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

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