Mohammad Ali Al-shehri
Supervised by :
Nephrotic Syndrome..Ὴ(NS) Nephrotic Syndrome..Ὴ(NS)
Definition of NS
Etiology of NS
Pathology of NS
Pathophysiology of NS
Clinical Manifestation of NS
Nephrotic syndrome Nephrotic syndrome
Nephrotic syndrome (NS) results from
increased permeability of Glomeulrar
basement membrane ( GBM ) to plasma
It is clinical and laboratory syndrome
characterized by massive proteinuria, which
lead to hypoproteinemia ( hypo-
albuminemia), hyperlipidemia and pitting
qualitative proteinuria: 3+ or 4+,
quantitative proteinuria : more than 40
mg/m2/hr in children (selective).
total plasma proteins < 5.5g/dl and serum
albumin : < 2.5g/dl.
serum cholesterol : > 5.7mmol/L
*Edema : pitting edema in different degree
Nephr i tic Criteria
-Hematuria: RBC in urine (gross hematuria)
ᶟ130/90 mmHg in school-age children
ᶟ120/80 mmHg in preschool-age children
ᶟ110/70 mmHg in infant and toddlerᾼs children
-Azotemia （renal insufficiency ）:
Increased level of serum BUN 、Cr
Decreased level of serum c3
A-Primary 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 Tᾶ cell function.
Accounting for 90% of NS in child. mainly discussed .
NS resulted from systemic diseases, such as
anaphylactoid purpura , systemic lupus
erythematosus, HBV infection.
C-Congenital NS: rare
* 1st 3monthe of life ,only treatment renal
Drug,Toxic,Allegy : mercury, snake venom, vaccine,
pellicillamine, Heroin, gold, NSAID, captopril, probenecid,
Infection : APSGN, HBV, HIV, shunt nephropathy, reflux
nephropathy, leprosy, syphilis, Schistosomiasis, hydatid
Autoimmune or collagen-vascular diseases : SLE,
Hashimotoᾼs thyroiditis,, HSP, Vasculitis
Metabolic disease : Diabetes mellitus
Neoplasma : Hodgkinᾼs disease, carcinoma ( renal cell, lung,
neuroblastoma, breast, and etc)
Genetic Disease : Alport syn, Sickle cell disease,
Amyloidosis, Congenital nephropathy
Others : Chronic transplant rejection, congenital
Idiopathic NS (INS): Pathology:- Pathology:-
Minimal Change Nephropathy (MCN): < 80%
The glomeruli appear normal basically Under
Light microscopy, and Under
*under Electron microscopy ᾶ fusion of the foot
processes of the podocytes
(2) NonᾷMCN ： ＜20%
*Mesangial proliferative glomerulonephritis
(MsPGN): about 10%
*Focal segmental glomerulosclerosis (FSGS): 5%
*Membranous Nephropathy (MN) : 2%
*Membrane proliferative glomerulonephritis
(MPGN) : 1%
*Others ： rare,Cresent glomerulonephritis
*Nephrotic syndrome is 15 times more common *Nephrotic syndrome is 15 times more common
in children than in adults. in children than in adults.
*Most cases of primary nephrotic syndrome are *Most cases of primary nephrotic syndrome are
in children and are due to minimal-change in children and are due to minimal-change
disease. The age at onset varies with the type disease. The age at onset varies with the type
of nephrotic syndrome. of nephrotic syndrome.
The Main Trigger Of primary Nephrotic
Syndrome and Fundamental and highly
important change of pathophysiology :-
Pathogenesis of Proteinuria:-
Increase glomerular permeability for proteins due to
loss of negative charged glycoprotein
Degree of protineuria:-
Mild less than 0.5g/m2/day
Moderate 0.5 ᾶ 2g/m2/day
Sever more than 2g/m2/day
Type of proteinuria:-
A-Selective proteinuria: where proteins of low
molecular weight .such as albumin, are excreted more
readily than protein of HMW
B-Non selective :
LMW+HMW are lost in urine
pathogenesis of hypoalbuminemia
*Due to hyperproteinuria----- Loss of
plasma protein in urine mainly the
*Increased catabolism of protein during
pathogenesis of hyperlipidemia:-
* Response to Hypoalbuminemia reflex to liver
-- synthesis of generalize protein (
including lipoprotein ) and lipid in the liver ,
the lipoprotein high molecular weight no loss
in urine hyperlipidemia
*Diminished catabolism of lipoprotein
pathogenesis of edema:-
*Reduction plasma colloid osmotic pressure
secondary to hypoalbuminemia Edema and
*Intravascular volume antidiuretic hormone
(ADH ) and aldosterone(ALD) water and
sodium retention Edema
*Intravascular volume glomerular filtration
(GFR) water and sodium retention
How many pathological types
causes nephrotic syndrome?
IN MCNS , The male preponderance of 2:1
: 1.Main manifestations:
Edema (varying degrees) is the common symptom
Local edema : edema in face , around eyes( Periorbital swelling)
, in lower extremities.
Generalized edema (anasarca), edema in penis and scrotum.
Fatigue and lethargy
loss of appetite, nausea and vomiting ,abdominal pain ,
body weight increase, urine output decrease
pleural effusion (respiratory distress)
A-Proteinuria : 3-4 + SELECTIVE.
b-24 urine collection for protein
>40mg/m2/hr for children
c- volume : oliguria (during stage of edema formation)
microscopic hematuria 20%, large number of hyaline
A-serum protein: decrease >5.5gm/dL , Albumin levels
are low ( ＜2.5gm/dL).
B-Serum cholesterol and triglycerides:
Cholesterol ＞5.7mmol/L (220mg/dl).
C-- ESR ＞100mm/hr during activity phase
3.Serum complemen : Vary with clinical type.
2-Frequent relapsing N.S
3-Steroid resistant N.S
6- Low GFR
Differential Diagnosis of NS:
D.D of generalized edema:-
1-Protein ᾶlosing enteropathy
4-Protein energy malnutrition
5-Acute and chronic GN
6-urticaria? Angio edema
Complications of NS:-
1-Infections :Infections is a major complication in children
with NS. It frequently trigger relapses.
Nephrotic pt are liable to infection because :
A-loss of immunoglobins in urine.
B-the edema fluid act as a culture medium.
C-use immunosuppressive agents.
The common infection : URI, peritonitis, cellulitis and
UTI may be seen.
Organisms: encapsulated (Pneumococci, H.
influenzae), Gram negative (e.g E.coli
Vaccines in NS;-
polyvalent pneumococcal vaccine (if not previously
immunized) when the child is in remission and off daily
Children with a negative varicella titer should be given
Hypercoagulability of the blood leading to venous or arterial
Hypercoagulability in Nephrotic syndrome caused by:
1-Higher concentration of I,II, V,VII,VIII,X and fibrinogen
2- Lower level of anticoagulant substance: antithrombin
4-Higher blood viscosity
5- Increased platelet aggregation
6- Overaggressive diuresis
3-ARF : pre-renal and renal
4- cardiovascular disease :-Hyperlipidemia, may be
a risk factor for cardiovascular disease.
6-Others: growth retardation, malnutrition,
adrenal cortical insufficiency
Management of NS:
General (non-specific )
Hospitalization:- for initial work-up and evaluation of
Activity: usually no restriction , except
massive edema,heavy hypertension and
Hypertension and edema: Low salt diet (<2gNa/ day)
only during period of edema or salt-free diet.
Severe edema: Restricting fluid intake
Avoiding infection: very important.
Diuresis : Hydrochlorothiazide (HCT) ：2mg/kg.d
Antisterone ： 2 ～4mg/kg.d
Dextran ： 10 ～15ml/kg , after
followed by Furosemide (Lasix) at
Induction use of albumin:-
Albumin + Lasix (20 % salt poor)
5-Low serum albumin
Prednisone tablets at a dose of 60 mg/m
(maximum daily dose, 80 mg divided into 2-3
doses) for at least 4 consecutive weeks.
After complete absence of proteinuria, prednisone
dose should be tapered to 40 mg/m
every other day as a single morning dose.
The alternate-day dose is then slowly tapered and
discontinued over the next 2-3 mo.
Treatment of relapse in NS:
Many children with nephrotic syndrome will
experience at least 1 relapse (3-4+proteinuria
plus edema ).
daily divided-dose prednisone at the doses noted
earlier ( where he has the relapse ) until the child
enters remission (urine trace or negative for
protein for 3 consecutive days).
The pred-nisone dose is then changed to alternate-
day dosing and tapered over 1-2 mo.
According to response to prednisone
*Remission: no edema, urine is protein free for 5
* Relapse: edema, or first morning urine sample
contains > 2 + protein for 7 consecutive days.
*Frequent relapsing: > 2 relapses within 6 months (>
*Steroid resistant: failure to achieve remission
with prednisolone given daily for 28 days.
Side Effects With Long Term Use of
Steroids ᾿Steroid toxicity
poor healing of wound.
- Pseudotumor cerebri
- Cushingoid features
-Adrenal gland suppression
When can be used:
Steroid-dependent patients, frequent relapsers, and steroid-
Cyclophosphamide Pulse steroids