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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 ))
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
