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Nephrotic Syndrome(NS)
Definition NS is an accumulation of sym
ptoms and signs and is characte
rized by proteinuria, hypoprote
inemia, edema, and hyperlipide
mia.
The vast majority patients (90% of cases) with NS of childhood are primary.
Definition In children under age 5 years the disease usually takes the form of idiopathic (primary) NS of childhood.
Conditions Of Attack● Second only to acute nephri- tis●Incidence age: at all ages, but most commonly between 3~5 years of age
Type
1. Clinical type
Simple type NS ;
Nephritic NS
2. Response to steroid therapy
(P274)
Type The initial response to cortico-
steroids is a guide to prognosis
● Steroid-dependent NS
● Steroid-responsive NS
● Steroid-resistant NS
Type ▲ Total effect
▲ Partial effect
▲ Non-effect
Type
3. Pathologic type (P282)
● Minimal change disease,
MCD – 80% of all NS, little
change on light microscopy,
Type but electron microscopy shows effacement of foot processes (podocytes) of epithelial cells
Type ●Other forms (Non-MCNS) MSPGN, FSGN, MGN, MPGN, etc.
Pathogenesis ◈ The primary disorder is an increase in glomerular permeability to plasma proteins→loss of proteins, mainly albumin in urine
Pathogenesis
◈ Filtrated barrier—
Charge barrier
Molecular barrier
◈ The loss of the negative
charges on the GBM
Pathogenesis ◈ The underlying pathogenesis
is unknown, but evidence
strongly supports the impor-
tance of immune mechanisms
(P281)
Pathophysiology 1. Proteinuria: fundamental
and highly important change
of pathophysiology
Pathophysiology 2. Hypoproteinemia: mainly
albumin
3. Edema: nephrotic edema
(pitting edema)
Pathophysiology ▲ Hypoproteinemia→plasma
oncotic pressure↓, result in
a shift of fluid from intervas-
cular to extravascular com-
partment →edema
Pathophysiology ▲Plasma volume↓→activates
the renin–angiotensin–aldo-
sterone system, also ADH
secretion↑→ Na and water
reabsorption↑
Pathophysiology
4. Hyperlipidemia (Hyper-
cholesterolemia):
Ch↑,TC↑, LDL-ch↑,
VLDL-ch↑
Pathophysiology Caused by:
1. Hypoproteinemia stimulates
liver protein synthesis including
lipoproteins;
2. Lipid catabolism↓(lipoprotein
lipases lost in urine?)
Clinical Manifestations Peak age: 2~5 years
Boys:girls = 3.7:1
1. Main manifestations
●Edema (varying degrees) is
the most common symptom,
+/- weight gain
Clinical Manifestations
● Edema of periorbital /face,
pitting edema in lower limbs,
perineum →anasarca evident
● Perhaps oliguria are noticed
● Ascites, pleural effusion
● Frothy urine
Clinical Manifestations
2. General symptoms: pallid,
anorexia, fatigue, diarrhea,
abdominal pain
Laboratory Exam
1. Urinary protein: 2+~ 4+
● 24 h total urinary protein
> 50 mg/kg/d or >0.1g/m2/d
( the most are selective
proteinuria )
Laboratory Exam
● UP/Ucr(mg/mg)>3.5
(normal 0.2)
● May occur RBC (15%),
granular and red cell
casts
Laboratory Exam 2. Total serum protein↓,
< 30 g/L
Albumin levels are low ,
often< 25 g/L
Laboratory Exam
3. Serum lipids↑
cholesterol(CH) > 5.7mmol/
L
triglycerides(TC)↑
LDL↑, VLDL↑
Laboratory Exam 4. ESR↑> 100 mm/h
5. Serum protein electrophoresis
Albumen↓, α2-G↑,γ-G↓,
A/G inversion
6. Serum Ca++ ↓
Laboratory Exam
7. Serum complement: vary
with clinical type
8. Renal function
BUN & serum Cr
Complications
1. Infections
▲Acute infection is a major
complication in children
with NS. It frequently
trigger relapses
Complications▲ Often precipitated by viral
infections
Site: respiratory tract(URI),
skin, urinary tract and acute
primary peritonitis
Complications
Due to: ★immunity lower
(urinary loss of IgG, etc.)
★severe edema→malcirculation
★ protein malnutrition
★ use steroid therapy
Complications 2. Electrolyte disturbances
2.1. Hyponatremia
2.2. Hypokalemia
2.3. Hypocalcemia
Complications3. Thromboembolic phenomena
( Hypercoagulability ):
Potential arterial & venous
thrombosis, e.g. renal vein
thrombosis
Complications Due to: urinary loss of antithrombinⅢ, hepatic fibrinogen synthesis↑, platelet aggregation↑etc.
Complications 4. Hypovolemia (Hypovolemic
shook)
5. Acute renal failure
6. Stunting
Diagnosis 1. Diagnostic standard (P273)
●Four characteristics
●Excluding other renal
disease (second NS)
Diagnosis2. Clinical type:
Simple type NS
Nephritic type NS
Management1. General measures
1.1. Rest
1.2. Diet
●Hypertension and edema:
low salt diet (<2 g Na/ day)
or salt-free diet
Management ●Generally do not restrict
oral fluid intake
●Severe edema: restrict fluid
intake and use diuretics
Management
●Increase proteins properly
1.5~2 g/kg/d
●While undergoing steroid
treatment: give VitD 400 iu/d
(or Rocaltrol) and calcium
Management 1.3. Prevent infection
1.4. Diuretics
● Not requires diuretics
usually
HCT 2~5 mg/kg/d
Management Antisterone 3~5 mg/kg/d
Triamterene
● Attention: Hypovolemia,
electrolyte disturbances
and embolism
Management● Apparent edema
Give low molecular dextran
10~15 ml/kg/time;[+Dopamine
2~3μg/kg/min) and Regitine
10 mg +Lasix 2 mg/kg]
Management 2. Corticosteroid therapy
—mainstay of treatment
2.1. Short-course therapy:
Prednisone 2 mg/kg/d
or 60 mg/m2/d (Max.
60 mg/d),
Management in 3 or 4 divided doses for
4 w→maintenance treatment:
Prednisone 1.5~2 mg/kg,
every- other- day, given as a
single, morning dose, for 4 w
Management
▲Total course of therapy: 8 w
2.2. Middle-course & long-
course therapy
① Induction of remission
Management Prednisone 2 mg/kg/d
(Max.60 mg/d) for 4 w →
until the urinary protein
falls to trace/ – (>V8w)→②
Management ② After maintenance treatment
Prednisone 2 mg/kg , single
dose for every-other-day×4 w
→tapered gradually (2.5~5
mg/ 2~4 wk) →discontinued
Management ▲Total course of treatment
Middle: 6 m
Long: 9~12 m
Estimate of curative effect
Management
3. Treatment of relapse and
frequently relapse
3.1. Extend the course of corti-
costeroid
3.2. Change preparation
Management3.3. Immunosuppressive agents
(Cytotoxic agents)
● CTX (Cyclophosphamide)
2~3 mg/kg/d for 8~12 w
Total amount: 200 mg/kg
Management Side effects: leukopenia,
trichomadesis, nausea,
vomiting, hemorrhagic
cystitis and fertility↓
Management
● CB (Chlorambucil)
0.2 mg /kg for 8 w
Total amount: 10 mg/kg
● 6-MP, VCR, MMF
Management
4. Impulsive therapy
4.1. Methylprednisolone (MP)
15~30 mg/kg(<1g/d+10%
GS 100~ 200 ml, iv drip
Management (within 1~2 h) , qd/qod, 3times
/one course, if necessary give
another 1~2 courses after 1
~ 2 w→prednisone
Management
4.2. CTX
10~15 mg/kg or 0.5~0.75
/m2 + NS or 5%GNS100~
200ml, iv drip (1~2 h),
every 2w for 6~8 times,
Management
total amount <150~200mg/kg
4.3. CsA
5~7 mg/kg, in 3 divided
doses for 3~6 m
expense, nephrotoxicity★
Management 5. Anticoagulants
Sodium Heparin 1mg/kg/d
+10%GS 50~100ml, qd,
for2~4w
Persantin 5~10 mg/kg/d,
for 6 m
Management6. Alleviate proteinuria
Angiotensin converting
enzyme inhibitions (ACEI):
Captopril, Enalapril and
Benazepril etc.
Prognosis Depend on histopathology
▲Most cases of MCNS
eventually remit per
-manently.
Prognosis ▲ Most (85%) NS will have
relapses; frequency of
relapse↓with age↑
Prognosis ▲ Nonresponsive to initial
steroid regimen (steroid-
resistant NS): most are
not MCNS, consider renal
biopsy
Thank you!
Thank you!