Nephrotic Syndrome
Department of Prdiatrics,Tongji Hospital
Tel,83662684
Nephrotic Syndrome
? Definition
? Etiology
? Pathology
? Pathophysiology
? Clinical Manifestation
? Laboratory Data
? Diagnosis
? Therapy and Prognosis
Male
4 years and 6
months old
Complaint of
edema and
oliguria
Definition,Nephrotic Criteria
? Massive proteinuria
? ISKDC,> 40mg/m2/hr
? CAN,>+++ trice/2w or >50-100mg/kg/24hr
? Mendoza,Urine Protein/Cr ≥ 2.0
? Hypoalbuminemia,< 30g/L
? Hyperlipidemia:Cholesterol> 5.72mmol/L
? Edema
Definition,Nephritic Criteria
? Hematuria,RBC ++( >10 /HP),trice/2w
? Hypertension:
? >130/90 mmHg in children over 7y
? > 120/80 mm Hg in 3-6y children
? > 110/70 mm Hg in < 3y children
? Azotemia:BUN>6.4mmol/L,Cr >133umol/L
? Hypocomplementemia,C3<0.8/L
Definition
? Nephritic Nephrosis,nephrotic
criteria with at least one nephritic
criteria
? Simple nephrosis,nephrotic
criteria without nephritic criteria
Etiology
? Congenital NS,rare
? Idiopathic NS,majority
? Secondary NS,many causes especially
in <3y or >13y patients
causes― DIAMOND
Secondary NS, DIAMOND
? Infection,APSGN,HBV,HIV,shunt nephropathy,reflux
nephropathy,leprosy,syphilis,schistosomiasis,hydatid disease
? Drug,Toxic,Allegy,mercury,snake venom,vaccine,
pellicillamine,Heroin,gold,NSAID,captopril,probenecid,volatile
hydrocarbons
? Neoplasma,Hodgkin’s disease,carcinoma ( renal cell,lung,
neuroblastoma,breast,and etc)
? Autoimmune or collagen-vascular diseases:
SLE,Hashimoto’s thyroiditis,EMC,HSP,Vasculitis
? Genetic Disease,Alport syn.,Fabry syn.,Nail-patella syn.,
Sickle cell disease,Amyloidosis,Congenital nephropathy
? Metabolic disease,Diabetes mellitus
? Others,Chronic transplant rejection,congenital nephrosclerosis
Pathology
? Primary NS,
– Minimal Change Nephropathy (MCN),80%
– Mesangial proliferative glomerulonephritis (MsPGN),
10-12%
– Focal segmental glomerulosclerosis (FSGS),5%
– Others,
Membranous Nephropathy (MN) ― most common in
adults
Membrane proliferative glomerulonephritis (MPGN),2-5%
Cresent glomerulonephritis,rare,Crescent glomeruli > 50%
? Secondary NS,dependent on causes,APSGN,MN,
FSGS,MsPGN or MPGN
Minimal Change Nephropathy
(MCN )
? Little or no microscopic abnormality
? Absence of immune complexes
? Effacement of epithelial foot process
? Occasionally mesangial hypercellurity
MCN,normal in LM
MCN,effacement of epithelial foot process in EM
Mesangial proliferative
glomerulonephritis (MsPGN)
? Mesangial proliferation and expansion
? IgG,C3 and sometimes IgA,IgM
deposits in mesangial stalk
? Electron-dense deposits in mesangial or
paramesangial areas
MsPGN,Mesangial proliferation and expansion
IgG and C3 deposits in mesangial
Mesangial proliferative
glomerulonephritis (MsPGN)
? Mesangial proliferation and expansion
? IgG,C3 and sometimes IgA,IgM
deposits in mesangial stalk
? Electron-dense deposits in mesangial or
paramesangial areas
Focal segmental glomerulosclerosis
(FSGS)
? Focal and segmental capillary collapse
and mesangial sclerosis
? Deposits of IgM or C3 in the glomeruli
? Loss of visceral epithelial cell podocytes,
duplication of the basal GBM
lamina,separation of epithelial cell from
GBM
Membranous Nephropathy (MN)
? Diffuse GBM thickening,characteristic
GBM spikes
? Subepithelial deposit of IgG and C3
Membrane proliferative
glomerulonephritis (MPGN)
? Mesangial proliferation and expansion
? Subendothelial mesangial interposition,
tram track apperance
? Mesangial and subendothelial deposits of
IgG and C3
Pathophysiology of
nephrotic syndrome
MCN,Involvement of
immune system
? No Ig or complement deposit
? Association between allegy and idiopathic NS
? Abnormalities of humural and cellular immunity,IgG↓,
IgA↓,CD4/CD8↓
? Relapse of NS triggered by a variety of minor infections
? Autologous remission after measles
? Induction of remission by corticosteroids and akylating
agents
MCN,pathogenesis of
proteinuria
? Lymphacyte → 29kd peptide → glomerular
polyanion↓→ proteinuria
? Con A → lymphacytes → 60-160kd GPF →
proteinuria
? lymphacytes → 13-18kd SIRS → proteinuria
GPF,glomerular permeability factor
SIRS,soluble immune response suppressor
MCN,pathogenesis of
edema
? FFNa↓,CH2O↓ ? Edema
? Proteinuria ? Na reabsorption in distal renal
tubules ?? Na and water retention ? Edema
? Hypoalbuminemia ?intravascular oncotic
pressure↓ (25mmHg→6-8mmHg) ?Fluid
extravasation?hypovolemia ?ADH ?and
aldosterone ??Water and salt retension ?
Edema
MCN,pathogenesis of
hypoalbuminemia
? Loss of protein from ultrafiltration
? Increased catabolism of protein in renal
tubules
? Loss from intestine proved by
51Chromium-albumin tracing
MCN,pathogenesis of
hyperlipidemia
Hypoalbuminemia → hypatic synthesis
of lipid↑→ hyperlipidemia
Clinical Manifestation
?Simple nephrosis,2--7y,massive edema in face
and paraorbital areas,ascites,pleural effusion,loss of
appetite,nausea and vomiting,inertia and lethargy
?Nephritic nephrosis,> 7y,moderate edema,
gross hematuria,hypertension
?Complications:
Complications (1)
?Infection,URI,peritonitis,cellulitis and etc
– IgG?,IgA?,Complement ?
– WBC function ?
– Lack of Zn and other trace elements
? Hypercoagulable state and thrombosis
– Higher concentration of Ⅴ,Ⅶ,Ⅷ,Ⅹ
– Lower level of anticoagulant substance:
antithrombinⅢ, protein S,protein C
– Overvigorous diuresis
– Higher blood viscosity,increased platelet aggregation
– Role of corticosteroids
Complications (2)
? Electrolyte imbalance,hyponatrimia,
hypokalemia,hypercalcemia
– Salt-depleted diet
– Overvigorous diuresis
– Extrarenal loss
– Protein-bound calcium loss from urine
– Steroids induced hypocalcemia
? ARF,pre-renal
? Hypovolemic shock
? Others,growth failure
Laboratory Data (1)
?ESR,simple nephrosis > 100mm/h,
nephritic nephrosis < 100mmHg
?Serum preotein electrophoresis,?2?,
??,?? in simple nephrosis but ?? in
nephritic Nephrosis
?Immunoglobulin,IgG?,IgA?,IgM?
– IgA>IgM,C3? ? nephritic nephrosis
– IgM>IgA,normal C3? simple nephrosis
Laboratory Data (2)
?Renal function,usually normal
?Urine protein pattern:
–simple nephrosis ? albumin
–nephritic nephrosis ? IgG,albumin
and others
?Ratio of UIgG/ U albumin
– simple nephrosis ? <1
– nephritic nephrosis ? >1
Diagnosis and differential
diagnosis
? Idiopathic or secondary
? MCN or non-MCN
importance of renal biopsy
Treatment of NS
? General principle
? Anticoagulation
? Corticosteroids
? Immunosuppressive agents
? Chinese traditional medicine
General principle
? Low salt diet (2g/d),appropriate
protein intake (2-3g/kg/d)
? Avoiding infection
? Diuresis,Thiazide –DHCT 2mg/kg/d
Antisterone 2-4mg/kg/d
Dextran 10-20ml/kg followed by
Lasix at 2mg/kg
Anticoagulation
? Dipyridamole,5mg/kg/d
? Heparin,0.5-1mg/kg/d× 7-10d
? Warfarin,initial dose,2.5mgTid× 3-5d
Subsequent dose,2.5-10mg/d
based on PT
Corticosteroids
? Short course,2mg/kg/d→ pro(-) 1.5mg/kg/qod× 4w →
no taper,Course <8w,Relapse rate (1y)= 81%
? Standard course,2mg/kg/d× 4w → 2mg/kg/qod× 4w →
taper,Course < 6m,Relapse rate (1y)= 61%
? Long course,2mg/kg/d× 4-6w →
2mg/kg/qod× 4-6w → taper,Course < 9-12m,Relapse
rate (1y)= 31%
Steroids treatment response
? high response,4w→proteinuria( -)
? response,8w→proteinuria( -)
? partial response,8w→proteinuria(+/++)
? steroid dependent,responsive but require
high dose
? relapse,proteinuria(-)→proteinuria(++ or up)
? frequent relapse,relapse twice/6m or trice/1y
Side effect of steroids
? Growth failure
? Hypertension
? posterior sublenticular cataracts
? Osteoporotic bone disease
? Gastric ulcer→hematesis
Immunosuppressive
agents(1)
? CTX,2-2.5mg/kg/d× 8-12w,maxium
single dose 0.1,maxium cumulative 200-
250mg/kg
? Chlorambucil,0.2mg/kg/d× 8-12w,
maxium single dose 6mg,maxium
cumulative dose 12-16mg/kg
? Cyclosporin A,5-6mg/kg/d× 2-6m,
keep blood concentration at 50-150ng/ml
Immunosuppressive
agents(2)
? Vincristine,0.075mg/kg weekly,maxium
single dose<2mg
? 6-TG(6-thioguanine),2mg/kg/d× 8w,
maxium single dose<75mg
? nitrogen mustard,0.1mg/kg/d× 4d,
may be repeated 1 month later
? azathioprine,1-2mg/kg/d× 8-12w
New immunosuppressive agents
? Mycophenolate mofetil acid (MMF),
Cellcept
? FK506,Prograf,Tacrolimus
? Rapamycin,Sirulimus
? Simulect,basiliximab,daclizumab
? FYT-720,Gusperimus,SDS-RAD
Pulse therapy
Methylprednisolone,15-30mg/kg× 3d
Indication,refractory nephrosis,
Lupus
RPGN,cocktail protocol
FSGS,Mendoza protocol
MN,Ponticelli protocol
Prognosis
? Generally good,especially for
MCN
? MsPGN,good or poor
? FSGS,50% to ESRF
Male
4 years and 6
months old
Complaint of
edema and
oliguria
Department of Prdiatrics,Tongji Hospital
Tel,83662684
Nephrotic Syndrome
? Definition
? Etiology
? Pathology
? Pathophysiology
? Clinical Manifestation
? Laboratory Data
? Diagnosis
? Therapy and Prognosis
Male
4 years and 6
months old
Complaint of
edema and
oliguria
Definition,Nephrotic Criteria
? Massive proteinuria
? ISKDC,> 40mg/m2/hr
? CAN,>+++ trice/2w or >50-100mg/kg/24hr
? Mendoza,Urine Protein/Cr ≥ 2.0
? Hypoalbuminemia,< 30g/L
? Hyperlipidemia:Cholesterol> 5.72mmol/L
? Edema
Definition,Nephritic Criteria
? Hematuria,RBC ++( >10 /HP),trice/2w
? Hypertension:
? >130/90 mmHg in children over 7y
? > 120/80 mm Hg in 3-6y children
? > 110/70 mm Hg in < 3y children
? Azotemia:BUN>6.4mmol/L,Cr >133umol/L
? Hypocomplementemia,C3<0.8/L
Definition
? Nephritic Nephrosis,nephrotic
criteria with at least one nephritic
criteria
? Simple nephrosis,nephrotic
criteria without nephritic criteria
Etiology
? Congenital NS,rare
? Idiopathic NS,majority
? Secondary NS,many causes especially
in <3y or >13y patients
causes― DIAMOND
Secondary NS, DIAMOND
? Infection,APSGN,HBV,HIV,shunt nephropathy,reflux
nephropathy,leprosy,syphilis,schistosomiasis,hydatid disease
? Drug,Toxic,Allegy,mercury,snake venom,vaccine,
pellicillamine,Heroin,gold,NSAID,captopril,probenecid,volatile
hydrocarbons
? Neoplasma,Hodgkin’s disease,carcinoma ( renal cell,lung,
neuroblastoma,breast,and etc)
? Autoimmune or collagen-vascular diseases:
SLE,Hashimoto’s thyroiditis,EMC,HSP,Vasculitis
? Genetic Disease,Alport syn.,Fabry syn.,Nail-patella syn.,
Sickle cell disease,Amyloidosis,Congenital nephropathy
? Metabolic disease,Diabetes mellitus
? Others,Chronic transplant rejection,congenital nephrosclerosis
Pathology
? Primary NS,
– Minimal Change Nephropathy (MCN),80%
– Mesangial proliferative glomerulonephritis (MsPGN),
10-12%
– Focal segmental glomerulosclerosis (FSGS),5%
– Others,
Membranous Nephropathy (MN) ― most common in
adults
Membrane proliferative glomerulonephritis (MPGN),2-5%
Cresent glomerulonephritis,rare,Crescent glomeruli > 50%
? Secondary NS,dependent on causes,APSGN,MN,
FSGS,MsPGN or MPGN
Minimal Change Nephropathy
(MCN )
? Little or no microscopic abnormality
? Absence of immune complexes
? Effacement of epithelial foot process
? Occasionally mesangial hypercellurity
MCN,normal in LM
MCN,effacement of epithelial foot process in EM
Mesangial proliferative
glomerulonephritis (MsPGN)
? Mesangial proliferation and expansion
? IgG,C3 and sometimes IgA,IgM
deposits in mesangial stalk
? Electron-dense deposits in mesangial or
paramesangial areas
MsPGN,Mesangial proliferation and expansion
IgG and C3 deposits in mesangial
Mesangial proliferative
glomerulonephritis (MsPGN)
? Mesangial proliferation and expansion
? IgG,C3 and sometimes IgA,IgM
deposits in mesangial stalk
? Electron-dense deposits in mesangial or
paramesangial areas
Focal segmental glomerulosclerosis
(FSGS)
? Focal and segmental capillary collapse
and mesangial sclerosis
? Deposits of IgM or C3 in the glomeruli
? Loss of visceral epithelial cell podocytes,
duplication of the basal GBM
lamina,separation of epithelial cell from
GBM
Membranous Nephropathy (MN)
? Diffuse GBM thickening,characteristic
GBM spikes
? Subepithelial deposit of IgG and C3
Membrane proliferative
glomerulonephritis (MPGN)
? Mesangial proliferation and expansion
? Subendothelial mesangial interposition,
tram track apperance
? Mesangial and subendothelial deposits of
IgG and C3
Pathophysiology of
nephrotic syndrome
MCN,Involvement of
immune system
? No Ig or complement deposit
? Association between allegy and idiopathic NS
? Abnormalities of humural and cellular immunity,IgG↓,
IgA↓,CD4/CD8↓
? Relapse of NS triggered by a variety of minor infections
? Autologous remission after measles
? Induction of remission by corticosteroids and akylating
agents
MCN,pathogenesis of
proteinuria
? Lymphacyte → 29kd peptide → glomerular
polyanion↓→ proteinuria
? Con A → lymphacytes → 60-160kd GPF →
proteinuria
? lymphacytes → 13-18kd SIRS → proteinuria
GPF,glomerular permeability factor
SIRS,soluble immune response suppressor
MCN,pathogenesis of
edema
? FFNa↓,CH2O↓ ? Edema
? Proteinuria ? Na reabsorption in distal renal
tubules ?? Na and water retention ? Edema
? Hypoalbuminemia ?intravascular oncotic
pressure↓ (25mmHg→6-8mmHg) ?Fluid
extravasation?hypovolemia ?ADH ?and
aldosterone ??Water and salt retension ?
Edema
MCN,pathogenesis of
hypoalbuminemia
? Loss of protein from ultrafiltration
? Increased catabolism of protein in renal
tubules
? Loss from intestine proved by
51Chromium-albumin tracing
MCN,pathogenesis of
hyperlipidemia
Hypoalbuminemia → hypatic synthesis
of lipid↑→ hyperlipidemia
Clinical Manifestation
?Simple nephrosis,2--7y,massive edema in face
and paraorbital areas,ascites,pleural effusion,loss of
appetite,nausea and vomiting,inertia and lethargy
?Nephritic nephrosis,> 7y,moderate edema,
gross hematuria,hypertension
?Complications:
Complications (1)
?Infection,URI,peritonitis,cellulitis and etc
– IgG?,IgA?,Complement ?
– WBC function ?
– Lack of Zn and other trace elements
? Hypercoagulable state and thrombosis
– Higher concentration of Ⅴ,Ⅶ,Ⅷ,Ⅹ
– Lower level of anticoagulant substance:
antithrombinⅢ, protein S,protein C
– Overvigorous diuresis
– Higher blood viscosity,increased platelet aggregation
– Role of corticosteroids
Complications (2)
? Electrolyte imbalance,hyponatrimia,
hypokalemia,hypercalcemia
– Salt-depleted diet
– Overvigorous diuresis
– Extrarenal loss
– Protein-bound calcium loss from urine
– Steroids induced hypocalcemia
? ARF,pre-renal
? Hypovolemic shock
? Others,growth failure
Laboratory Data (1)
?ESR,simple nephrosis > 100mm/h,
nephritic nephrosis < 100mmHg
?Serum preotein electrophoresis,?2?,
??,?? in simple nephrosis but ?? in
nephritic Nephrosis
?Immunoglobulin,IgG?,IgA?,IgM?
– IgA>IgM,C3? ? nephritic nephrosis
– IgM>IgA,normal C3? simple nephrosis
Laboratory Data (2)
?Renal function,usually normal
?Urine protein pattern:
–simple nephrosis ? albumin
–nephritic nephrosis ? IgG,albumin
and others
?Ratio of UIgG/ U albumin
– simple nephrosis ? <1
– nephritic nephrosis ? >1
Diagnosis and differential
diagnosis
? Idiopathic or secondary
? MCN or non-MCN
importance of renal biopsy
Treatment of NS
? General principle
? Anticoagulation
? Corticosteroids
? Immunosuppressive agents
? Chinese traditional medicine
General principle
? Low salt diet (2g/d),appropriate
protein intake (2-3g/kg/d)
? Avoiding infection
? Diuresis,Thiazide –DHCT 2mg/kg/d
Antisterone 2-4mg/kg/d
Dextran 10-20ml/kg followed by
Lasix at 2mg/kg
Anticoagulation
? Dipyridamole,5mg/kg/d
? Heparin,0.5-1mg/kg/d× 7-10d
? Warfarin,initial dose,2.5mgTid× 3-5d
Subsequent dose,2.5-10mg/d
based on PT
Corticosteroids
? Short course,2mg/kg/d→ pro(-) 1.5mg/kg/qod× 4w →
no taper,Course <8w,Relapse rate (1y)= 81%
? Standard course,2mg/kg/d× 4w → 2mg/kg/qod× 4w →
taper,Course < 6m,Relapse rate (1y)= 61%
? Long course,2mg/kg/d× 4-6w →
2mg/kg/qod× 4-6w → taper,Course < 9-12m,Relapse
rate (1y)= 31%
Steroids treatment response
? high response,4w→proteinuria( -)
? response,8w→proteinuria( -)
? partial response,8w→proteinuria(+/++)
? steroid dependent,responsive but require
high dose
? relapse,proteinuria(-)→proteinuria(++ or up)
? frequent relapse,relapse twice/6m or trice/1y
Side effect of steroids
? Growth failure
? Hypertension
? posterior sublenticular cataracts
? Osteoporotic bone disease
? Gastric ulcer→hematesis
Immunosuppressive
agents(1)
? CTX,2-2.5mg/kg/d× 8-12w,maxium
single dose 0.1,maxium cumulative 200-
250mg/kg
? Chlorambucil,0.2mg/kg/d× 8-12w,
maxium single dose 6mg,maxium
cumulative dose 12-16mg/kg
? Cyclosporin A,5-6mg/kg/d× 2-6m,
keep blood concentration at 50-150ng/ml
Immunosuppressive
agents(2)
? Vincristine,0.075mg/kg weekly,maxium
single dose<2mg
? 6-TG(6-thioguanine),2mg/kg/d× 8w,
maxium single dose<75mg
? nitrogen mustard,0.1mg/kg/d× 4d,
may be repeated 1 month later
? azathioprine,1-2mg/kg/d× 8-12w
New immunosuppressive agents
? Mycophenolate mofetil acid (MMF),
Cellcept
? FK506,Prograf,Tacrolimus
? Rapamycin,Sirulimus
? Simulect,basiliximab,daclizumab
? FYT-720,Gusperimus,SDS-RAD
Pulse therapy
Methylprednisolone,15-30mg/kg× 3d
Indication,refractory nephrosis,
Lupus
RPGN,cocktail protocol
FSGS,Mendoza protocol
MN,Ponticelli protocol
Prognosis
? Generally good,especially for
MCN
? MsPGN,good or poor
? FSGS,50% to ESRF
Male
4 years and 6
months old
Complaint of
edema and
oliguria
