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. 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 (P 274 )

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 (P 282 ) ● 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 (P 281 )

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/m 2 /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↓, α 2 -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 antithrombin Ⅲ, hepatic fibrinogen synthesis↑, platelet aggregation↑etc.

Complications 4. Hypovolemia (Hypovolemic shook) 5. Acute renal failure 6. Stunting

Diagnosis 1. Diagnostic standard (P 273 ) ● 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 or 60 mg/m 2 /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/ – ( ≯ 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 corti- costeroid 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 /m 2 + 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 (steroid- resistant NS): most are not MCNS, consider renal biopsy

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