Burton D Rose, MD
Gary Curhan, MD, ScD
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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").
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.
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).
• 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].
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].
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].
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:
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.
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 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.)
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].
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.
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].
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.
• 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.
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:
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