Transcript Document

Sindrom nefrotic la copii
Prezentator Angela Ciuntu,
conferenţiar universitar
Catedra Pediatrie nr.2
USMF “NicolaeTestemiţanu”
Nephrotic Syndrome
• Nephrotic syndrome is a common type of
kidney disease seen in children.
Historically, Roelans is credited with the
first clinical description of nefrothic
syndrome in the late fifteenth century,
whereas Zuinger later provided a detailed
description of the clinical course of the
disease and its importance as a cause of
chronic renal failure in the presteroid era.
Nephrotic syndrome is characterized
by
massive
proteinuria,
hipoalbuminemia,
and
edema,
although additional clinical features
such as hyperlipidemia are also
usually present. In the first few years
of life, children with or this condition
often show periorbital swelling with or
without generalized edema.
• Nephrotic syndrome develops when the
loss of protein in urine exceeds the rate of
albumin synthesis in the liver, resulting in
hypoalbuminemia and edema. Nephrotic
syndrome may be caused by variety of
glomerular and systemic diseases, but by
far the most common type in childhood is
idiopathic nephrotic syndrome. Before the
introduction of antibiotics, corticosteroids,
and other immunosuppressive therapies,
nephrotic syndrome was associated with
mortality as 67 %, usually following
infections.
• Between 1967 and 1974m the International
Study of Kidney Disease in Chidhood
(ISKDC) enrolled 521 children age 12 weeks
to 16 years with idiopathic nephritic syndrome
in order to evaluate the histopathologic,
clinical, and laboratory characteristics of
nephritic syndrome in children. The renal
biopsy studies demonstrated that about 80 %
of children had either minimal change
disease (MCD 76,4 %), focal and segmental
glomerulosclerosis (FSGS 6,9 %), or
mesangioproliferative glomerulonephritis
(Mes PGN 2,3 %).
• Subsequently the ISKDC
demonstrated that the response to
corticosteroids was higly predictive of
renal histology, with 93 % of children
with MCD achieving complete
remission following an 8-week course
of prednisone. However, between 25
% and 50 % of children with Mes
PGN or FSGS on biopsy also
responded of prednisone.
• At the moment there is no diagnostic
marker for children displaying with
nephrotic syndrome that can be used as a
predictor of steroid responsiveness or
resistance. The most important prognostic
marker for children with nephrotic
syndrome is their response to steroid
treatement. Initial steroid treatement can
be avoided only in patients with a family
history of SRNS or in those who have a
know gene mutation.
DEFINITIONS
TABLE 1. Definitions Used in Idiopathic Nephrotic Syndrome
Classification
Definition
Nephrotic syndrome
Edema, proteinuria > 40 mg/m2/hr or protein/creatinine ratio > 0,2 g/mmol (> 2
g/g) or 50 mg/kg/day or 3-4 + on urine dipstick, hypoalbuminemia < 25 g/L (< 2,5
mg/100ml)
Remission
Urinary protein excretion ≤ 4 mg/m2/hr or 0-trace of protein on urine dipstick or
protein/creatinine ratio < 0,02 g/mmol (< 2 g/g) for 3 consecutive days
Initial responder
Attainment of complete remission within initial 8 weeks of corticosteroid therapy
Initial
nonresponder/steroid
resistance
Failure to achieve remission during initial 8 weeks of corticosteroid therapy
Relapce
Urinary protein > 40 mg/m2/hr or protein/creatinine ratio> 0,2 g/mmol (> 2 g/g) or 2 +
protein or more on urine dipstick for 3 consecutive days
Infrequent relapce
One relapce within 6 months of initial response or one to three relapses in any 12- months
period
Frequent relapce
Two or more relapses within 6 months of initial response or four or more relapses in any
12- months period
Steroid dependence
Two consecutive relapses during corticosteroid therapy or within 14 days of ceasing
therapy
Late nonresponder
Proteinuria for > 8 weeks following one or more remissions
Nephrotic Syndrome: Diagnosis of nephritic
syndrome requires the presence of edema,
massive proteinuria (> 40 mg/m2/hr or a
urine protein/creatinine ratio > 2,0 mg/mg),
hypoalbuminemia (< 2,5 g/dl).
Remission: Remission is characterized by a
marked reduction in proteinuria (< 4
mg/m2/hr or urine albumin dipstick of to trace
for 3 consecutive days) in association with
resolution of edema and normalization of
serum albumin to at least 3,5 g/dl.
• Relapce: Relapce is defined as reccurence of
massive proteinuria (> 40 mg/m2/hr, urine
protein/creatinine ratio > 2,0 mg/mg, or urine
albumin dipstick ≥ 2 + on 3 consecutive
days), most often in association with
recurrence of edema.
• Steroid-Sensitive Nephrotic Syndrome:
Patients who enter remission in response to
corticosteroid treatment alone are referred to
as having steroid-sensitive nephrotic
syndrome (SSNS).
• Steroid-Resistant Nephrotic Syndrome: Among
pediatric nephrologists there are two definitions of
Steroid-Resistant Nephrotic Syndrome (SRNS). The
definitions introduced by the International Study of
Kidney Disease in Children (ISKDC) and used by the
Arbeitsgemeinschaft fȕr Pȁdiatrische Nephrologie
(APN) is widely accepted as follows: No urinary
remission within 4 weeks of prednisone therapy
60mg/m2/day. The other definition, employed by the
Society of French Speaking Pediatric Nephrologists,
states: No urinary remission following 4 weeks of
prednisone 60mg/m2/day followed by three
intravenous pulses of methylprednisolone.
• Steroid-Dependent Nephrotic Syndrome:
some patients respond to initial
corticosteroid treatment by entering
complete remission but develop a relapse
either while still receiving steroids or within
2 weeks discontinuation of treatment
following a steroid taper. Such patients
typically require continued low-dose
treatment with steroids to prevent
development of relapse, and are therefore
reffered to as having steroid-dependent
nephrotic syndrome (SDNS).
• Frequent Relapsing Nephrotic Syndrome:
patients in this goup enter complete remission
in response to steroids. Thery remain in
remission for several weeks following
discontinuation of treatment but develop
frequent relapses. If relapses occur 4 or more
times in any 12-months period, these patients
are referred to as having frequent relapsing
nephrotic syndrome (FRNS).
• Both SDNS and FRNS patients are at
increased risk of developing complications of
nephrotic syndrome and complications from
frequent use of steroids and other
immunosuppressive agents.
EPIDEMIOLOGY
• The incidence of SRNs varies throughout the world.
• In Europe, the United States, and Australia, the overall
incidence of idiopathic nephrotic syndrome is 1 to 3 per
100.000 children below age 16, with a cumulative
prevalence of 16 per 100.000 children. The incidence is
higher in Asian, African American, and Arab children. In
Asian children residing in northern England, the overall
rates are 7,4 (95 % confidence intervals [CI] 5,3-9,5) for
South Asian children compared with 1,6 (95 % CI 1,3-1,8)
per 100.000 children per year for non- South Asian
children with 88 % responsive to corticosteroids. In Libya
an incidence of 11,6 per 100.000 children was reported,
with 98 % responsive to corticosteroids. In African
American children, rates of 2,8 to 3,6 per 100.000 per year
have been reported compared with 1,8 to 2,3 in Caucasian
children.
• SSNS is more common in boys than in girls, with a
male/femaleratio of around 2:1 and a peak
incidence between 1 and 4 years. There is a
decreasing trend with increasing age in the
proportion with SSNS (Table 2). SSNS is
lesscommon in African and African American
children. In South Africa only 7,2 % of 236 African
children had SSNS compared with 62 % of 286
African children. In the past 2 decades the
proportion of children with idiopathic nephrotic
syndrome who respond to corticosteroids appears
to be falling when compared with 1978 ISKDC data.
Among 159 Canadian children age 6 months to 19
years, the proportion with SSNS fell from 81 %
between 1985 and 1993 to 65 % between 1993 and
2002; this was accompanied by an increase in
biopsy-documented FSGS have been reported from
South Africa and the United States.
• Age also correlates with both the frequeny of
presention and the biopsy findings associated eith
nephrotic syndrome. The most common age for
presentation is 2 years and 70 % to 80 % of cases
occur in children younger than. To somme extent age
also predicts the histologic lesion associated with
nephrotic syndrome. Children diagnosed bef age 6
represented 79,6 % of those with FSGS and only 2,6
% of those membranoproliferative glomerulonephritis
(MPGN). With these data were analyzed on the basis
of renal histology, median ages at presentation were
found to be 3 years excluding the first year of life,
these data combined su that the likelihood of having
MCNS decreases with increases age, whereas the
likelihood of having the less favorable diagnosis of
FSGS or MPGN increases.
• The histologic lesion associated with nephrotic
syndrome has important ramifications for the
likelihood of response steroid treatement. Although
almost 80 % of children diagnosed with nephrotic
syndrome in a multicenter International Study of
Kidney Diseases in Children (ISKDC) entered
remission following an initial 8-week course
prednisone, when these children were analyzed
based histology, steroid responsiveness was found
in 93 % of with MCNS compared with only 30 % of
those with FSGS and 7 % of those with MPGN. In
addition to histology response to steroids also vries
with geographic location ethnicity. Whereas 80 % of
children in western countries be steroid responsive,
studies from South Africa, Nigeria more recently
Ghana show that only 9 % to 50 % of children with
nephrotic syndrome are steroid responsive.
ETIOLOGY
• The etiology of nephrotic syndrome is also age
depend. Most cases appearing in the first 3
months of life are re as congenital nephrotic
syndrome (CNS) and are genetic diseases.
Although there has been no systematic of the
etiology of nephrotic syndrome presenting in the
the first year of life (3 to 12 months), there are
data sugg that up to 40% of cases during this
time may also be during genetic causes. Beyond
the first year of life and in the decade, most
cases are due to primary or idiopathic nephrotic
syndrome cases increases beyond the first 10
years of life.
ETIOLOGY AND PATHOGENESIS
• A T-Cell Disease
• In 1974 a series of clinical observations led Dr.
Shaloub to propose that SRNS was due to an
abnormality in T-cell function. Nephrotic syndrome
had been observed in patients with Hodgkins
lymphoma and cases of thymoma. The desease
was noted to remit in children who had measles,
which led some to propose using measles as a
therapeutic strategy. A major effect of the measles
virus is that it inhibits cell-mediated immunity,
thereby shutting down T-cell function. Furthermore,
the response of nephrotic syndrome to T-cell
suppressive agents such as steroids or calcineurin
inhibitors also supported their role in nephrotic
syndrome. These features all suggest that
lymphocytes are key cells in SSNS.
• A Circulating Factor
• MCD appears to exist in a spectrum with FSGS. A
proportion of children with MCD on clinical and
histologic grounds develop FSGS. In both there
appears to be a circulating factor, with FSGS
children being less responsive to therapeutic
agents for various reasons. Within this group is a
subset of children in which the disease resides in
structural changes in the glomeruli with genetic
mutations in key glomerular slit process proteins,
including nephrin, podocin, Actinin 4, and WT-1.
These are described elsewhere but in brief are
associated with no response to steroids and
progression to endstage renal failure, and do not
show evidence of a circulating factor as
demostrated by rapid recurrence of disease in a
transplanted kidney.
• The timing of response with the return to
normal function taking days to weeks is
also supportive of slow podocyte recovery
from an injurious cytokine. The higher
rates of recurrence in children with FSGS
receiving living-related kidneys suggests
that there may be a degree of HLA
restriction of response, which is also
supported by HLA-linkage studies showing
that increased incidence of desease is tied
to certain alleles such as HLA B8, B13,
DWQ2, DQB10301, and DR7.
• Over the years vartous growth factors and
cytokines have been proposed as pathogenic in
SSNS. The initial identification of the vascular
permiability factor (VPF), now called vascular
endothelial growth factor (VEGF), was thought
to have identified the key protein leading to
nephrotic syndrome. However, identification of
this protein in norm urine delayed further
investigation of its role. More recen it has been
noted to be increased in urine during relapses
nephrotic syndrome though circulating levels
are unchange suggesting that VEGF levels
reflect the concomitant proteinuria.
• Recent tissue-restricted knockouts of VEGF
in mice restricted to podocytes have
demonstrated a key role for loc VEGF in
maintaining glomerular endothelial integrity
and again have reinforced its importance,
though perhaps more locally, in maintaining
permeability. Soluble immun response
suppressor (SIRS) was also identified as a
cytokine in patients with SRNS, but again the
inability to consistent characterize this protein
despite many mechanistic observations led to
its exclusion as the likely factor.
• Other circulating factors have been proposed,
and development of a functional assay of
glomerular permeability by Dr. Savin in the late
1990s identified a proteinuric factor that was
small, highly glycosylated, and hydrophobic.
The appeared likely to allow fractionation of
nephrotic sera, wh would allow identification of
the factor. Other, observation that protein A
coluns could remove the nephrotic factor
posttransplant also seemed to point to
identifying features.
PATHOGENESIS
• The central abnormality in all cases of
nephrotic syndrome is the development of
massive proteinuria. Although the
molecular basis for this is still speculative,
there is evidence in the literature that
nephrotic syndrome may be a
consequence of a primary glomerular
defect, circulating factors, or an
immunological abnormality.
• Primary Glomerular Defect
• One of the most important functions of the
kidney is the filtration of blood by glomeruli,
which allows excretion of fluid and waste
products while retaining the majority of
blood proteins and all blood cells within the
vasculature. This process of filtration is
made possible by the glomerular filtration
barrier, which is made up of specialized
fenestrated endothelial cells, the glomerular
basement membrane (GBM). Neighboring
podocyte foot processes are connected to
each other by networks of specialized cellcell junctions known as slit diaphragms.
• In addition, the GBM has an abundant supply
of negatively charged heparin sulfate
proteoglycan, resulting in negatively charged
molecules being relatively more restricted
from passage than positively charged
molecules of the same size. In health,
molecules greater than 42 A in diameter, or
more than 200 kDa, are unable to cross the
filtration barrier. This restriction depends
largely on the structural integrity of the
podocyte foot processes and slit diaphragms,
as well as the GBM charge. In nephrotic
drome there of negative charge of the GBM.
• O morphologic changes in
podocytes that occur during
development of nephrotic
syndrome include sweiling,
retraction, effacement (spreading)
of the podocyte distal foot proces
vacuole formation, occurrence of
occluding junctions, placement of
slit diaphragms, and detachment
of podocyte from the GBM.
• The importance of podocyte and
slit diaphragm struc to the
pathogenesis of nephrotic
syndrome is further forced by
recent observations in humans
and axperiment animals that
mutations in genes encoding
some of the diaphragm proteins
or their transcription factors can
SRNS and/or FSGS.
Table 2. Etiologies of Nephrotic Syndrome (Beyond 3 Months of Age)
Idiopathic
Minimal change nephrotic syndrome (MCNS)
Focal segmental glomerulosclerosis (FSGS)
Mesangial proliferative glomerulonephritis
Membranoproliferative glomerulonephritis (MPGN)
Membranous nephropathy (MN)
Ig M nephropathy
Ciq nephropathy
Genetic
Autosomal recessive FSGS due to mutation in gene encoding
podocin (NPHS2)
Autosomal dominant diffuse mesangial sclerosis (DMS) due to
mutation in gene encoding WTI
Autosomal dominant FSGS due to mutation in gene encoding αactinin 4
Autosomal dominant FSGS due to mutation in gene encoding
CD2-associated protein (CD2AP)
Autosomal dominant FSGS due to mutation in gene encoding
transient receptor potential cation chan 6 (TRPC6)
Infections
Hepatitis B and C
HIV
Malaria
Schistosomiasis
Filariasis
Systemic disease
Henoch-Schonlein purpura
Systemic lupus erythematosus
Diabetes mellitus
Sarcoidosis
Metabolic disease Fabry's disease
Glutaric acidemia
Glycogen storage disease
Mitochondrial cytopathies
Hematologic and
oncologic disease
Leukemia
Lymphoma (Hodgkin's most likely can lead minimal
change)
Sickle cell disease
Drugs
Nonsteroidal antiinflammatory drugs (NSAIDs)
Gold
Penicillamine
Angiotensin converting enzyme inhibitors (ACEIs)
Pamidronate
Interferon
Mercury
Heroin
Lithium
Others
Bee stings (MCNS)
Food allergies
Obesity (usually with FSGS)
Oligomeganephronia
Pregnancy
• Circulating factors
• There are experimental data to support the
existence of soluble mediators that may alter
capillary wall permeability in nephrotic syndrome.
Evidence for this includes development of
nephrotic syndrome in newborn babies born to
mothers with nephrotic syndrome who apparently
transferred a soluble factor to their fetuses in utero,
marked reduction of proteinuria following
treatement with protein A immunoadsorption in
various types of primary nephrotic syndrome,
recurrence of FSGS in transplanted kidneys in
patients with induced by treatement with protein A
immunoadsorption due to presumed removal of
circulating factors, and induction of enhanced
glomerular permeability in experimental animals
injected with serum from patient with FSGS
recurrence in transplanted kidneys.
• Furthertmore, inhibitors of glmerular
permeability have also been isolated
from the serum of children with FSGS
and identified as components of
apolipoproteins, suggesting that an
imbalance between serum
permeability factors and permeability
inhibitors may have a pathogenic role
in FSGS.
• Immunological Abnormality
• The theory that nephrotic syndrome may be
due to dysregulation of the immune system
has existed for more than 30 years. There
are numerous reports of abnormalities of
both the humoral and cellular immune
responses during relapse of nephrotic
syndrome. However, the idea that nephrotic
syndrome may be due to dysregualtion of T
lymphocyte function was first proposed by
Shalhoub and his colleagues.
• Immunological Abnormality
• The theory that nephrotic syndrome may
be due to dysregulation of the immune
system has existed for more than 30
years. There are numerous reports of
abnormalities of both the humoral and
cellular immune responses during relapse
of nephrotic syndrome. However, the idea
that nephrotic syndrome may be due to
dysregualtion of T lymphocyte function
was first proposed by Shalhoub and his
colleagues.
• Other reports have also suggested an important
role of the cell-mediated immunyti during
relapses of MCNS alterations in t cell subsets
during relapses, and increased cell surface
expression of IL-2 receptors on T cells,
reflective of T cell activation. In addition,
numerous cytokines, released in part by T
lymphocytes, have been reportedto be variably
altered during nephrotic syndrome. It should be
noted, however, that despite numerous reports,
none of these cytokines has proven to be both
present in the majotity of cases of MCNS and
able to induce significant proteinuria in
experimental animals.
CLINICAL FEATURES AND
DIAGNOSIS
• History and Physical Examination
• In a child with periorbital or generalized
edema, the primary care physician can
quickly make this diagnosis by documenting
significant proteinuria with more than 2+
albumin on urine dipstick or a spot urine
protein/creatinine ratio greater than 2 mg/mg
and serum albumin of less than 2,5 g/dl. In
addition, a careful history should exclude
possible complications and identify children
with atypical presentations that might reflect
other serious systemic illnesses.
• It should include an evaluation of any
abdominal distension, which is usually due to
ascites and sometimes tension may be
accompanied by abdominal discomfort,
persistent abdominal pain may be abdominal
discomfort, persistent abdominal pain may be
due to primary bacterial peritonitis (a
potentially life-threatening complication), gut
edema, or relative gut ischemiadue to
hypoperfusion secondary to intravascular
volume depletion. Other causes of an acute
abdomen should also be considered.
• Regarding physical examination, blood
pressure should be carefully determined in
nephrotic children, it can be either low (due
to intravascular volume depletion) or
elevated (due to neurohumoral responses to
hypovolemia, intrinsic renal causes, or
occasionally renal vein thrombosis).
Hypertension has been reported in up to 21
% of children 6 years and under with biopsyconfirmed MCNS, and may be present in up
to 50 % of children with other histologic
types.
• Laboratory Evaluation
• Diagnosis of nephrotic syndrome is
confirmed by the triad of generalized
edema, proteinuria, albuminuria (> 2+ on
dipstick or urine protein/creatinine ratio
(>2mg/mg), and hypoalbuminemia
(serum albumin < 2,5 g/dl), although
hypercholesterolemia is also commonly
present.
• In patients with a typical presentation, serum
studies should include an evaluation of
complete blood count, electrolytes, blood
urea nitrogen (BUN), creatinine, and albumin
levels. For patients at an older age at
presentation or with atypical presentation,
additional serum studies to exclude
secondary causes of nephrotic syndrome
should include C3 and C4 complement
levels; antinuclear antibody (ANA) and
possibly anti-double-stranded DNA; HIV
antibody; hepatitis A, B, and C serologies,
and consideration of other viral serologies
such as HIV antibodies.
• Because immunosuppressive therapy is the
mainstay of treatment for most cases of childhood
nephrotic syndrome, many pediatric nephrologists
recommend placing a PPD (purified protein
derivative) test to screen for occult tuberculosis
before instituting immunosuppression.
• Renal ultrasound does not usually have a role in
the evaluation of childhood nephrotic syndrome.
However, in thesetting of a nephrotic child who
develops gross hematuria, thrombocytopenia, or
unexplained persistent hypertension, renal
ultrasound should be considered to exclude
possible development of renal vein thrombosis.
• Renal Biopsy
• More than 80 % of children with idiopathic
nephrotic syndrome will respond to steroid
therapy by entering complet remission. Based
on this statistic, an initial trial of 4 weeks of
high-dose daily steroid therapyis usually
prescribe in children under 10 before
considering renal biopsy. Is general, renal
biopsy is indicated only in the setting of atypical
features such as age at onset (less than 1 year
or m than 10), SDNS or SRNS, gross or
persistent microscopic hematuria or presence
of red cell casts, abnormal serologies, or
significant persistent renal failure.
TREATMENT OF NEPHROTIC
SYNDROME
• Specific Therapy
• The initial treatement for new-onset nephrotic syndrome erally
includes 60mg/m2/day (maximum 80 mg/d) of prednisone for 4
to 8 weeks, followed by 40mg/m2 every e day for 4 to 8 weeks,
and then a gradual taper until discontinued.
• In patients, FRNS and SDNS, alternative agentswith potential
steroid sparing effects are often used, including
cyclophosphamide, levamisole, cyclosporine, tacrolimus, and
mycophen mofetil. In patients with SRNS, however, the most
monly used agents include cyclosporine, tacrolimus, hi dose
intravenous methylprednisolone, and mycopheno mofetil
(MMF), although the efficacy of almost all tha agents is lower in
these patients compared with FRNS SDNS patients.
General Management
• Edema
• Patients with nephrotic syndrome have
increased total b fluid and sodium during
active disease. General measure control
edema include salt restriction, moderate fluid
restriction, and judicious use of diuretics.
Dietary recommendation include
maintenance of protein intake at
approximately to 140 % of the RDA for age,
as well as avoidance of satural fats that can
worsen hyperlipidemia.
• Because the intravascular volume status in
children nephrotic syndrome is typically low,
diuretics should ally be used only when
significant intravascular depi has been either
excluded or corrected. Typically corre of
intravascular depletion can be achieved by ini
intravenous 25 % albumin at 1-2 g/kg/d either
as a contin infusion or divided q 6-8 hours.
Albumin treatement should continue for 4 to 6
hours before initial administration of diuretics
to minimize the risk of worsening any
intravascular volum depletion that may be
present.
• The most commonly used diuretic in this setting
is the loop diuretic furosemide. It acts by
inhibiting the sodium-potassium-2 chloride
transporter in the thick ascending limb of the
loop of Henle. During nephrotic syndrome,
however, several factors may impair its efficacy.
Because furosemide is higly protein bound,
hypoalbuminemia may result in reduced
delivery of albumin- bound furosemide to the
proximal tubular cells for secretion into the
tubular lumen. Hypoalbuminemia also causes
an increased volume of distribution of
furosemide due to diffusion of the free drug into
the expanded interstitial compartment.
• Measures to overcome resistance to furosemide
include increased dose, coadministration with albumin,
and coadministration with distal tubular diuretics.
Doses ranging from 200 % to 300 % of normal can
often achieve the desired clinical effects, although
high doses in the presence of significant renal
impairment may increase the risk for ototoxicity, which
has been shown to be related to the peak levels.
Clinically effective dosing strategies for intravenous
furosemide in nephrotic children with normal renal
function typically range from 0,5-1 mg/kg q 6-12 hours,
although reports in children with cardiac disease have
shown that continuous infusion of furosemide results
in a more efficient diuresis compared with intermittent
administration.
• When diuretics are used,
physicians should watch closely
for common and serious side
effects of 3 agents, which include
increased risk of thrombosis,
electrolyte disturbances such as
hypokalemia and metabolic
alkalosis, pypercalciuria and
nephrocalcinosis, and ototoxicity.
• Hyperlipidemia
• Hyperlipidemia is commonly found in
children with nephrotic syndrome. The
characteistic lipid profile includes
elevations in total plasma cholesterol,
very-low-density lipoprotein (VLDL), and
low-density lipoprotein (LDL) cholesterol,
triglyceride, and lipoprotein A, as well as
variable alterations (more typically
decreased) in high-density lipoprotein
(HDL) cholesterol.
• Although hyperlipidemia in children
with SSNS is often transiet and
usually returns to normal after
remission, children with SRNS
refractory to therapy often have
sustained hyperlipidemia.
• The potential usefulness of
hydroxymethylglutaryl CoA (HMG
CoA) reductase inhibitors (statins) in
children with SRNS has been
reported in a few uncontrolled trials.
• Antiproteinuric Agents
• Angiotensin converting enzyme inhibitors
(ACEIs) are increasingly being used in the
management of persistent proteinuria and
control of hypertension in children with SRNS or
SDNS. The antiproteinuric effects of ACEIs are
due to thein ability to reduce glomerular
capillary plasma flow rate, decrease
transcapillary hydraulic pressure, and alter the
permselectivity of the glomerular filtration
barrier.
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COMPLICATIONS
Infection
Thromboembolism
Cardiovascular Disease
Respiratory Distress
Bone Disease
Acute renal Failure
Other Complications
TABLE 3. Complications of Nephrotic Syndrome
Infectious
Cardiovascular
Respiratory
Peritonitis
Cellulitis
Disseminated
Varicella
Infection
Hypertension
Hyperlipidemia
Coronary artery disease
Pleural effusionPulmonary embolism
Venous (more common) or arterial
(less common) thrombosis
Anemia
Gastrointestinal Intussusception
Hematologic
Renal
Acute renal failureRenal vein
thrombosis
Endocrinologi Reduced bone mineral
densityHypothyroidism, clinical and
c
subclinical (more common in CNS)
Neurologic
Cerebral venous thrombosis
Treatement-related
General
Infection, hypertension
Steroids
Growth impairment, reduced bone density,
posterior capsular cataracts, avascular
necrosis of femoral head
Alkylating agents
Hemorrhagic cystitis, dose-related
oligospermia and premature ovarian failure,
increased risk of malignancy
Calcineurin
inhibitors
Gingival hyperplasia, hirsutism,
hyperkalemia, encephalopathy
Mycophenolate
mofetil (MMF)
Nausea, vomiting, diarrhea, constipation,
dose-related leukopenia, headache
PROGNOSIS
• The single most important prognostic factor for
maintenance of long-term normal renal
function in nephrotic syndrome is the patient's
initial response to corticosteroids. Although
children who enter complete remission during
an 8-week initial course of oral corticosteroids
have an excellent prognosis, the prognosis for
those who fail to enter remission is more
guarded. Overall, close to 80 % of newly
diagnosed children treated with corticosteroids
will achieve complete remission.
•