formation (show radiograph 1). (See "The first
kidney stone and asymptomatic nephrolithiasis").

The managment of patients with recurrent calcium stones will be reviewed here.
The management of patients with active stone disease in whom the stone
composition is not known is discussed separately. (See "Evaluation of the patient
with established nephrolithiasis and treatment if stone composition is unknown").

MONITORING OF RESPONSE – The response to dietary or drug therapy is


monitored by repeat 24-hour urine collections as performed in the initial
evaluation of the patient with established stone disease. (See "Evaluation of the
patient with established nephrolithiasis and treatment if stone composition is
unknown", section on 24-hour urine collections).

The goal of therapy is to reverse the abnormalities detected during the initial
work-up (eg, low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia and
hyperoxaluria). We routinely obtain at least one and preferably two 24-hour urine
collections at six to eight weeks after therapy has begun. The 24 hour urine should
be rechecked 4 to 8 weeks after recommendations are implemented to assess the
impact of the intervention; if the desired changes have taken place, repeat values
are obtained at yearly intervals [1]. If biochemical abnormalities persist, further
therapy is required.

It is important to emphasize that it is urinary supersaturation that must be


normalized, not simply the concentration of a particular reactant (such as
calcium). Supersaturation can be calculated from the 24-hour urine collection
when performed in an experienced laboratory. (See "Evaluation of the patient with
established nephrolithiasis and treatment if stone composition is unknown",
section on 24-hour urine collections).

Another component of monitoring is periodic ultrasonography to determine if new


stones have formed or previous stones have increased in size (show radiograph
1). Ultrasonography should be performed at one year and, if negative, every two
to four years thereafter.

CALCIUM OXALATE STONES – The following discussion primarily refers to the


prevention of calcium oxalate stones.

Dietary modification – From the viewpoint of diet, alterations in fluid, calcium,


protein, potassium, sucrose, and sodium intake may be beneficial [2]. (See "Risk
factors for idiopathic calcium stones-I"). The importance of a possible "stone clinic"
effect following dietary recommendations should not be underestimated. One
study found that 58 percent of 108 patients evaluated for kidney stones had, over
a five year period, no evidence of active stone disease after a visit to the stone
clinic in which minimal advice regarding diet and fluid intake was given [3]. Those
patients who were metabolically inactive showed an increase in urine volume at
follow-up versus no change in those who continued to form stones.

High fluid intake – Increasing fluid intake to above 2 liters per day, including
drinking at night (although it is not essential that the patient wake up several
times per night to urinate), will increase the urine flow rate and lower the urine
solute concentration, both of which might protect against stone formation. In one
prospective trial, 199 patients with a first calcium stone were randomly assigned
to no therapy or recommendation of a high fluid intake [4]. At five years, the
incidence of new stone formation was significantly lower in the treated patients
than in those in the control group (12 versus 27 percent). Furthermore, the stone
formers had a daily urine output at baseline that was 250 to 350 mL less than
controls.

Similar findings were noted in another prospective study [5]. Stone formers who
remained free of stones were noted to have a greater increase in urine volume
than those who had recurrent disease (320 mL/day versus no change).

The type of fluid taken also may be important:

• Grapefruit juice may enhance the risk of developing stones [6,7]. In the
Nurses' Health study, for example, one eight ounce (240 mL) serving per day
resulted in a 44 percent increase in the risk of stone formation [7].

• Higher tea and coffee consumption reduced the risk of stone formation by
approximately 10 percent per cup per day [6,7].

• Consuming one bottle of beer/day may reduce risk of stone development by


40 percent [8].

Reduced protein intake – Similar adverse changes in urinary calcium, uric


acid, and citrate excretion can be induced by a high protein diet, since the
metabolism of sulfur-containing amino acids increases the daily acid load by
generating sulfuric acid (show figure 1). Animal protein is much more likely to
induce this effect than vegetable protein, since it has a higher sulfur content and
therefore generates more acid [9]. (See "Risk factors for idiopathic calcium
stones-I", see section on Protein for a discussion of how acid loading produces
these changes).
Thus, lowering protein intake to about 1 g/kg per day will produce favorable
changes in the urine [2]. Although it has not been proven that this will reduce the
incidence of stone formation, a high animal protein diet is a risk factor for renal
stones in men [10], but not in women [11,12].

Increasing dietary fruits and vegetables may reduce the risk of calcium oxalate
stone formation, particularly in patients who self-select a diet that is low in fruits
and vegetables. This benefit is primarily the result of increasing citrate excretion
[13].

Limiting sodium intake – Calcium is reabsorbed passively in the proximal


tubule down the favorable concentration gradient created by the reabsorption of
sodium and water. (See "Diuretics and calcium balance", for a review of renal
calcium handling). Thus, a low sodium diet (to 80 to 100 meq/day) can enhance
proximal sodium and calcium reabsorption, leading to a reduction in calcium
excretion. In one study, for example, lowering sodium intake from 200 to 80
meq/day diminished calcium excretion by as much as 100 mg/day (2.5 mmol/day)
[14].

Calcium intake – Although hypercalciuria is a common problem in stone


formers, limiting calcium intake is not recommended. The decrease in free
intestinal calcium leads to overabsorption of dietary oxalate and enhanced oxalate
excretion, since less insoluble calcium oxalate is formed in the intestinal lumen.
The net effect may be increased supersaturation of the urine with respect to
calcium oxalate and an enhanced tendency to stone formation. (See "Risk factors
for idiopathic calcium stones-I", section on Dietary factors).

The ability to help prevent new stone formation with a normal calcium intake was
shown in part by a five year study that compared two diets among men with
idiopathic hypercalciuria and recurrent calcium oxalate stones [15]. In this trial,
120 such men were randomly assigned to either a diet consisting of a normal
amount of calcium (1200 mg/day [30 mmol/day]) and low amounts of animal
protein (52 g/day) and salt (2900 mg/day [50 mmol/day] of sodium chloride) or a
diet containing a low amount of calcium (400 mg/day [10 mmol/day]).

At five years, a significantly lower risk of stone recurrence was observed among
the group administered the normal-calcium, low animal-protein, low-salt diet
(unadjusted relative risk of 0.49 with a CI of 0.24 to 0.98). This selective benefit
likely arose because of a decrease in urinary oxalate excretion compared to an
increase with the low calcium diet; the urine calcium actually decreased in both
treatment arms. However, the independent effect of calcium is unclear given that
the amounts of animal protein and salt ingested among those in the low calcium
diet differed from that of patients in the normal calcium diet group.

In addition to increasing stone formation, a low calcium diet may have a second
deleterious effect in patients with idiopathic hypercalciuria: wasting of calcium
from the bone and the kidney and the development of negative calcium balance
[2,16]. This extra loss of calcium can exacerbate the already diminished bone
density in some of these patients, a complication that may be due to enhanced
bone resorption [16].

It should be noted that calcium supplements are less effective in preventing


recurrent stones than is a normal calcium diet and may even increase risk [17].
Some data suggest that it may be related to the timing of calcium intake. If the
supplements are taken with meals, this may be a time when dietary oxalate can
be bound to calcium rather than at bedtime when intestinal oxalate levels are
reduced and therefore unavailable for binding [18]. Despite this possibility, there
are insufficient data to support the use of supplements in typical stone formers, as
there may be some other unidentified factors in dairy products that is protective.

Drug therapy – Drug therapy is indicated if the stone disease remains active (as
evidenced by the formation of new stones, enlargement of old stones, or the
passage of gravel) despite attempted dietary modification over a three to six
month period. The aim of therapy is to prevent further calcium oxalate
precipitation; dissolution of already existing calcium stones is highly unlikely (in
comparison to uric acid or cysteine stones). Thus, passage of a stone does not
necessarily reflect a therapeutic failure in a patient known to have renal stones
prior to the institution of therapy.

Initial drug therapy varies with the metabolic abnormality that is present:

• Thiazide diuretics for hypercalciuria


• Allopurinol or potassium citrate for hyperuricosuria
• Potassium citrate for hypocitraturia
• Potassium citrate for type 1 renal tubular acidosis

Patient compliance may become an important issue over the long-term. The trials
documenting benefit from these interventions required at least three years before
the results were significant [1]. In an analysis of over 3000 patients followed in a
well organized clinic at the University of Chicago, the reduction in urinary
supersaturation remained constant or improved over time in those who adhered to
yearly follow-up [1]. However, only 15 to 40 percent of patients complied with the
follow-up requirements by three years. How well the noncompliers adhered to
long-term therapy is not known.

Hypercalciuria – Patients with idiopathic hypercalciuria (ie, not due to


hypercalcemia as with primary hyperparathyroidism or sarcoidosis) and persistent
active stone disease should be treated with a normal-calcium, low animal-protein,
and low-salt diet [15] plus a thiazide diuretic such as chlorthalidone (which has a
longer half-life) or hydrochlorothiazide.

Thiazide therapy can lower calcium excretion by as much as 150 mg/day (3.75
mmol/day), primarily by inducing mild volume depletion (leading to a
compensatory rise in the proximal reabsorption of sodium and therefore of
calcium) and, possibly by directly enhancing active calcium reabsorption in the
distal tubule [19]. (See "Diuretics and calcium balance"). The net effect may be a
90 percent reduction in the incidence of new stones (although there is also an
appreciable improvement of 50 to 65 percent in placebo treated patients) [20-22].
The full benefit may not be seen unless sodium intake is restricted [23].

The diuretic dose is generally started at 12.5 to 25 mg/day of chlorthalidone or


hydrochlorothiazide (or its equivalent) to minimize diuretic-induced complications,
but most patients will require 50 to 100 mg/day to achieve adequate lowering of
the urine calcium. In particular, hypokalemia should be avoided, since low
potassium levels reduce urinary citrate excretion (see "Hypocitraturia" below). A
low calcium diet should be avoided because it increases the risk of stone formation
(see "Calcium intake" above) [15].

The tendency toward positive calcium balance with a thiazide diuretic may have an
additional beneficial effect: increasing bone mineralization and decreasing the
incidence of hip fracture in older patients. (See "Drugs that affect bone
metabolism"). This will also be helpful in patients who have mistakenly been on a
low calcium and/or high sodium diet, both of which can lead to negative calcium
balance and osteopenia in patients with idiopathic hypercalciuria. (See "Risk
factors for idiopathic calcium stones-I", section on Hypercalciuria).

Urinary calcium and sodium excretion should be monitored after the institution of
thiazide therapy. If hypercalciuria persists, a high sodium intake may be
responsible and efforts should be made to reduce sodium excretion below 100
meq/day. The potassium-sparing diuretic amiloride (5 to 10 mg/day) can also be
added, since this drug directly increases calcium reabsorption in the cortical
collecting tubule, further lowering calcium excretion [24]. (See "Diuretics and
calcium balance", section on Cortical collecting tubule and amiloride).

There are two alternatives if hypercalciuria persists or the thiazide is not well
tolerated. One option is the administration of 60 to 80 meq alkali per day as
potassium bicarbonate or potassium citrate (citrate is rapidly metabolized to
bicarbonate) [25]. (Potassium supplements should not usually be given with
amiloride, since the combination can lead to potassium retention and
hyperkalemia.)

Via an unknown mechanism, raising the plasma bicarbonate concentration


increases calcium reabsorption and lowers calcium excretion [26,27]. For this to
occur, however, the potassium salt must be given; the volume expansion induced
by sodium bicarbonate or sodium citrate will increase sodium and therefore
calcium excretion, counteracting the effect of the elevation in the plasma
bicarbonate concentration [26-28]. The administration of potassium citrate or
potassium bicarbonate may have an additional beneficial effect by increasing the
urinary excretion of citrate, a potent inhibitor of calcium stone formation (see
below).

The second option is the administration of neutral phosphate (orthophosphate),


which both reduces the excretion of calcium and increases the excretion of
inhibitors of crystallization (such as pyrophosphate). (See "No metabolic
abnormality" below). However, there are no randomized trials documenting the
effectiveness of this strategy in preventing stone recurrence.

Hyperuricosuria – If dietary modification is ineffective, patients with


hyperuricosuria, in whom uric acid crystals can act as a nidus for calcium stone
formation, can be effectively treated with allopurinol (100 to 300 mg/day), if
dietary modification is ineffective [20,29]. New stone formation can be diminished
by 80 percent with allopurinol (versus only 60 percent with placebo) (show figure
2) [29]. Alkali therapy with potassium citrate (60 to 80 meq/day) also may be
beneficial, since raising the urine pH above 6.0 will convert insoluble uric acid to
the much more soluble urate salt [30], but there are no trials addressing this
intervention.

Hypocitraturia – Increasing urinary citrate excretion is the goal in patients with


hypocitraturia, since citrate inhibits stone formation by forming a poorly
dissociable but soluble complex with calcium. Citrate excretion can be enhanced by
alkalinizing the plasma by the daily administration of 30 to 80 meq of potassium
citrate or potassium bicarbonate [31-33]. In one controlled study, for example,
the incidence of new stone formation fell in hypocitraturic patients fell from 1.2 to
0.1 per patient year in the group treated with potassium citrate as opposed to no
change in the placebo group [31]. This benefit was associated with an
approximate doubling of citrate excretion.

In contrast to the beneficial effect of potassium citrate or potassium bicarbonate, a


nonalkalinizing salt such as potassium chloride does not increase citrate excretion
in normokalemic subjects [32], while using orange juice as a source of potassium
and citrate has some less desirable effects. Although orange juice produces as
great an increase in citrate excretion as potassium citrate, it does not lower
calcium excretion and it modestly raises oxalate excretion [33]. The presence of
calcium and oxalate in orange juice and the generation of oxalate from the
metabolism of ascorbic acid may be responsible for these findings.

By comparison, lemon juice may be an effective source of citrate among patients


with calcium nephrolithiasis and hypocitraturia. In one report, for example, the
ingestion of 4 ounces of lemon juice a day (mixed with tap water as lemonade for
a total volume of 2 liters) resulted in increased urinary citrate levels in 11 of 12
patients (average increase of 142 to 346 mg/day) who were either noncompliant
or intolerant of conventional citrate replacement therapy [34]. Active therapy also
resulted in decreased urinary calcium excretion and did not alter urinary oxalate
excretion. Further studies will be required before this dietary supplement can be
recommended to prevent stone recurrence.

Alkalinization raises citrate excretion by diminishing the uptake of filtered citrate


by the proximal tubular cells [35]. The mechanism by which this occurs is related
in part to the chemical form of citrate that is present in the lumen. Citrate can
exist at a physiologic pH either as a divalent or trivalent anion. Proximal citrate
reabsorption (via a sodium-citrate cotransporter in the luminal membrane)
preferentially occurs as the divalent anion. Raising the pH in the tubular lumen
converts the divalent form into the less reabsorbable trivalent form [30]:

Citrate(2-) + HCO3- –> Citrate(3-) + CO2 + H2O

Increasing the systemic pH may enhance citrate excretion by a second


mechanism. The associated intracellular alkalosis will diminish citrate metabolism
within the cells. The ensuing elevation in the cell citrate concentration will create a
less favorable concentration gradient for passive citrate movement from the
tubular lumen into the cell [33].

The net effect is decreased citrate uptake and increased citrate excretion. In
addition to the effect on pH, some of the administered citrate may be excreted
directly before being metabolized to bicarbonate [36]. Thus, potassium citrate has
a slightly greater citraturic effect than potassium bicarbonate [32,36].

On the other hand, metabolic acidosis diminishes citrate excretion due to


enhanced citrate reabsorption [35]. This effect is mediated both by conversion of
citrate(3-) to the more reabsorbable citrate(2-) and by increased citrate
metabolism (due to upregulation of the enzyme ATP citrate lyase) within the cells
[37]. Hypocitraturia probably contributes to the stone formation that is relatively
common in patients with untreated type 1 renal tubular acidosis (see
"Nephrolithiasis in renal tubular acidosis").

Hypokalemia, as may be produced by a thiazide diuretic for example, has a similar


stimulatory effect on citrate reabsorption. Potassium moves out of the cells to
repair the extracellular deficit and electroneutrality is maintained in part by the
movement of extracellular hydrogen into the cells. The intracellular acidosis will
enhance citrate metabolism, thereby lowering the cell citrate concentration and
creating a more favorable gradient for citrate reabsorption [36,38]. It is therefore
desirable to correct hypokalemia in recurrent stone formers.

Enteric hyperoxaluria – Treatment in enteric hyperoxaluria (see "Risk factors


for idiopathic calcium stones-I") is directed toward diminishing intestinal oxalate
absorption [20,39]. The initial regimen consists of a high fluid intake, potassium
citrate to correct metabolic acidosis if present, and oral calcium carbonate (1 to 4
g/day) to bind oxalate in the intestinal lumen. Although some of the calcium is
absorbed, there is a proportionately greater fall in oxalate excretion.

A low-fat, low-oxalate diet (show table 1) is another modality that may be helpful
in this disorder by reducing the quantity of fatty acids and free oxalate in the
colon. This diet, however, is often nutritionally inadequate in these patients who
have malabsorption and/or a short bowel syndrome. Cholestyramine, which binds
both bile acids and oxalate, can also be used, but side effects may be limiting.

No metabolic abnormality – A minority of patients with recurrent calcium


stones have no identifiable metabolic abnormality [20,40]. Careful analysis has
shown that these patients frequently have more calcium and less citrate in the
urine than normals, although neither value is clearly abnormal. Discriminant
analysis suggests that citrate excretion in stone formers tends to be less than 4.4
times calcium excretion (mg/mg) in men and less than 3.7 times calcium excretion
in women [40].

Stone formers also tend to have a lower urine volume, another factor that could
promote stone formation. In one report, for example, patients with a first stone
had a baseline daily urine output that was 250 to 350 mL less than controls [4].

This emphasizes the importance of considering the concentrations of urinary


factors and not simply the absolute amount of excretion. As an example, even if
the urine calcium is not in the traditionally accepted hypercalciuric range, the urine
calcium concentration will be high when the urine volume is low. If the urine
volume cannot be consistently maintained at a higher level, the urine calcium
must therefore be reduced to lower the calcium concentration .

There is some suggestive evidence that lowering calcium excretion with a thiazide
diuretic may be beneficial, even in patients who are not hypercalciuric [21,22].
The possible effect of potassium citrate in this setting remains to be determined.

Summary and recommendations – From the viewpoint of diet, alterations in


fluid, calcium, protein, and sodium intake may be beneficial. We therefore
recommend the following:

• Increasing fluid intake to above 2 liters per day, including drinking at night
(although it is not essential that the patient wake up several times per night to
urinate), will increase the urine flow rate and lower the urine solute concentration,
both of which may protect against stone formation.

To reach this goal, the best strategy is to recommend how much additional fluid
the patient should drink based on his or her 24 hour urine volume. As an example,
if the total urine volume is 1.5 liters, then we recommend two additional 8 ounce
(240 mL) glasses of fluid each day to reach the goal of at least 2 liters of urine
output per day.

• Although it has not been proven that a low protein diet will reduce the
incidence of stone formation, a high animal protein diet is a risk factor for renal
stones in men [10], but not in women [11,12].

• A low sodium diet (to 80 to 100 meq/day) can enhance proximal sodium and
calcium reabsorption, leading to a reduction in calcium excretion.

• Increasing dietary potassium intake is encouraged, as this substantially


decreases risk in men and older women.

• Limiting dietary calcium intake is not recommended, even though


hypercalciuria is a common problem in stone formers. (See "Calcium intake"
above).

Drug therapy is indicated if the stone disease remains active (as evidenced by the
formation of new stones, enlargement of old stones, or the passage of gravel) or
adequate improvements are not realized in urinary chemistries despite attempted
dietary modification over a three to six month period.

Initial drug therapy varies with the metabolic abnormality that is present:

• Thiazide diuretics for hypercalciuria


• Allopurinol or potassium citrate for hyperuricosuria
• Potassium citrate for hypocitraturia
• Potassium citrate for type 1 renal tubular acidosis

In general, the response to dietary or drug therapy is monitored by repeat 24-hour


urine collections as performed in the initial evaluation of the patient with
established stone disease. We routinely obtain one 24-hour urine collection at four
to six weeks after therapy has begun.

CALCIUM PHOSPHATE STONES – In general, patients with calcium phosphate


stones have the same risk factors as those with calcium oxalate stones (except for
hyperoxaluria and hyperuricosuria); as a result, therapy for recurrent stone
formation is probably similar in most cases [41]. However, some calcium
phosphate stone formers have a persistently elevated urine pH (usually above 6.0)
due to overt or incomplete type 1 renal tubular acidosis. Although the
administration of potassium citrate in this setting may diminish the frequency of
stone growth or new formation, it could also make it worse by raising the urine
pH, thereby increasing the likelihood of calcium phosphate crystal formation and
thus needs to be used with caution. (See "Nephrolithiasis in renal tubular
acidosis").

STONE COMPOSITION NOT KNOWN – In some patients, the stone composition


remains unknown. The management of such patients is discussed elsewhere. (See
"Evaluation of the patient with established nephrolithiasis and treatment if stone
composition is unknown").

References
1. Parks, JH, Asplin, JR, Coe, FL. Patient adherence to long-term medical
treatment of kidney stones. J Urol 2001; 166:2057.
2. Parivar, F, Low, RK, Stoller, ML. Influence of diet on urinary stone disease. J
Urol 1996; 155:432.
3. Hosking, DH, Erickson, SB, Vanden Berg, CJ, et al. The stone clinic effect in
patients with idiopathic calcium urolithiasis. J Urol 1983; 130:1115.
4. Borghi, L, Meschi, T, Amato, F, et al. Urinary volume, water and recurrences in
idiopathic calcium nephrolithiasis: A 5-year randomized prospective study. J Urol
1996; 155:839.
5. Strauss, AL, Coe, FL, Deutsch, L, Parks, JH. Factors that predict relapse of
calcium nephrolithiasis during treatment: A prospective study. Am J Med 1982;
72:17.
6. Curhan, GC, Willett, WC, Rimm, EB, et al. Prospective study of beverage use
and the risk of kidney stones. Am J Epidemiol 1996; 143:240.
7. Curhan, GC, Willett, WC, Speizer, FE, Stampfer, MJ. Beverage use and risk for
kidney stones in women. Ann Intern Med 1998; 128:534.
8. Hirvonen, T, Pietinen, P, Virtanen, M, et al. Nutrient intake and use of
beverages and the risk of kidney stones among male smokers. Am J Epidemiol
1999; 150:187.
9. Breslau, NA, Brinkley, L, Hill, KD, Pak, CY. Relationship of animal protein-rich
diet to kidney stone formation and calcium metabolism. J Clin Endocrinol Metab
1988; 66:140.
10. Curhan, GC, Willett, WC, Rimm, EB, Stampfer, MJ. A prospective study of
dietary calcium and other nutrients and the risk of symptomatic kidney stones. N
Engl J Med 1993; 328:833.
11. Curhan, GC, Willett, WC, Knight, EL, Stampfer MJ Dietary factors and the risk
of incident kidney stones in younger women: Nurses' Health Study II. Arch Intern
Med 2004; 164:885.
12. Curhan, GC, Willett, WC, Speizer, FE, et al. Comparison of dietary calcium with
supplemental calcium and other nutrients as factors affecting the risk for kidney
stones in women. Ann Intern Med 1997; 126:497.
13. Meschi, T, Maggiore, U, Fiaccadori, E, et al. The effect of fruits and vegetables
on urinary stone risk factors. Kidney Int 2004; 66:2402.
14. Muldowney, FP, Freaney, R, Moloney, MF. Importance of dietary sodium in the
hypercalciuria syndrome. Kidney Int 1982; 22:292.
15. Borghi, L, Schianchi, T, Meschi, T, Guerra, A. Comparison of two diets for the
prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med 2002;
346:77.
16. Bataille, P, Achard, JM, Fournier, A, et al. Diet, vitamin D and vertebral mineral
density in hypercalciuric calcium stone formers. Kidney Int 1991; 39:1193.
17. Curhan, GC, Willett, WC, Speizer, FE, et al. Comparison of dietary calcium with
supplemental calcium and other nutrients as factors affecting the risk for kidney
stones in women. Ann Intern Med 1997; 126:497.
18. Domrongkitchaiporn, S, Sopassathit, W, Stitchantrakul, W, et al. Schedule of
taking calcium supplement and the risk of nephrolithiasis. Kidney Int 2004;
65:1835.
19. Nijenhuis, T, Hoenderop, JG, Loffing, J, Van Der, Kemp AW. Thiazide-induced
hypocalciuria is accompanied by a decreased expression of Ca2+ transport
proteins in kidney. Kidney Int 2003; 64:555.
20. Coe, FL, Parks, JH, Asplin, JR. The pathogenesis and treatment of kidney
stones. N Engl J Med 1992; 327:1141.
21. Ettinger, B, Citrov, JT, Livermore, B, Dolman, LI. Chlorthalidone reduces
calcium oxalate calculus recurrence but magnesium hydroxide does not. J Urol
1988; 139:679.
22. Laerum, E, Larsen, S. Thiazide prophylaxis of urolithiasis. A double-blind study
in general practice. Acta Med Scand 1984; 215:383.
23. Nijenhuis, T, Hoenderop, JG, Loffing, J, Van Der, Kemp AW. Thiazide-induced
hypocalciuria is accompanied by a decreased expression of Ca2+ transport
proteins in kidney. Kidney Int 2003; 64:555.
24. Alon, U, Costanzo, LS, Chan, JC. Additive hypocalciuric effects of amiloride and
hydrochlorothiazide in patients treated with calcitriol. Miner Electrolyte Metab
1984; 10:379.
25. Pak, CY, Peterson, R, Sakhaee, K, et al. Correction of hypocitraturia and
prevention of stone formation by combined thiazide and potassium citrate therapy
in thiazide-unresponsive hypercalciuric nephrolithiasis. Am J Med 1985; 79:284.
26. Lemann, J Jr, Gray, RW, Pleuss, JA. Potassium bicarbonate, but not sodium
bicarbonate, reduces urinary calcium excretion and improves calcium balance in
healthy men. Kidney Int 1989; 35:688.
27. Sakhaee, K, Nicar, M, Hill, K, Pak, CY. Contrasting effects of potassium citrate
and sodium citrate therapies on urinary chemistries and crystallization of stone-
forming salts. Kidney Int 1983; 24:348.
28. Preminger, GM, Sakhaee, K, Pak, CY. Alkali action on the urinary crystallization
of calcium salts: Contrasting responses to sodium citrate and potassium citrate. J
Urol 1988; 139:240.
29. Ettinger, B, Tang, A, Citron, JT, et al. Randomized trial of allopurinol in the
prevention of calcium oxalate calculi. N Engl J Med 1986; 315:1386.
30. Pak, CY, Peterson, R. Successful treatment of hyperuricosuric calcium oxalate
nephrolithiasis with potassium citrate. Arch Intern Med 1986; 146:863.
31. Barcelo, P, Wuhl, O, Servitge, E, et al. Randomized double-blind study of
potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J Urol 1993;
150:1761.
32. Sakhaee, K, Alpern, R, Jacobson, HR, Pak, CY. Contrasting effects of varying
potassium salts on renal citrate excretion. J Clin Endocrinol Metab 1991; 72:396.
33. Wabner, CL, Pak, CY. Effect of orange juice consumption on urinary stone risk
factors. J Urol 1993; 149:1405.
34. Seltzer, MA, Low RK, McDonald, M, et al. Dietary manipulation with lemonade
to treat hypocitraturic calcium nephrolithiasis. J Urol 1996; 156:907.
35. Hamm, LL. Renal handling of citrate. Kidney Int 1990; 38:728.
36. Sakhaee, K, Alpern, R, Poindexter, J, Pak, CY. Citraturic response to oral citric
acid load. J Urol 1992; 147:975.
37. Melnick, JZ, Srere, PA, Eishourbagy, NA, et al. Adenosine triphosphate citrate
lyase mediates hypocitraturia in rats. J Clin Invest 1996; 98:2381.
38. Levi, M, McDonald, LA, Preisig, PA, Alpern, RJ. Chronic K depletion stimulates
rat renal brush-border membrane Na-citrate cotransporter. Am J Physiol 1991;
261:F767.
39. Williams, HE. Oxalic acid and the hyperoxaluric syndromes. Kidney Int 1978;
13:410.
40. Parks, JH, Coe, FL. A urinary calcium-citrate index for the evaluation of
nephrolithiasis. Kidney Int 1986; 30:85.
41. Gault, MH, Chafe, LL, Morgan, JM, et al. Comparison of patients with idiopathic
calcium phosphate and calcium oxalate stones. Medicine (Baltimore) 1991; 70:345.

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