Nephrotic Syndrome(NS)

（肾病综合征）

Department of pediatrics
The third affiliated hospital
of zhengzhou university
郑大三附院 儿科
杜开先
Email: dukaixian@126.com
Telephone: 66903476
 Purpose and requirement
1.To understand classification,
path-physiology and pathogenesis
of nephrotic syndrome
2.To master the differential diagnosis
between the simple nephrotic syndrome
and nephritic type NS
 Purpose and requirement
3. To understand the complication of
nephrotic syndrome
4. To master the principle of treatment
and how to treatment nephrotic
syndrome with corticosteroid and
other immunosuppressive drugs
 Teaching emphases
1. How to differentiate AGN from
Primary nephrotic syndrome,
2. The differential diagnosis between
the simple and nephritic NS
3. The manifestations and treatment
of NS
4. How to treat nephrotic syndrome with
corticosteroid
 Introduction(1)
1.Nephrotic syndrome (NS) or Nephrosis is a
condition that is often caused by any of a
group of diseases that damage the kidneys
filtering system, the glomeruli.
The condition lead to hypoalbuminemia (low
level of albumin in the blood) ,Edema
(swelling)and Hypercholesterolemia (high
level of cholesterol in the blood) .
 Introduction(2)

2. An increased glomerular permeability

resulting in proteinuria is the primary
renal abnormality in NS
3. It is a common disease among chinese
children and more in boys than in girls
(2-4:1).Mean age at onset is 2 to 7 yr
average at 2.5years of age.
 Etiology
NS can be divided into three groups:
Primary (Idiopathic):
85 ~ 90%,associate with immune
disorder, but unclear.
Secondary:
10 ~ 15%,due to infections,drugs or
toxins, autoimmunous diseases ,
tomors.
Infantile (congenital ): rare
 Pathology
Most (90%)children with primary nephrotic
syndrome have some form of idiopathic
nephrotic syndrome:
1.Minimal-change diseases (MCD): 85%
the glomeruli appear normal. the epithelial
cell foot processes fused.
More than 95% of children with MCD, and
better responding to corticosteriod therapy.
Minimal-change disease: the glomeruli
appear normal. the epithelial cell foot
processes fused
 Pathology
2. Focal segmental glomerulo-
sclerosis (FSGS):
10%,sclerosis and hyalinosis
involving a portion of glomerular
tuft, even only of the glomeruli,
accompanied tubular atrophy. IgM
and C3(complement) within
sclerotic areas.
Focal segmental glomerulo-sclerosis
 Pathology
3. membranoproliferative
glomerulonephritis (MPGN):
 5% diffuse proliferation of

mesangial cells and matrix,

electronic density deposits and
C3 desposit in mesangial and
GBM.
 系膜增生性肾小球肾炎 (HE× 400)
membranoproliferative glomerulonephritis
 Pathology
4. Membranous
Glomerulonephritis (MGN): rare
GBM (glomerular basement
membranes) thicker,
IgG and C3 deposits.
 Pathophysiology(1)
1.Proteinuria:
The underlying pathogenetic abnormality
in NS is proteinuria, which increase in
glomerular capillary wall permeability.
Underlying defect is thought to be caused
by the loss of charge selectivity of the
glomerular basement membrane, which
permits negatively charged proteins,
primarily albumin to pass easily through
the capillary walls into the urine.
 Pathophysiology(2)
2.Hypoalbuminemia
Excessive urinary loss of protein
and catabolism by the kidney of
circulating albumin leads to a
decrease in serum protein .
Hypoproteinemia is fundamentally
a “hypoabluminemia”.
 Pathophysiology(3)
3. Edema
(1) The colloidal osmotic pressure is
reduced because of the amount
of serum albumin.
(2) The renin-angiotensin system and
the secretion of antidiuretic
hormone and aldosterone is increased
 Pathophysiology(4)
4. Hyperlipidemia
(1).The hypoproteinemia stimulates
generalized protein synthesis in
the liver including the lipoproteins;
(2). Lipid catabolism is diminished,
pertaining to reduced plasma
levels of lipoprotein lipase.
Sequence of Events in Nephrotic Syndrome
Pathophysiology Clinical Manifestations
Glomerular injury
Increased permeability of Heavy Proteinuria
glomerular basement
membrane Microhematuria(occasional)
Albuminurin
Hypoproteinemia
Decreased serum albumin Hypercholestrolemia
Decreased plasma oncotic pressure

Decreased peripheral Increased renal Urinary sodium

capillary return Na reabsorbption
Edema(Periorbital,
Increased interstitial fluid peripheral, ascites)
 Clinical manifestations(1)
1. Onset is insidious.
2. Edema is often the presenting symptom.
Edema may be minimal or massive, and
is usually first apparent around the eyes.
Depressed edema may occurs in areas of
the body, such as the hands, ankles, feet,
and genitalia. Severe edema may give
rise to ascites and/or pleural effusions.
Anasarca of NS
Ascites of NS
Depressed edema of NS
Severe swelling of the
ankles in nephrotic
syndrome
 Clinical manifestations(2)
3. Decreased urine output
4. General condition:
pallor, irritability, lethargy, fatigue.
5. Gastrointestinal disturbances:
Vomiting, diarrhea, anorexia.
 Clinical Manifestations (summary)
Four character of clinical manifestations
•Heavy Proteinuria ： urine protein +++ ~ ++++, 24 hrs
urine protein is more than 0.1g/kg.
•Hypoalbuminaemia: (low level of albumin in the blood)
albumin concentration less than 30 g/L ;
•Hypercholestrolemia: due to hypoalbuminaemia, but detail is
not clear.
•Severe Edema : Edema usually begin around eyes and face,
severe in morning and decrease in afternoon.With the
developing of the edema, ankles swelling, swelling foot,
swollen abdomen might occur. even entire body swelling.
 Laboratory tests(1)
1.Urinalysis
Protein ﹢﹢﹢or greater,
24 hour urine protein:
frequently greater than
0.05-0.1g/kg per day;
Hematuria:
absent or transient.
 Laboratory tests(2)
2.Blood Examination
Total protein: decreased
Albumin: less than 3g/dl;
Cholesterol: greater than 5.7mmol/L
Erythrocyte sedimentation rate (ESR):
accelerated
C3 normal
Different level of azotemia
 Laboratory tests(3)
3. Renal Biopsy
Renal biopsy is indicated if patient
is steroid resistant (has failed to
achieve remission after 28 days of
steroid therapy) or relapse and frequently
relapse or nephritic Type NS
 Diagnosis
Have the following condition
(1) Massive Proteinuria
UP≥ +++ ； or 〉 50mg/kg/d
(2) Hypoproteinemia
Albumin: less than 30g/L
(3) Edema
(4) Hyperlipemia
Cholesterol ＞ 5.7mmol/L
 Differential diagnosis

1. Simple NS and Nephritic NS

2. Acute Glomerulonephritis
and Nephrotic Syndrome
 1.Simple NS and Nephritic NS

Simple NS Nephritic NS

Pathol MCD non-MCD

clinic Depressed edema simple NS plus:
Massive proteinuria ① Persistent
hematuria ，
Hypoalbuminemia RBC>10/HP
Hyperlipemia ② Azotemia
③ Hypertension
④ persistent low
complement
 2.Acute Glomerulonephritis
and Nephrotic Syndrome
Assessment Factors AGN NS
Cause Immune reaction to Idiopathic; possibly
group A beta hemolytic a hypersensitivity
streptococcal infection reaction
Onset Abrupt Insidious
Hematuria Profuse Rare
Edema Mild Extreme
Hypertension Marked Mild
Hyperlipemia Rare or Mild Marked
Peak Age Incident 5-10 year 2-3 year
 Acute Glomerulonephritis
and Nephrotic Syndrome
Interventions Bed rest for Administration
3-4 weeks, of prednisone,
Antihypertensives Possibly diuretic
as needs; supplements
Symptomatic therapy
for congestive
heart fature
Diet Normal for age High-protein, low-salt
Prevention Prevention or thorough
treatment or group A None known
beta streptococcal infections
 Complication(1)

1.Infections major complication

reason:
① Decreased immunoglobulin levels
② The edema fluid acting as a culture
medium
③ Decreased bactericidal activity of
the leukocytes
④ Immunosuppressive therapy
 Complication(2)
Common sits infections:
Respiratory tract
Pneumonia
Sepsis
Cellulitis
Urinary tract infection (UTI)
Primary peritonitis
 Complication(3)
2.Hypercoagulation and Thrombosis
Reason:
(1) Elevated plasma levels of certain
coagulation factors
(2) Inhibitors of fibrinolysis
(3) Decreased plasma level of
anti-thrombin Ⅲ
(4) Elevated viscosity due to
hyperlipemia
(5) Increased platelet aggregation
 Complication(4)
3. Acute Renal Failure
Manifestation:
Oliguria (urine output less than
0.5-1ml/kg/hr), hematuria, headache,
edema, severe hypertension,
lethargy,
nausea and vomiting
 Complication(5)
4. Electrolyte Imbalance
The long-term use of diuretics,
steroids and diet limits can result
in electrolyts imbalance, including
hypokalemia, hyponatremia,
hypocalcemia.
5. Development Retardation
 Complications (summary)
Hypovolemic shock (shock due to low blood
volume):usually occur after diuresis,
Electrolyte disturbance : results from salt-free
foods,diuresis,diarrhea .
Acute renal failure (ARF):
majority associate with low blood volume.
Infections :respiratory infections,skin
infections, peritonitis.
 Complications (summary)
Thrombosis(Blood clot occurring in
a blood vessel) : Blood
abnormally overclots due to thick
blood, hypercholestrolemia . It is
easy to develop a blood clot in
the legs and renal veins.
Development Retardation
 Therapy
1. general therapy
(1) Rest
No restrictions are placed on the activity,
but some limitations are advisable
because of infection.
 Therapy
(2) Diet
.The diet should provide high quality of
protein ,low in fat , adequate carbon
-hydrate ,high vitamins , easy to digest
A diet with no added salt is advised if the
patient is edematous.
Fluid restriction is not usually required
unless the edema is severe
 Therapy
(3) Antibiotics
Antibodies can not be used for prevention, but for
treatment .
(4) Diuresis
Hydrochlorothiazide 1-3mg/kg/d
Spironolactone 1-2mg/kg/d
Furosemide 1-2mg/kg/d
Albumin 0.5-1g/kg/d
 Therapy
2. Corticosteroids:
Purpose:
to stop the loss of protein in the urine
(1) Short term 8W
Prednisone 2mg/kg/d (maximum daily
dose 60mg) divided into three doses
over the day for 4w , After 4w changed
to 1.5-2mg/kg/d taken every other day
as a single dose with breakfast .
Continues 4w later ---abrupt cease
(2) Middle 6-9M
Prednisone 2mg/kg/d (maximum daily
dose 60mg) divided into three doses
over the day , If urine protein become
negative within 4w; 2w after the urine
become protein free prednisone is
changed to 2mg/kg/d taken every other
day as a single dose with breakfast,
continued for 4w, later per 2-4w
subtract 2.5-5mg until cessation
Total duration :6 months
(3) Long term 9-12M
Prednisone 2mg/kg/d divided into three
doses over the day, If urine protein is not
become negative within 4w;continued the
doses until 2w after the urine become
protein free (not over 8w ), prednisone is
changed to 2mg/kg/d taken every other
day as a single dose with breakfast,
continued for 4w, later per 2-4w subtract
2.5-5mg until cessation
Total duration : 9 months
 Steroid response

Prednisone 2mg/kg/d (Maxdosage:60mg/d)

divided into three doses
(1) Steroid sensitive :
Achieving a remission within 28 days
of the start of prednisone therapy for
the initial presentation of NS
 Steroid response
(2) Steroid resistance :
Failure to achive response inspite of 8
weeks of prednisone therapy at
60mg/m2 per day
(3) Steroid dependent:
two consecutive relapses, occuring
during prednisone therapy, or within 14
days after its cessation
prednison
weight ）
treatment ： （ a sample of child of 15kg
Urine protein is negative Short-time protocol stops here,
(steroid sensitive) but long-time protocol begins to
10mg 30mg reduce dose by 2.5 ~ 5mg/time
t.i.d g.o.d every 2 ~4W.
weeks
Urine protein is positive(steroid
10mg 30mg
unsensitive)
t.i.d q.o.d
weeks
Urine protein is still positive
30mg （ teroid
resistance ）
q.o.d
weeks
add immunosuppression
( CTX 2mg/kg/d)
 Therapy
3. Immunosuppressive drugs
should be done in Frequent relapses , teroid
resistance, or steroid dependency.
(1) Cyclophosphamide ( cytoxan ,CTX )
oral: 2mg/kg/d,divice to 3 times , 8 ~ 12 weeks;
high dose: 10 ~ 12mg/kg/d + 5%Glucose 100
~200ml, ivdrip, successive 2 days, every 2 weeks.
(2) Cyclosporin A (CSA)
5mg/(kg.d)
Total duration: 3m-6m
 Therapy
4. Anti-Coagulation:
Heparin
1mg/kg/d ivgtt qd 2-4w
Urokinase
30000-60000U/d ivgtt qd 1-2w
Dipyridamole
5-10mg/kg/d tid po 6m
 Therapy
5. ACEI (angiotensin converting
enzyme inhibitors)
Captopril
0.3-0.5mg/kg/d tid po
Enalapril
0.08-0.1mg/kg/d bid po
 Prognosis
Most children with steroid-respond
nephrosis have repeated relapses until
the disease resolves spontaneously
toward the end of the 2nd decade of life.
It is important to indicate to the family
that the child will have no residual renal
dysfunction, that the disease is generally
not hereditary, and that the child( in the
absence of cyclophosphamide or
chlorambucil therapy) will remain fertile.
 Prognosis
To minimize the psychologic effects of
the nephrosis, it should be emphasized
that when in remission the child is
normal and may have unrestricted diet
and activity. While a child is in remission,
it is generally unnecessary to test the

urine for protein.