Nephrotic Syndrome: From Pathophysiology to Novel Therapeutic Approaches
Biomedicines,
Год журнала:
2024,
Номер
12(3), С. 569 - 569
Опубликована: Март 3, 2024
Nephrotic
edema
stands
out
as
one
of
the
most
common
complications
nephrotic
syndrome.
The
effective
management
hypervolemia
is
paramount
in
addressing
this
condition.
Initially,
"the
underfill
hypothesis"
suggested
that
proteinuria
and
hypoalbuminemia
led
to
fluid
extravasation
into
interstitial
space,
causing
intravascular
hypovolemia
activation
neurohormonal
compensatory
mechanisms,
which
increased
retention
salt
water.
Consequently,
recommended
involved
diuretics
human-albumin
infusion.
However,
recent
findings
from
human
animal
studies
have
unveiled
a
kidney-limited
sodium-reabsorption
mechanism,
attributed
presence
various
serine
proteases
tubular
lumen-activating
ENaC
channels,
thereby
sodium
reabsorption.
There
currently
no
standardized
guideline
for
diuretic
therapy.
In
clinical
practice,
loop
continue
be
preferred
initial
choice.
It
noteworthy
patients
often
exhibit
resistance
due
factors
such
high-sodium
diets,
poor
drug
compliance,
changes
pharmacokinetics
or
pharmacodynamics,
kidney
dysfunction,
decreased
renal
flow,
nephron
remodeling
proteasuria.
Considering
these
challenges,
combining
may
rational
approach
overcoming
resistance.
Despite
limited
data
available
on
treatment
syndrome
complicated
by
hypervolemia,
blockers
emerge
potential
add-on
edema.
Язык: Английский
Renal upregulation of NCC counteracts empagliflozin-mediated NHE3 inhibition in normotensive but not in hypertensive male rat
AJP Cell Physiology,
Год журнала:
2024,
Номер
326(6), С. C1573 - C1589
Опубликована: Апрель 1, 2024
This
study
suggests
that
reduced
NHE3-mediated
sodium
reabsorption
in
the
renal
proximal
tubule
may
account,
at
least
part,
for
BP-lowering
effect
of
SGLT2
inhibitors
setting
hypertension.
It
also
demonstrates
chronic
treatment
with
upregulates
NCC
activity,
phosphorylation,
and
expression
distal
normotensive
but
not
hypertensive
rats.
inhibitor-mediated
upregulation
seems
crucial
to
counteract
natriuresis
subjects
normal
BP.
Язык: Английский
Sodium Glucose Cotransporter-2 Inhibitors in Non-Diabetic Kidney Disease: Evidence in Experimental Models
Pharmaceuticals,
Год журнала:
2024,
Номер
17(3), С. 362 - 362
Опубликована: Март 11, 2024
Sodium
glucose
cotransporter
2
(SGLT2)
inhibitors
are
a
class
of
glucose-lowering
agents
widely
used
for
the
treatment
type
diabetes
mellitus.
A
number
clinical
trials
in
diabetic
patients
with
different
degrees
renal
impairment
have
clearly
demonstrated
that
SGLT2
reduce
progression
rate
kidney
disease.
Furthermore,
recent
studies
shown
also
exert
protective
effect
case
non-diabetic
Consequently,
it
has
been
hypothesized
nephroprotective
activity
these
drugs
could
exceed
canonical
impact
on
glycemic
control
and
resulting
beneficial
effects
be
consequence
their
pleiotropic
properties
(proven
reduction
inflammation,
fibrosis,
oxidative
stress
sympathetic
nervous
activity)
both
at
systemic
tissue
levels,
suggesting
efficacy
extended
to
nephropathies.
This
review
focuses
experimental
models
The
glucose-independent
mechanisms
potentially
implemented
by
ultimately
protect
described
detail,
conflicting
results,
when
present,
discussed.
Язык: Английский
Water and sodium conservation response induced by SGLT2 inhibitor ipragliflozin in Dahl salt-sensitive hypertensive rats
Hypertension Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 19, 2024
Язык: Английский
Oxidative Stress in Kidney Injury and Hypertension
Antioxidants,
Год журнала:
2024,
Номер
13(12), С. 1454 - 1454
Опубликована: Ноя. 27, 2024
Hypertension
(HTN)
is
a
major
contributor
to
kidney
damage,
leading
conditions
such
as
nephrosclerosis
and
hypertensive
nephropathy,
significant
causes
of
chronic
disease
(CKD)
end-stage
renal
(ESRD).
HTN
also
risk
factor
for
stroke
coronary
heart
disease.
Oxidative
stress,
inflammation,
activation
the
renin–angiotensin–aldosterone
system
(RAAS)
play
critical
roles
in
causing
injury
HTN.
Genetic
environmental
factors
influence
susceptibility
with
African
American
populations
having
higher
tendency
due
genetic
variants.
Managing
blood
pressure
(BP)
effectively
treatments
targeting
RAAS
activation,
oxidative
inflammation
crucial
preventing
damage
progression
HTN-related
CKD
ESRD.
Interactions
between
impacting
function
abnormalities
are
central
development.
Animal
studies
indicate
that
significantly
BP
regulation.
Anti-natriuretic
mechanisms
can
reset
pressure–natriuresis
relationship,
requiring
excrete
sodium
matched
intake.
Activation
intrarenal
angiotensin
II
receptors
contributes
retention
high
BP.
In
HTN,
gut
microbiome
affect
by
influencing
energy
metabolism
inflammatory
pathways.
models,
spontaneously
rat
infusion
model,
mirror
human
essential
hypertension
highlight
significance
pathogenesis.
Overproduction
reactive
oxygen
species
(ROS)
plays
role
development
Targeting
specific
NADPH
oxidase
(NOX)
isoforms
inhibit
ROS
production
enhance
antioxidant
may
improve
structure
while
lowering
pressure.
Therapies
like
SGLT2
inhibitors
mineralocorticoid
receptor
antagonists
have
shown
promise
reducing
activity,
offering
antihypertensive
protection
managing
CKD.
This
review
emphasizes
NOX
focusing
on
its
impact
Effective
management
Язык: Английский
SGLT2 inhibitors for alleviating heart failure through non-hypoglycemic mechanisms
Frontiers in Cardiovascular Medicine,
Год журнала:
2024,
Номер
11
Опубликована: Дек. 9, 2024
Sodium-glucose
cotransporter-2
(SGLT2)
inhibitors
afford
significant
cardiovascular
benefits
to
patients
with
diabetes
mellitus
and
heart
failure.
Three
large
randomized
clinical
trials
(EMPAREG-Outcomes,
DECLARE-TIMI58,
DAPA-HF)
have
shown
that
SGLT2
prevent
events
reduce
the
risk
of
death
hospital
admission
resulting
from
Patients
without
type
2
(T2DM)
also
experience
a
similar
degree
benefit
as
those
T2DM
do.
could
improve
cardiac
function
through
potential
non-hypoglycemic
mechanisms,
including
reduction
circulatory
volume
load,
regulation
energy
metabolism,
maintenance
ion
homeostasis,
alleviation
inflammation
oxidative
stress,
direct
inhibition
SGLT1
receptors
antimyocardial
fibrosis.
This
article
reviews
mechanism
which
prevent/alleviate
failure
pathways,
support
their
use
for
treatment
in
non-T2DM
patients.
Язык: Английский
Gliflozins in the Treatment of Non-diabetic Experimental Cardiovascular Diseases
Physiological Research,
Год журнала:
2024,
Номер
Suppl 1, С. S377 - S387
Опубликована: Авг. 22, 2024
A
new
class
of
antidiabetic
drugs
-
gliflozins
(inhibitors
sodium
glucose
cotransporter-2;
SGLT-2i)
stimulate
and
excretion,
thereby
contributing
to
improved
glycemic
control,
weight
loss
blood
pressure
reduction
in
diabetic
patients.
Large
clinical
trials
patients
with
type
2
diabetes
treated
empagliflozin,
canagliflozin
or
dapagliflozin
have
demonstrated
their
excellent
efficacy
improving
many
cardiovascular
outcomes,
including
the
death
from
diseases,
non-fatal
myocardial
infarction
stroke,
hospitalization
for
heart
failure.
Moreover,
beneficial
effects
SGLT-2i
were
also
decrease
proteinuria,
which
leads
a
lower
risk
progression
end-stage
renal
disease
thus
delay
initiation
replacement
therapy.
Unexpectedly,
cardioprotective
renoprotective
been
not
only
but
those
without
diabetes.
Recently,
much
effort
has
focused
on
failure
(either
reduced
preserved
ejection
fraction)
liver
disease.
Experimental
studies
highlighted
pleiotropic
SGLT-2
inhibitors
beyond
natriuretic
glycosuric
effects,
fibrosis,
inflammation,
reactive
oxygen
species,
others.
Our
results
experimental
non-diabetic
models
hypertension,
chronic
kidney
are
partially
consistent
these
findings.
This
raises
question
whether
same
mechanisms
at
work
conditions,
responsible
under
conditions.
Are
cardio-renal,
metabolic,
others?
review
will
focus
different
pathophysiological
namely
disease,
failure,
evaluated
rat
diseases.
Key
words:
inhibitor,
rat.
Язык: Английский
Sex specific considerations in cardiovascular drug therapy
Canadian Journal of Physiology and Pharmacology,
Год журнала:
2024,
Номер
102(9), С. 523 - 529
Опубликована: Сен. 1, 2024
Despite
major
advances
in
cardiac
research
over
the
past
three
decades,
cardiovascular
disease
(CVD)
still
remains
leading
cause
of
morbidity
and
mortality
women
men
worldwide.
However,
a
challenge
for
health
care
providers
is
that
current
guidelines
drug
therapies
do
not
consider
impact
sex
development
treatment
plan
optimizing
women.
Clinical
recent
years
suggests
significant
pharmacological
pharmacokinetic
differences
between
females
males,
which
have
been
attributed
part
to
body
composition,
plasma
protein
binding
capacity,
metabolism,
excretion.
Herein,
we
provide
comprehensive
review
regarding
sex-specific
drugs
commonly
used
CVDs
men.
Understanding
how
sex-related
influence
efficacy
CVD
outcomes
crucial
only
strategies
but
also
encourage
implementation
specific
address
difference
as
consideration
CVDs.
Язык: Английский