Transcript Nephrotic syndrome, NS

Nephrotic
Syndrome(NS)
Definition
NS is an accumulation of
symptoms and signs and is
characterized by proteinuria,
hypoproteinemia, edema, and
hyperlipidemia.
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 corticosteroids 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 importance 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 intervascular to extravascular compartment →edema
Pathophysiology
▲Plasma volume↓→activates
the renin–angiotensin–aldosterone 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:
● 24
+
+
2 ～4
h total urinary protein
2
> 50 mg/kg/d or >0.1g/m /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
Complications
3. 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)
Diagnosis
2. Clinical type:
Simple type NS
Nephritic type NS
Management
1. 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
2
or 60 mg/m /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 & longcourse 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/ – (≯8w)→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 corticosteroid
3.2. Change preparation
Management
3.3. 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
2
/m + 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
Management
6. 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 (steroidresistant NS): most are
not MCNS, consider renal
biopsy
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