c:\documents and settings\administrator\桌面\20100607 nephrotic syndrome

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Department of pediatricsDepartment of pediatricsThe first affiliated hospitalThe first affiliated hospital

Sun Yat Sen UniversitySun Yat Sen University

Sun LiangzhongSun Liangzhong ( ( 孙良忠孙良忠 ))

sunlzh@mail.sysu.edu.cn

Nephrotic Syndrome

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DefinitionDefinition

Glomerular permeability↑Glomerular permeability↑ Clinical featuresClinical features

– Massive proteinuriaMassive proteinuria

– HypoproteinemiaHypoproteinemia

– HyperlipidemiaHyperlipidemia

– EdemaEdema

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ClassificationClassification

Primary/Idiopathic (90%)Primary/Idiopathic (90%)

Secondary: Secondary:

– SLE, HBV, anaphylactoid purpuraSLE, HBV, anaphylactoid purpura

Congenital/hereditaryCongenital/hereditary

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Idiopathic Nephrotic SyndromeIdiopathic Nephrotic Syndrome

Etiology and PathogenesisEtiology and Pathogenesis– Immunologic mechanismsImmunologic mechanisms– T-lymphocyte AbnormalitiesT-lymphocyte Abnormalities– Glomerular permeability factorGlomerular permeability factor

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a Basement membraneb Epithelial cellc Endothelial celld Mesangial cell

Glomerular filtration barrier

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Glomerular filtration barrier

a Basement membraneb Epithelial cellc Endothelial celld Mesangial cell

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Glomerular filtration barrierGlomerular filtration barrier

– Size-selective (aperture) Size-selective (aperture) barrierbarrier

– Charge-selective barrierCharge-selective barrier

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aperture barrier

Endothelium

slit diaphragm

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Charge-selective barrier

Endothelium

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1313Nonselective proteinuria

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minimal change disease (MCD) mesangial proliferative glomerulone

phritis (MsPGN) focal segmental glomerulosclerosis

(FSGS) membranous nephrosis (MN) membranoproliferative glomerulone

phritis (MPGN)

Pathological changes in INS

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Mild Moderate

Mesangial proliferative glomerulonephritis

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Focal segmental glomerulosclerosis (FSGS)

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membranous nephrosis (MN)

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Membranoprliferative glomerulonephritis

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Pathological patterns of INS in Pathological patterns of INS in children and adultschildren and adults

Children

66%3%8%4%9%10% 22%

2%8%

33%2%

33%

MCNS

MsPGN

FSGS

MN

MPGN

Others

Adults

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PathophysiologyPathogenetic factor

glomerular permeability↑

massive proteinuria

Hypoproteinemialipoproteins synthesis↑

hyperlipidemia

Plasma oncotic pressure↓

Intravascular volume↓

RAA(aldosterone)↑ ADH↑

Watersodium retention

Edema

Fluid

Interstitial space

Lipoprotein lipase↓

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Clinical manifestation

Epidemiology

Incidence, sex and age

Main symptoms and signs

Edema 、 ascites 、 pleural effusio

n

Urine, hematuria

Blood pressure

Renal function

Genaral situation

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Urine• Urinalysis, 24h urinary protein excretion,

urinary Pro/Cr

Serum• albumin, cholesterol, triglyceride• IgG, IgA, IgM, C3• BUN, Cr • sodium, potassium, calcium

Ultrasonographyrenal biopsy

Laboratory testsLaboratory tests

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Diagnosis and classifications

• 24h urinary protein excretion ＞50/40mg/kg/d

• Serum albumin ＜ 25g/L

• Serum cholesterol ＞ 5.72mmol/

L

• Edema

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• Hematuria Urinary RBC≥10/HPF

• Hypertension: Preschool age child≥120/80mmHg School age child≥130/90mmHg

• Renal function insufficient• Hypocomplementemia

Simple type and Nephritic type

Clinical types

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Differential diagnosis What are the related diseases?What are the related diseases?

Edema caused by renal diseasesEdema caused by renal diseases ？？ Nephrotic syndromeNephrotic syndrome ？？ Primary, secondary or congenitPrimary, secondary or congenit

alal ？？ Simple type or nephritic typeSimple type or nephritic type ？？

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Treatment

General treatment

RestRest DietDiet – Sodium and waterSodium and water

– ProteinProtein

– calcium and vitamin Dcalcium and vitamin D

DiuresisDiuresis

Education of the familyEducation of the family

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SteroidSteroid– Prednisone, methyl-prednisolonePrednisone, methyl-prednisolone

Treatment

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Corticosteroid therapyCorticosteroid therapy

SchemeScheme– Short courseShort course

– Mediate courseMediate course

– Long courseLong course

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Prednisone 1.5-2 mg/kg/d*6-8w Prednisone 1.5-2 mg/kg/d*6-8w

Prednisone 2mg/kg qod*4wPrednisone 2mg/kg qod*4w

Prednisone dose (every 2-4w)Prednisone dose (every 2-4w)

Course of treatmentCourse of treatment

6m 9m6m 9m

Intermediate longIntermediate long

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steroid responsive/sensitive

steroid resistant / insensitive

steroid dependent

frequent relapse

classification on curative effects

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– Metabolic disturbanceMetabolic disturbance

– HypertensionHypertension

– Infection, peptic ulcerInfection, peptic ulcer

– Euphoria, lunacy, induce epilepsy, Euphoria, lunacy, induce epilepsy, insomniainsomnia

– Osteoporosis, growth retardationOsteoporosis, growth retardation

– CataractCataract

– abuse syndrome and adrenal abuse syndrome and adrenal insufficiencyinsufficiency

Side effects of corticosteroid

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– frequent relapsefrequent relapse

– steroid dependentsteroid dependent

– steroid resistantsteroid resistant

– unable to tolerate steroid treatmentunable to tolerate steroid treatment

Indications forIndications for Alternative agentsAlternative agents

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Alternative agentsAlternative agents for INSfor INS

Cyclophosphamide (CTX)Cyclophosphamide (CTX)

Cyclosporine (CsA) and tacrolimus (FKCyclosporine (CsA) and tacrolimus (FK

506) 506)

Mycophenolate, MMFMycophenolate, MMF..

Angiotensin-converting enzyme inhibitoAngiotensin-converting enzyme inhibito

rs (ACEI) and angiotensin II blockersrs (ACEI) and angiotensin II blockers

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Cyclophosphamide (CTX)Cyclophosphamide (CTX)

Cyclophosphamide prolongs the duratiCyclophosphamide prolongs the durati

on of remission and reduces the numbeon of remission and reduces the numbe

r of relapses in children with r of relapses in children with frequently frequently

relapsingrelapsing and and steroid-dependent nephrsteroid-dependent nephr

otic syndromeotic syndrome. .

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– LeukopeniaLeukopenia

– AlopeciaAlopecia

– Hepatic function disorderHepatic function disorder

– Hemorrhagic cystitisHemorrhagic cystitis

– SterilitySterility

– Disseminated varicella infectiDisseminated varicella infectionon

– Inappropriate ADH secretionInappropriate ADH secretion

Side effects of CTX

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Cyclosporine and tacrolimusCyclosporine and tacrolimus

CyclosporineCyclosporine (3–6 mg/kg/24 hr divided q (3–6 mg/kg/24 hr divided q 12 hr) 12 hr)

Tacrolimus Tacrolimus (0.15 mg/kg/24 hr divided q 1(0.15 mg/kg/24 hr divided q 12 hr) 2 hr)

Both are also effective in maintaining pBoth are also effective in maintaining prolonged remissions in children with nerolonged remissions in children with nephrotic syndrome and are useful as stephrotic syndrome and are useful as steroid-sparing agents. roid-sparing agents.

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Side effects of CSA and FK506

HypertensionHypertension

NephrotoxicityNephrotoxicity

HirsutismHirsutism

gingival hyperplasia gingival hyperplasia

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Mycophenolate and ACEIMycophenolate and ACEI

Mycophenolate Mycophenolate may maintain remission may maintain remission in children with steroid-dependent or frin children with steroid-dependent or frequently relapsing nephrotic syndrome.equently relapsing nephrotic syndrome.

ACEI and angiotensin II blockersACEI and angiotensin II blockers may b may be helpful as adjunct therapy to reduce pe helpful as adjunct therapy to reduce proteinuria in steroid-resistant patients. roteinuria in steroid-resistant patients.

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OthersOthers

Anticoagulant therapyAnticoagulant therapy

– Heparin, PersantineHeparin, Persantine

Immunologic regulatorsImmunologic regulators

Chinese medicineChinese medicine

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Complications

• Infection

• Electrolyte disorder, Hypovolemia

• Hypercoagulability and thrombosis

• Acute renal failure

• Renal tubular function disorder

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Infection• Manifestations

• URI, spontaneous peritonitis, tuberculosis, cellulitis, urinary tract infection

• Cause• Immunoglobulin and complement factor↓• protein malnutrition, edema,• immunosuppressive therapy

• Management and Prophylaxis• high index of suspicion, prompt evaluation• early initiation of therapy• polyvalent neumococcal vaccine

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• Manifestations• Hyponatremia, hypokalemia, Hypocalcemia• Hypovolemic shock

• Cause • salt intake restriction• diuretic treatment• vomit, diarrhea, intestinal reabsorbtion• Loss of calcium binding protein

• Prophylaxis • Avoiding aggressive diuretic therapy• Inappropriate salt intake restriction

Electrolytes disorder and hypovolemia

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Hypercoagulability and thrombosis

Manifestations• thrombosis within kidney, extremities, brai

n and lungCause

• coagulation factors , , , , ↑, platelⅡ Ⅴ Ⅶ Ⅷ Ⅹet aggregation↑, antithrombin ↓Ⅲ

• Hyperlipidemia, diuretic and steroid therapy

prophylaxis• Avoiding puncture of deep veins• Prophylactic anticoagulation drugs

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Manifestations• Oliguria or anuria ， hypertension• Elevated serum Cr and BUN levels

Cause• Intravascular blood volume↓• Obstruction, crescent formation• Acute interstitial nephritis, drugs

Prophylaxis• Avoiding use of renal toxic drugs• Avoiding aggressive diuretic therapy

Acute renal failure

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Renal tubular function disorder

Manifestations• polyuria, nocturia, Glucosuria,• aminoaciduria, Fanconi syndrome

Cause• Progress of the glomerular disease• Persistent massive proteinuria

prophylaxis• avoiding excessive albumin transfusi

on

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Prognosis

• Relapse and resolve

• Prognosis is depend on

pathologic patterns

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Thank You