Nephrotic Syndrome (NS)

Definition NS is an accumulation of symptoms and signs and is characterized by proteinuria, hypoproteinemia, edema, and hyperlipidemia.

The vast majority patients (90% of cases) with NS of childhood are primary. 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 (P 331 )

The initial response to cortico- steroids is a guide to prognosis. (1) Total effect (2) Partial effect (3) Non-effect

3. Pathologic type (P 328 ) 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 (P 328 ).

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 + ～ hr 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↓, α 2 -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 (P 330 ): ● 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/m 2 /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: ① Induction of remission: Prednisone 1.5~2mg/(kg · day) (Max.60mg/day) for 4wk until the urinary protein falls to trace or negative levels ②

② After 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 (P 331 ).

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/m 2 + NS/GS iv drip (1hr), give liquid 2,000ml /(m 2.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.