Clinical Journal of the American Society of Nephrology,
Journal Year:
2016,
Volume and Issue:
11(9), P. 1664 - 1674
Published: April 12, 2016
Glomerular
diseases
are
common
and
important.
They
can
arise
from
systemic
inflammatory
or
metabolic
that
affect
the
kidney.
Alternately,
they
caused
primarily
by
local
glomerular
abnormalities,
including
genetic
diseases.
Both
intrinsic
cells
leukocytes
critical
to
healthy
glomerulus
dysregulation
in
disease.
Mesangial
cells,
endothelial
podocytes,
parietal
epithelial
within
all
play
unique
specialized
roles.
Although
a
specific
disease
often
affects
particular
cell
type,
close
proximity,
interdependent
functions
interactions
between
mean
even
affecting
one
type
usually
indirectly
influence
others.
In
addition
those
glomerulus,
patrol
health
mediate
injury
Distinct
leukocyte
types
subsets
present,
with
some
being
involved
different
ways
an
individual
Cells
of
innate
adaptive
immune
systems
important,
directing
responses,
locally
mediating
injury,
potentially
dampening
inflammation
facilitating
repair.
The
advent
new
molecular
techniques,
models
means
we
better
understand
both
basic
biology
pathogenesis
This
understanding
should
lead
diagnostic
biomarkers,
predictors
prognosis,
severity,
relapse.
With
this
knowledge
comes
promise
therapies
future,
directed
toward
halting
pathways
fibrosis,
interrupting
underlying
pathophysiology
significant
progressive
Kidney International,
Journal Year:
2016,
Volume and Issue:
89(6), P. 1221 - 1230
Published: March 19, 2016
Podocytes
maintain
the
glomerular
filtration
barrier,
and
stability
of
this
barrier
depends
on
their
highly
differentiated
postmitotic
phenotype,
which
also
defines
particular
vulnerability
glomerulus.
Recent
podocyte
biology
gene
disruption
studies
in
vivo
indicate
a
causal
relationship
between
abnormalities
single
molecules
proteinuria
glomerulosclerosis.
live
under
various
stresses
pathological
stimuli.
They
adapt
to
homeostasis,
but
excessive
stress
leads
maladaptation
with
complex
biological
changes
including
loss
integrity
dysregulation
cellular
metabolism.
Podocyte
injury
causes
detachment
from
basement
membrane.
In
addition
"sick"
podocytes
detachment,
our
understanding
responses
following
needs
address
pathways
sclerosis.
Studies
have
found
variety
dysfunction
vivo,
such
as
podocyte-endothelial
cross
talk
activation
podocyte-parietal
cell
interactions,
all
help
us
understand
scenario
its
consequences.
This
review
focuses
aspects
adaptive
or
maladaptive
that
lead
major
consequence,
Clinical Journal of the American Society of Nephrology,
Journal Year:
2017,
Volume and Issue:
12(3), P. 502 - 517
Published: Feb. 27, 2017
Focal
segmental
glomerulosclerosis
(FSGS)
is
a
leading
cause
of
kidney
disease
worldwide.
The
presumed
etiology
primary
FSGS
plasma
factor
with
responsiveness
to
immunosuppressive
therapy
and
risk
recurrence
after
transplant-important
characteristics.
In
contrast,
adaptive
associated
excessive
nephron
workload
due
increased
body
size,
reduced
capacity,
or
single
glomerular
hyperfiltration
certain
diseases.
Additional
etiologies
are
now
recognized
as
drivers
FSGS:
high-penetrance
genetic
mutations
in
one
nearly
40
genes,
virus-associated
FSGS,
medication-associated
FSGS.
Emerging
data
support
the
identification
sixth
category:
APOL1
allele-associated
individuals
sub-Saharan
ancestry.
classification
particular
patient
relies
on
integration
findings
from
clinical
history,
laboratory
testing,
biopsy,
some
patients,
testing.
biopsy
can
be
helpful,
clues
provided
by
features
light
microscopy
(
International Journal of Molecular Sciences,
Journal Year:
2019,
Volume and Issue:
20(15), P. 3683 - 3683
Published: July 27, 2019
As
a
major
component
of
cell
membrane
lipids,
Arachidonic
acid
(AA),
being
the
lipid
content,
is
mainly
metabolized
by
three
kinds
enzymes:
cyclooxygenase
(COX),
lipoxygenase
(LOX),
and
cytochrome
P450
(CYP450)
enzymes.
Based
on
these
metabolic
pathways,
AA
could
be
converted
into
various
metabolites
that
trigger
different
inflammatory
responses.
In
kidney,
prostaglandins
(PG),
thromboxane
(Tx),
leukotrienes
(LTs)
hydroxyeicosatetraenoic
acids
(HETEs)
are
generated
from
AA.
An
increased
level
(PGs),
TxA2
leukotriene
B4
(LTB4)
results
in
damage
to
kidney.
Moreover,
LTB4-leukotriene
receptor
1
(BLT1)
axis
participates
acute
kidney
injury
via
mediating
recruitment
renal
neutrophils.
addition,
can
regulate
ion
transport
through
19-hydroxystilbenetetraenoic
(19-HETE)
20-HETE,
both
which
produced
monooxygenase.
Epoxyeicosatrienoic
(EETs)
CYP450
enzyme
also
plays
paramount
role
during
inflammation
process.
For
example,
14
15-EET
mitigated
ischemia/reperfusion-caused
tubular
epithelial
damage.
Many
drug
candidates
target
metabolism
pathways
developed
treat
inflammation.
These
observations
support
an
extraordinary
interest
wide
range
studies
interventions
aiming
control
The Journal of Cell Biology,
Journal Year:
2015,
Volume and Issue:
209(2), P. 199 - 210
Published: April 27, 2015
The
function
of
the
kidney,
filtering
blood
and
concentrating
metabolic
waste
into
urine,
takes
place
in
an
intricate
functionally
elegant
structure
called
renal
glomerulus.
Normal
glomerular
retains
circulating
cells
valuable
macromolecular
components
plasma
blood,
resulting
urine
with
just
trace
amounts
proteins.
Endothelial
capillaries,
podocytes
wrapped
around
them,
fused
extracellular
matrix
these
form
altogether
comprise
filtration
barrier,
a
dynamic
highly
selective
filter
that
sieves
on
basis
molecular
size
electrical
charge.
Current
understanding
structural
organization
cellular
draws
from
studies
human
diseases
animal
models
dysfunction.
Journal of the American Society of Nephrology,
Journal Year:
2018,
Volume and Issue:
29(3), P. 759 - 774
Published: Jan. 10, 2018
FSGS
describes
a
renal
histologic
lesion
with
diverse
causes
and
pathogenicities
that
are
linked
by
podocyte
injury
depletion.
Subclasses
of
include
primary,
genetic,
secondary
forms,
the
latter
comprising
maladaptive,
viral,
drug-induced
FSGS.
Despite
sharing
certain
clinical
features,
these
subclasses
differ
noticeably
in
management
prognosis.
Without
an
accepted
nongenetic
biomarker
discriminates
among
types,
classification
patients
is
often
challenging.
This
review
summarizes
including
onset
severity
proteinuria
as
well
presence
nephrotic
syndrome,
may
aid
identifying
specific
subtype.
The
characterized
segmental
sclerosis
must
be
differentiated
from
nonspecific
focal
global
glomerulosclerosis.
No
light
microscopic
features
pathognomonic
for
particular
subcategory.
characteristics
foot
process
effacement
on
electron
microscopy,
while
helpful
discriminating
between
primary
maladaptive
FSGS,
little
utility
detecting
genetic
forms
When
cannot
classified
clinicopathologic
assessment,
analysis
should
offered.
Next
generation
DNA
sequencing
enables
cost-effective
screening
multiple
genes
simultaneously,
but
determining
pathogenicity
detected
variant
A
more
systematic
evaluation
patients,
suggested
herein,
will
likely
improve
therapeutic
outcomes
design
future
trials
Journal of Clinical Investigation,
Journal Year:
2023,
Volume and Issue:
133(4)
Published: Feb. 14, 2023
Kidney
disease
is
a
major
driver
of
mortality
among
patients
with
diabetes
and
diabetic
kidney
(DKD)
responsible
for
close
to
half
all
chronic
cases.
DKD
usually
develops
in
genetically
susceptible
individual
as
result
poor
metabolic
(glycemic)
control.
Molecular
genetic
studies
indicate
the
key
role
podocytes
endothelial
cells
driving
albuminuria
early
diabetes.
Proximal
tubule
changes
show
strong
association
glomerular
filtration
rate.
Hyperglycemia
represents
cellular
stress
by
altering
metabolism
imposing
an
excess
workload
requiring
energy
oxygen
proximal
cells.
Changes
induce
adaptive
hypertrophy
reorganization
actin
cytoskeleton.
Later,
mitochondrial
defects
contribute
increased
oxidative
activation
inflammatory
pathways,
causing
progressive
function
decline
fibrosis.
Blockade
renin-angiotensin
system
or
sodium-glucose
cotransporter
associated
protection
slowing
decline.
Newly
identified
molecular
pathways
could
provide
basis
development
much-needed
novel
therapeutics.
