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Role of proximal tubules in the pathogenesis of kidney disease.
[cystinuria]
The
proximal
tubules
make
up
a
significant
portion
of
the
kidneys
;
proximal
tubule
epithelial
cells
are
the
most
populous
cell
type
in
the
kidney
,
and
carry
out
diverse
regulatory
and
endocrine
functions
where
numerous
transporters
are
located
.
Under
normal
circumstances
,
more
than
two
thirds
of
filtered
salt
and
water
,
and
all
filtered
bicarbonate
is
reabsorbed
in
the
proximal
tubule
.
A
number
of
inherited
and
acquired
acid-base
and
tubule
disorders
are
linked
to
impaired
transporters
in
the
proximal
tubule
cells
.
Equally
important
is
the
intrinsic
immune
characteristics
of
proximal
tubule
cells
that
give
them
the
ability
to
also
function
as
immune
responders
to
a
wide
range
of
immunologic
,
ischemic
or
toxic
injury
.
It
is
therefore
not
surprising
that
proximal
tubule-related
phenomena
are
closely
related
to
the
pathogenesis
of
a
vast
array
of
kidney
diseases
.
Many
kidney
diseases
,
acute
and
chronic
,
first
manifest
with
proximal
tubule
disorders
.
Recent
insight
into
molecular
characteristics
of
transport
functions
in
the
proximal
tubules
,
and
the
recognition
that
proximal
tubule
cells
possess
intrinsic
immune
responses
have
contributed
to
an
improved
understanding
of
important
areas
in
nephrology
,
such
as
Fanconi
's
syndrome
,
renal
tubular
acidosis
,
phosphate
wasting
syndromes
,
Dent
's
disease
,
cystinuria
and
other
amino
acid
transport
disorders
,
acute
kidney
injury
,
and
the
role
of
proximal
tubules
in
progressive
kidney
disease
.
Megalin
/
cubilin-mediated
endocytosis
by
proximal
tubule
cells
of
increased
quantities
of
filtered
proteins
(
protein
overloading
)
in
glomerular
diseases
appears
to
evoke
cell
stress
responses
resulting
in
increased
inflammatory
cytokines
leading
to
tubulointerstitial
inflammation
and
fibrosis
.
Finally
,
the
proximal
tubule
may
be
the
site
of
both
active
vitamin
D
synthesis
through
the
action
of
1
-
α-hydroxylase
,
and
the
site
where
erythropoietin
synthesis
takes
place
.
Thus
,
proximal
tubule
injury
also
contributes
to
two
distressing
consequences
of
chronic
kidney
disease
:
mineral-
bone
disorder
and
anemia
.
Diseases
Validation
Diseases presenting
"and the role of proximal tubules in progressive kidney disease"
symptom
cystinuria
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