Dept.

of pediatrics, Tongji Hospital, HUST 1

Nephrotic Syndrome
In Children





Dept. of pediatrics, Tongji Hospital, HUST 2
Idiopathic nephrotic syndrome (INS)
Simple nephrosis nephritic nephrosis
Minimal change nephropathy (MCN)
Non-minimal change nephropathy (non-MCN)
Massive (heavyexcessive) proteinuria
Hypo-proteinemia hypo-albuminemia
Hyper-lipidemia hyper-cholesterolemia
Pitting edema non-pitting edema
Anasarca ascites pleural effusion
Corticosteroidprednisone methylprednisolone

Key words
Dept. of pediatrics, Tongji Hospital, HUST 3
Definition
Classification
Etiology
Pathology
Pathophysiology
Clinical Manifestation
Complication
Laboratory Data
Diagnosis
Treatment

Main Contents
Dept. of pediatrics, Tongji Hospital, HUST 4
Male patient,
4 years old,
Complaint of :
edema , oliguria
and proteinuria
for 7 days.
Dept. of pediatrics, Tongji Hospital, HUST 5
Nephrotic syndrome (NS) results from
increased permeability of glomerular basement
membrane (GBM) to plasma protein. It is a
syndrome characterized by massive proteinuria,
hypo-albuminemia, hyper-cholesterolemia
Hypercoagulable state and pitting edema.
(4-increase, 1-decrease).
Definition
Dept. of pediatrics, Tongji Hospital, HUST 6
Nephrotic Criteria
Massive proteinuria:
qualitative proteinuria: 3+ or 4+,
quantitative proteinuria : 50mg/kg.d
Hypo-albuminemia:
serum albumin : < 30g/L
Hyper-cholesterolemia:
serum cholesterol : > 5.7mmol/L
Hypercoagulable state ND
Edema:pitting edema in different degree

Dept. of pediatrics, Tongji Hospital, HUST 7
Nephritic Criteria
Hematuria: RBC in urine: 2+ (10 /HPF)
Hypertension:
130/90 mmHg in school-age children
120/80 mmHg in preschool-age children
110/70 mmHg in infant and toddlers children
Azotemiarenal insufficiency:
Increased level of serum BUN Cr
Hypo-complementemia:
Decreased level of serum c3
Dept. of pediatrics, Tongji Hospital, HUST 8


23RBC10/HP

120/80mmHg
130/90mmHg

(C
3
)
NS (Nephritic-type NS)
Dept. of pediatrics, Tongji Hospital, HUST 9
Clinical Classification of NS
Simple nephrosis: 80%
Only nephrotic criteria (4-increase, 1-decrease)
without nephritic criteria.
Nephritic nephrosis: 20%
Besides nephrotic criteria with at least
one or more nephritic criteria.

Dept. of pediatrics, Tongji Hospital, HUST 10
Etiology
Idiopathic NS (INS): majority
The cause is still unclear up to now. Recent 10 years ,
increasing evidence has suggested that INS may
result from a primary disorder of T cell function.
Accounting for 90% of NS in child. mainly discussed.
Secondary NS:
NS resulted from systemic diseases, such as anaphylactoid
purpura , systemic lupus erythematosus, HBV infection.
Congenital NS: rare



Dept. of pediatrics, Tongji Hospital, HUST 11
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: Hodgkins disease, carcinoma ( renal cell, lung,
neuroblastoma, breast, and etc)
Autoimmune or collagen-vascular diseases:
SLE, Hashimotos 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

Dept. of pediatrics, Tongji Hospital, HUST 12
(1) Minimal Change Nephropathy (MCN): 80%
The glomeruli appear normal basically, the foot process of
epithelial (podocyte) appears fused .
(2) NonMCN 20%
Mesangial proliferative glomerulonephritis
(MsPGN): about 10%
Focal segmental glomerulosclerosis (FSGS): 5%
Membranous Nephropathy (MN) : 2%
Membrane proliferative glomerulonephritis
(MPGN) : 1%
Others rareCresent glomerulonephritis
Pathology

Dept. of pediatrics, Tongji Hospital, HUST 13
Pathology: Minimal Change Nephropathy
Little or no lesion
under light microscopy (LM)
Absence of immune complex
under fluorescent microscopy (FM)
Fusion of foot process of epithelial
under electric microscopy (EM)


Dept. of pediatrics, Tongji Hospital, HUST 14
MCN: normal glomerulus in LM
Dept. of pediatrics, Tongji Hospital, HUST 15
Dept. of pediatrics, Tongji Hospital, HUST 16
MCN: fusion of foot process of epithelial in EM
Dept. of pediatrics, Tongji Hospital, HUST 17
MsPGN: Mesangial proliferation and expansion
IgG and C3 deposits in mesangial
Dept. of pediatrics, Tongji Hospital, HUST 18
2.INS



INS
Dept. of pediatrics, Tongji Hospital, HUST 19
Pathophysiology : pathogenesis of proteinuria
Dept. of pediatrics, Tongji Hospital, HUST 20
Pathophysiology : pathogenesis of proteinuria
Massive proteinuria is the most important
characteristics of NS.
Protein loss from urine exceeds 50mg/kg.d
generally and it is composed primarily of
albumin in NS .
NS results from increased permeability of
glomerular basement membrane (GBM)
to plasma protein.

Dept. of pediatrics, Tongji Hospital, HUST 21
Pathophysiology : pathogenesis of proteinuria
The mechanism of proteinuria may be related
to 2 aspects:
Molecular barrier injury: holes on GBM become
larger, plasma protein can pass through the GBM
into the urine ;
Charge barrier injury : loss of negative charge
(glycoprotein) within GBM, plasma protein
(with negative charge) can pass through the GBM
into the urine.

Dept. of pediatrics, Tongji Hospital, HUST 22
Pathophysiology : pathogenesis of proteinuria
Lymphocytes29kd peptide glomerular
negtive charge ( polyanion ) proteinuria
lymphocytes 60160kd GPF proteinuria
lymphocytes 1318kd SIRS proteinuria

GPF: glomerular permeability factor
SIRS: soluble immune response suppressor
MCN may be associated with a primary
disorder of Tcell lymphocyte function.
Dept. of pediatrics, Tongji Hospital, HUST 23
Pathophysiology :
pathogenesis of proteinuria
If the damage of glomeruli is mild and the permeability
is not so high , only lower molecular weight protein (
such as albumin, transferrin) can pass through the
GBM, which is called selective proteinuria;

If the damage of glomeruli is severe , both small and
large proteinssuch as IgG, IgAcan all pass through
the GBM, which is called non-selective proteinuria.




Dept. of pediatrics, Tongji Hospital, HUST 24
Pathophysiology :
pathogenesis of hypoalbuminemia
Loss of plasma protein from urine
Loss of extrarenal , such as from intestine
Increased catabolism of protein in renal tubules
Dept. of pediatrics, Tongji Hospital, HUST 25
Pathophysiology :
pathogenesis of hyperlipidemia
Hypoalbuminemia synthesis of generalized
protein ( including lipoprotein ) and lipid in
the liver hyperlipidemia
Lipoprotein levels and all serum lipid
(including cholesterol , triglycerides ) are
increased
Dept. of pediatrics, Tongji Hospital, HUST 26
Higher concentration of I, ,,,,
Lower level of anticoagulant substance:
antithrombin protein S, protein C
Overvigorous diuresis, blood inspissation
Higher blood viscosity
Increased platelet aggregation
Role of corticosteroid
Pathophysiology :
pathogenesis of Hypercoagulable state
Dept. of pediatrics, Tongji Hospital, HUST 27
Pathophysiology :
pathogenesis of edema
Hypoalbuminemia plasma colloid osmotic pressure (
25mmHg68mmHg )
fluid extravasation (intravascularinterstitial)
Edema
Intravascular volume antidiuretic hormone (ADH )
and aldosterone(ALD) water and sodium
retension Edema
Intravascular volume glomerular filtration rate
(GFR) water and sodium retension Edema

Dept. of pediatrics, Tongji Hospital, HUST 28
INS









ADHRAAS

INS
GFR

Dept. of pediatrics, Tongji Hospital, HUST 29
Clinical Manifestation
Non-specific symptoms:
fatigueinertia and lethargy
loss of appetite, nausea and vomiting,
abdominal pain , diarrhea
body weight increase, urine output decrease
Pitting edema in different degree :
Local edema: edema in face , around eyes,
in lower extremities.
Generalized edema (anasarca): edema in
penis and scrotum.
Celom effusionascites, pleural effusion


,



Dept. of pediatrics, Tongji Hospital, HUST 30
Ascites and abdomen distention
Edema in scrotum
and penis
Dept. of pediatrics, Tongji Hospital, HUST 31
Clinical Manifestation
Edema in scrotum and penis
Dept. of pediatrics, Tongji Hospital, HUST 32
Clinical Manifestation
Pitting edema and abdomen distention
Dept. of pediatrics, Tongji Hospital, HUST 33
Complications
Infection: URI, UTI, peritonitis, cellulitis
IgG, IgA, Complement
WBC function
Lack of Zinc and other trace elements
thrombosis
Higher concentration of ,,,,,
Lower level of anticoagulant substance: antithrombin
Overvigorous diuresis, blood inspissation
Higher blood viscosity
Increased platelet aggregation
Role of corticosteroid
Inducementinfection and vascular puncture

Dept. of pediatrics, Tongji Hospital, HUST 34
Complications
Electrolyte imbalance:
hyponatrimia, hypokalemia, hypocalcemia
Lower salt diet
Overvigorous(excessive) diuresis
Extra-renal loss
Steroid induced hypocalcemia
ARF: pre-renal and renal
Hypovolemic shock
Others: growth retardation, malnutrition,
adrenal cortical insufficiency

Dept. of pediatrics, Tongji Hospital, HUST 35
Laboratory Data
Qualitative proteinuria: 3+ or 4+
24-hour urine total protein
(quantitative proteinuria ): 50mg/kg.d
Urine protein pattern:
simple nephrosis albumin selective pro.
nephritic nephrosis albumin, IgG , IgA and
other proteins non-selective proteinuria.




Dept. of pediatrics, Tongji Hospital, HUST 36
Laboratory Data
Serum biochemistry:
TP , ALB , CHOL
Serum electrolyte:
Natrium , Kalium , Calcium
Coagulable state PT, KPTT , FIB, D-D
Renal function:BUN, Crusually normal
Serum immunoglobulin and C3:
IgGIgA IgMIgE C3, N,
Serum preotein electrophoresis
r, a2,






Dept. of pediatrics, Tongji Hospital, HUST 37
Diagnosis and differential diagnosis
How can we recognize a child who has NS?
Simple or nephritic NS?
Refractory NS
Idiopathic or secondary NS?
MCN or non-MCN?
deductionrenal biopsy
Complication

The pathway of diagnosis
Dept. of pediatrics, Tongji Hospital, HUST 38
Treatment
General (non-specific ) and Symptomatic
therapy
Anticoagulation therapy
Corticosteroid therapy
Immunosuppressive agent therapy
Chinese traditional medicine therapy


Dept. of pediatrics, Tongji Hospital, HUST 39
General therapy

Activity: usually no restriction , except
massive edemaheavy hypertension and infection.
Diet: Lower salt diet (2g/d) only during period of edema,
normal or appropriate protein intake (23g/kg.d).
Avoiding infection: very important.
Diuresis: Hydrochlorothiazide (HCT) 2mg/kg.d
Antisterone 24mg/kg.d
Dextran 1015ml/kg , after 3060m,
followed by Furosemide (Lasix) at 2mg/kg .
Dept. of pediatrics, Tongji Hospital, HUST 40
Anticoagulation therapy
Dipyridamole: 5mg/kg.d
Heparin : 1.01.5mg/kg.d , 710d
Warfarin: Initial dose: 2.5mg , Tid35d
Subsequent dosage : 2.55mg/d
Regulation of dosage
according to coagulable state.
Dept. of pediatrics, Tongji Hospital, HUST 41
Corticosteroidprednisone therapy
Short course: 2mg/kg.d pro(-) , 2mg/kg.qod4w
no taper , termination, total course : 812 w,
Relapse rate (1y) 81%
Medium (Standard) course: 2mg/kg.d4w
2mg/kg.qod4w taper, total Course : about 6 m,
Relapse rate (1y) 61%
Long course: 2mg/kg.d46w
2mg/kg.qod46w taper, total Course: 912m,
Relapse rate (1y) 31%





Induction phase and maintanence phase
Dept. of pediatrics, Tongji Hospital, HUST 42
Response to Steroid therapy
steroid-responsive NS : 8wproteinuria (-)
steroid-dependent NS : steroid-responsive ,
but require maintenance of prednisone
at high dosage .
steroid-resistant NS : 8wproteinuria remains
(+++/++++)
relapse: proteinuria (-)(++ or up) for over 2w
frequent relapse: relapse twice/6m or trice/1y.
According to response to prednisone therapy
Dept. of pediatrics, Tongji Hospital, HUST 43

(1)INS (steroid-responsive NS)
8
(2)INS (steroid-resistant NS)
8
(3)INS (steroid-dependent NS)
1
2
(4)relapsefrequent relapse
2
213
INS
INS:
Dept. of pediatrics, Tongji Hospital, HUST 44
Immunosuppressive agent therapy
Frequent relapse
Steroid dependent
Steroid resistant
Severe steroid toxicity

Indication:
Dept. of pediatrics, Tongji Hospital, HUST 45
Immunosuppressive agent therapy
CyclophosphamideCTX: 22.5mg/kg.d
812w, total maxium cumulative dose :
200mg/kg , oral administration
Chlorambucil: 0.2mg/kg.d812w, total
maxium cumulative dose1216mg/kg
Cyclosporin A: 56mg/kg.d 6m or more, keep
blood concentration between 50150ng/ml
azathioprine: 12mg/kg.d 812w
Mycophenolate mofetil (MMF):
Dept. of pediatrics, Tongji Hospital, HUST 46
Pulse therapy
Methylprednisolone(MP):
1530mg/kg3d
Cyclophosphamide(CTX):
500750mg/once/mfor 6m or more,
total cumulative dose 150200mg/kg
Indication:
Refractory nephrosis,
Lupus nephritis,
purpura nephritis
RPGN
Others

Dept. of pediatrics, Tongji Hospital, HUST 47
1.What is nephrotic syndrome
2.What are the main clinical types of INS ?
3.What is the diagnostic criteria of INS
4.What are the pathological types of INS ?
5.What are the common complications of INS
6.How do you treat INS (general principles)
7.How do you evaluate the response of steroid therapy
Questions