Prepared by:-

Mohammad Ali Al-shehri

..
Supervised by :
Dr.
Nephrotic Syndrome..(NS) Nephrotic Syndrome..(NS)
Introduction
Definition of NS
Etiology of NS
Pathology of NS
Pathophysiology of NS
Clinical Manifestation of NS
Complication NS
Laboratory Data
Diagnosis
Treatment
Nephrotic syndrome Nephrotic syndrome
Nephrotic syndrome (NS) results from
increased permeability of Glomeulrar
basement membrane ( GBM ) to plasma
protein.

It is clinical and laboratory syndrome
characterized by massive proteinuria, which
lead to hypoproteinemia ( hypo-
albuminemia), hyperlipidemia and pitting
edema.

(4-increase, 1-decrease).
Nephrotic Criteria:-
*Massive proteinuria:
qualitative proteinuria: 3+ or 4+,
quantitative proteinuria : more than 40
mg/m2/hr in children (selective).
*Hypo-proteinemia :
total plasma proteins < 5.5g/dl and serum
albumin : < 2.5g/dl.
*Hyperlipidemia :
serum cholesterol : > 5.7mmol/L

*Edema : pitting edema in different degree
Nephr i tic Criteria
-Hematuria: RBC in urine (gross hematuria)
-Hypertension:
130/90 mmHg in school-age children
120/80 mmHg in preschool-age children
110/70 mmHg in infant and toddlers children
-Azotemia renal insufficiency :
Increased level of serum BUN Cr
-Hypo-complementemia:
Decreased level of serum c3
Classification:
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 T cell function.
Accounting for 90% of NS in child. mainly discussed .
B-Secondary NS:
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
transplantation
Secondary NS

Drug,Toxic,Allegy : mercury, snake venom, vaccine,
pellicillamine, Heroin, gold, NSAID, captopril, probenecid,
volatile hydrocarbons
Infection : APSGN, HBV, HIV, shunt nephropathy, reflux
nephropathy, leprosy, syphilis, Schistosomiasis, hydatid
disease
Autoimmune or collagen-vascular diseases : SLE,
Hashimotos thyroiditis,, HSP, Vasculitis
Metabolic disease : Diabetes mellitus
Neoplasma : Hodgkins disease, carcinoma ( renal cell, lung,
neuroblastoma, breast, and etc)
Genetic Disease : Alport syn, Sickle cell disease,
Amyloidosis, Congenital nephropathy
Others : Chronic transplant rejection, congenital
nephrosclerosis
Idiopathic NS (INS): Pathology:- Pathology:-
Minimal Change Nephropathy (MCN): < 80%
The glomeruli appear normal basically Under
Light microscopy, and Under
Immunofluorescence
*under Electron microscopy fusion of the foot
processes of the podocytes
(2) NonMCN 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
NB:-
*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.
Pathophysiology:
The Main Trigger Of primary Nephrotic
Syndrome and Fundamental and highly
important change of pathophysiology :-
Proteinuria
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 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
albumin.

*Increased catabolism of protein during
acute phase.
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
hypovolemia
*Intravascular volume antidiuretic hormone
(ADH ) and aldosterone(ALD) water and
sodium retention Edema
*Intravascular volume glomerular filtration
rate
(GFR) water and sodium retention
Edema
How many pathological types
causes nephrotic syndrome?
Clinical Manifestation:-
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.
2-Non-specific symptoms:
Fatigue and lethargy
loss of appetite, nausea and vomiting ,abdominal pain ,
diarrhea
body weight increase, urine output decrease
pleural effusion (respiratory distress)
Investigations:-
1-Urine analysis:-
A-Proteinuria : 3-4 + SELECTIVE.
b-24 urine collection for protein
>40mg/m2/hr for children
c- volume : oliguria (during stage of edema formation)
d-Microscopically:-
microscopic hematuria 20%, large number of hyaline
cast
Investigations:-
2-Blood:
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-- ESR100mm/hr during activity phase
.
3.Serum complemen : Vary with clinical type.

4.Renal function
.

Kidney Biopsy:-
Considered in:
1-Secondary N.S
2-Frequent relapsing N.S
3-Steroid resistant N.S
4- Hematuria
5-Hypertension
6- Low GFR
Differential Diagnosis of NS:
D.D of generalized edema:-
1-Protein losing enteropathy
2-Hepatic Failure.
3-HF
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.
D- malnutrition
The common infection : URI, peritonitis, cellulitis and
UTI may be seen.
Organisms: encapsulated (Pneumococci, H.
influenzae), Gram negative (e.g E.coli
Complication
Vaccines in NS;-
polyvalent pneumococcal vaccine (if not previously
immunized) when the child is in remission and off daily
prednisone therapy.
Children with a negative varicella titer should be given
varicella vaccine.
Complication..
2-Hypercoagulability (Thrombosis).
Hypercoagulability of the blood leading to venous or arterial
thrombosis:
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
III
3-decrease fibrinolysis.
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.
5-Hypovolemic shock
6-Others: growth retardation, malnutrition,
adrenal cortical insufficiency
Management of NS:
General (non-specific )
*Corticosteroid therapy
General therapy:-
Hospitalization:- for initial work-up and evaluation of
treatment.
Activity: usually no restriction , except
massive edema,heavy hypertension and
infection.
Diet
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
30 60m,
followed by Furosemide (Lasix) at
2mg/kg .
Induction use of albumin:-
Albumin + Lasix (20 % salt poor)
1-Severe edema
2-Ascites
3-Pleural effusion
4-Genital edema
5-Low serum albumin
Corticosteroidprednisone therapy:-
Prednisone tablets at a dose of 60 mg/m
2
/day
(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
2
/day given
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
therapy:
*Remission: no edema, urine is protein free for 5
consecutive days.

* Relapse: edema, or first morning urine sample
contains > 2 + protein for 7 consecutive days.
*Frequent relapsing: > 2 relapses within 6 months (>
4/year).
*Steroid resistant: failure to achieve remission
with prednisolone given daily for 28 days.
Side Effects With Long Term Use of
Steroids Steroid toxicity
hyperglycemia
myopathy
peptic ulcer
poor healing of wound.
Hirsutism
Thromboembolism
-Stunted growth
Cataracts
- Pseudotumor cerebri
-Psycosis
-Osteoporosis
- Cushingoid features
-Adrenal gland suppression
Alternative agent:-
When can be used:
Steroid-dependent patients, frequent relapsers, and steroid-
resistant patients.
Cyclophosphamide Pulse steroids
Cyclosporin A
Tacrolimus
Microphenolate
THE END.
THANK YOU.
THANK YOU.