Nephrotic Syndrome (NS)

Definition NS is an accumulation of

symptoms and signs and is

characterized by proteinuria,

hypoproteinemia, edema, and

hyperlipidemia.

In children under age 5 years the disease usually takes the form of idiopathic (primary) NS of childhood (nil disease, lipoid Nephrosis).

Conditions Of Attack Second only to acute nephri-tis. Incidence age: At all ages, but most commonly between 2~5 years of age.

Type

1.Clinical type

Simple NS ; Nephritic NS

2.Response to steroid therapy

(P331)

The initial response to cortico-

steroids is a guide to prognosis.

(1) Total effect

(2) Partial effect

(3) Non-effect

3. Pathologic type (P328)

Minimal change disease,

MCD: 80% of patients.

Pathogenesis The primary disorder is an increase in glomerular permea- bility to plasma proteins. ▲Foot processes of the visceral epithelium of the GBM.

1.The construction of the

glomerular basement memb-

rane has changed.

2.The loss of the negative

charges on the

GBM.

◆The underlying pathoge-

nesis is unknown, but evidence

strongly supports the impor-

tance of immune mechanisms

(P328).

Pathophysiology

1.Proteinuria: Fundamental

and highly important change of

pathophysiology.

2.Hypoproteinemia (mainly

albumin)

3.Edema: Nephrotic edema

(pitting edema)

Hypoproteinemia plasma

oncotic

pressure is diminished, result

in a shift of fluid from the

vascular to the interstitial

compartment and plasma

volume↓→the activation of

the renin–

angiotensin–aldo-

sterone system→ tubular

sodium chloride reabsorp-

tion↑.

4. Hyperlipidemia (Hyper-

cholesterolemia)

Ch↑, TG↑, LDL-ch↑,

VLDL-ch↑.

Clinical Manifestations There is a male preponderance

of 2:1.

1.Main manifestations: Edema

(varying degrees) is the common

symptom.

Periorbital swelling and

perhaps oliguria are noticed

→→increasing edema→→

anasarca evident.

2.General symptoms:

Pallid,

anorexia, fatigue,

abdominal pain, diarrhea.

Laboratory Exam 1.Urinary protein: 2+～ 4+

24hr total urinary protein

> 0.1g/kg.

( The most are selective

proteinuria. )

May occur granular and red

cell casts.

2.Total serum protein↓,

＜ 30g/L .

Albumin levels are low (＜20g/L).

3.Serum cholesterol and

triglycerides:

Cholesterol ＞ 5.7mmol/L

(220mg/dl).

4. ESR↑＞ 100mm/hr.

5.Serum proteins electro-

phoresis :

Albumin↓, α2-G↑,γ-G↓,

A/G inversion.

6.Serum complemen: Vary

with clinical type.

7.Renal function:

Complications

1.Infections

Infections is a major compli-

cation in children with NS. It

frequently trigger relapses.

Site: Respiratory tract, skin,

urinary tract and acute pri-

mary peritonitis.

Causes: Immunity lower ,

severe edema→malcirculation,

protein malnutrition, and use

hormone and immunosuppre-

ssive agents.

2.Electrolyte disturbances

(1) Hyponatremia

(2) Hypokalemia

(3) Hypocalcemia

3.Thromboembolic phenomena

( Hypercoagulability )

Renal vein thrombosis

4.Hypovolemic shook

5.Acute renal failure (prerenal)

Diagnosis 1.Diagnostic standard (P330):

●Four characteristics.

●Excluding other renal disease

(second nephrosis).

2.Clinical type

Simple NS or Nephritic NS.

Treatment

1.General measures

1.1 Rest

1.2 Diet

Hypertension and edema:

Low salt diet (<2gNa/ day) or

salt-free diet.

Severe edema: Restricting

fluid intake.

Increase proteins properly:

2g/(kg·day)

While undergoing the corti-

costeroid treatment: Give VitD

500~1000iu/day (or Rocaltrol)

and calcium.

1.3 Prevent infection

1.4 Diuretics

Not requires diuretics

usually.

＊ HCT 2~5mg/(kg · day)

＊ Antisterone 3~5mg/(kg ·

day)

＊ Triamterene

Attention: Volume

depletion, disorder of

electrolyte and embolism.

Apparent edema:

Give low molecular dextran

10~15ml/(kg·time);

[+Dopamine 2~3ug/(kg·min)

and/or Regitine 10mg +Lasix

1~2mg/kg].

2.Corticosteroid therapy

Short-course therapy:

Prednisone 2mg/(kg·day) or

60mg/m2/day (Max.60mg/day)

in 3 or 4 divided doses for 4wk

→maintenance treatment:

Prednisone 1.5mg/kg, single

dose for every-other day×4wk.

▲Total course of therapy: 8

wk.

Middle-course & long-course

therapy:

Induction of remission:① Prednisone 1.5~2mg/(kg · day)

(Max.60mg/day) for 4wk until

the urinary protein falls to

trace or negative levels ②

②After maintenance

treatment:

Prednisone 2mg/kg , single

dose for every-other-day×4wk

tapered gradually (2.5~5

mg/2wk) discontinued.

▲Total course of treatment :

★Middle: 6mo

★Long: 9~12mo

Estimate of curative effect

(P331).

3. Treatment of relapse and

recurrence

3.1 Extend the course of corti-

costeroid

3.2 Immunosuppressive agents

(Cytotoxic agents):

① CTX (Cytoxan)

2mg/(kg·day) for 8~12wk .

Total amount: 250mg/kg

Side effects: nausea,

vomiting,

WBC↓, trichomadesis, hemo-

rrhagic cystitis and the damage

of sexual glands.

② CB (Chlorambucil)

0.2mg/kg for 8wk .

Total amount : 10mg/kg

③ VCR & Levamisole

4.Impulsive therapy

(1) Methylprednisolone (MP)

15~30mg/kg(<1g/day+10%

GS 100~ 250ml, iv drip (within

1~2hr) , 3 times/one course. If

necessary, give another 1~2

courses after 1~2wk

prednisone 2mg/kg, qod

tapered gradually.

(2) CTX

0.5~0.75mg/m2 + NS/GS iv

drip (1hr), give liquid 2,000ml

/(m2.d) .

Every one mo for 6~8 times.

(3) CsA

5~7mg/kg, in 3 divided doses

for 3~6mo.

★expense and nephrotoxicity.

(4) Anticoagulants

Heparin

Persantin 5mg/(kg·day） for

6mo.

5.Alleviar proteinuria

Angiotensin converting en-

zyme inhibitions (ACEI) :

Captopril, Enalapril and

Benazepril.

Prognosis Most cases of minimal

change disease eventually

remit permanently.