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Potential pharmacologic treatments for cystinuria and for calcium stones associated with hyperuricosuria.
[cystinuria]
Two
new
potential
pharmacologic
therapies
for
recurrent
stone
disease
are
described
.
The
role
of
hyperuricosuria
in
promoting
calcium
stones
is
controversial
with
only
some
but
not
all
epidemiologic
studies
demonstrating
associations
between
increasing
urinary
uric
acid
excretion
and
calcium
stone
disease
.
The
relationship
is
supported
by
the
ability
of
uric
acid
to
"
salt
out
"
(
or
reduce
the
solubility
of
)
calcium
oxalate
in
vitro
.
A
randomized
,
controlled
trial
of
allopurinol
in
patients
with
hyperuricosuria
and
normocalciuria
was
also
effective
in
preventing
recurrent
stones
.
Febuxostat
,
a
nonpurine
inhibitor
of
xanthine
oxidase
(
also
known
as
xanthine
dehydrogenase
or
xanthine
oxidoreductase
)
may
have
advantages
over
allopurinol
and
is
being
tested
in
a
similar
protocol
,
with
the
eventual
goal
of
determining
whether
urate-lowering
therapy
prevents
recurrent
calcium
stones
.
Treatments
for
cystinuria
have
advanced
little
in
the
past
30
years
.
Atomic
force
microscopy
has
been
used
recently
to
demonstrate
that
effective
inhibition
of
cystine
crystal
growth
is
accomplished
at
low
concentrations
of
l-cystine
methyl
ester
and
l-cystine
dimethyl
ester
,
structural
analogs
of
cystine
that
provide
steric
inhibition
of
crystal
growth
.
In
vitro
,
l-cystine
dimethyl
ester
had
a
significant
inhibitory
effect
on
crystal
growth
.
The
drug
's
safety
and
effectiveness
will
be
tested
in
an
Slc
3
a
1
knockout
mouse
that
serves
as
an
animal
model
of
cystinuria
.