NEPHROTIC SYNDROME

Speaker : Rakesh kumar

DNB PEDIATRICS

Definition

Manifestation of glomerular
disease, characterized by nephrotic
range proteinuria and a triad of
clinical findings associated with large
urinary losses of protein :
hypoalbuminaemia(<2.5gm/dl) ,
edema and hyperlipidemia
(cholestroi>200mg/dl)
- Nelson Textbook of Paediatrics, Vol 3, 20 Edition, page 2
th

Why nephrotic range

Defined as
- Proteinuria >3.5gm/24hrs.
protein excretion of > 40 mg/m2/hr
First morning protein : creatinine ratio of > 2

- Nelson Textbook of Paediatrics, Vol 3, 20th Edition, page 1

Incidence
( paediatric ) ?
1-3 cases per 100,000 children per
year
Higher in underdeveloped countries (
South east Asia )
Occurs at all ages but is most
prevalent in children between the
ages 2-6 years.
It affects more boys than girls, 2:1

Etiology
Genetic
Secondary

Idiopathic or Primary

Genetic causes

Finnish type Congenital Nephrotic Syndrome

Focal Segmental Glomerulosclerosis
Diffuse Mesangial Sclerosis
Denys-Drash Syndrome
Nail Patella Syndrome
Alport Syndrome
Charcot-Marie-tooth disease
Cockayne syndrome
Laurence-Moon-Beidl-Bardet Syndrome
Galloway-Mowat Syndrome
- Nelson Textbook of Paediatrics, Vol 2, 19th edition, page 1802, table

Secondary causes
Infectious:
Hepatitis (B,C) , HIV-1, Malaria, Syphilis,
Toxoplasmosis

Immunological or Allergic:
Castleman Disease, Kimura Disease, Bee
sting, Food allergens,vasculitis
syndrome,serum sickness

Neoplastic
Lymphoma, Leukemia, solid tumor

Drug induced :
Penicillamine, Gold, NSAIDS,, Mercury,
Lithium, Interferon, captopril,
- Nelson Textbook of Paediatrics, Vol3 20th edition, page 2522, table

Idiopathic

Minimal Change disease ( >80 % )

Mesangial proliferation
Focal segmental Glomerulosclerosis
Membranous Nephropathy
Membranoproliferative
glomerulonephritis

- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1

Pathophysiology

70-100nm

In idiopathic, heredietary and

secondary forms of nephrotic
syndrome, immune and nonimmune insult to the podocyte
leading to foot process effacement of
the podocyte, thus decreasing number
of functional podocyte and altered silt
diaphragm Integrity, result is increase
in protein loss across the glomerular
capillary wall into the urinary sapce.

- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1

Clinical Features

 Edema: most common symptom

starts with mild edema peri orbital puffiness,
lower extremities
Progression to generalized edema, ascites,
pleural effusion, genital edema

Decreased urine output

Anorexia, Irritability, Abdominal pain and
diarrhoea

- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1

CLINICAL
FEATURES

Minimal Change
Nephrotic
Syndrome

Focal
Segmental
Glomeruloscle
rosis

Membrano
us
Nephropat
hy

Age ( yr )

2- 6

2 - 10

40 - 50

Sex ( M : F )

2:1

1.3 : 1

2:1

Nephrotic
Syndrome

100 %

90 %

80 %

Asymptomatic
proteinuria

10 %

20 %

Hematuria

10 20 %

60 80 %

60 %

Hypertension

10 %

20 % early

infrequent

Rate of
progression to
renal failure

Non progressive

10 yrs

50 % in 10
20 yrs

Associated
Conditions

Usually none

None

Renal vein
thrombosis,
SLE,
Hepatitis B

- Nelson Textbook of Paediatrics, Vol 3 : page 2527, table 5

DIFFERENTIALS

Protein losing enteropathy

Hepatic failure
Heart failure
Acute/Chronic Glomerulonephritis
Protein Malnutrition

A diagnosis other than MCD should be

considered
< 1 year old
Family history of nephrotic Syndrome
Hypertension
Pulmonary edema
Gross hematuria

EVALUATION
Proper History and Examination
Features of systemic disorder must be
looked for
fever
Rash
Joint pain
HSM
LAP

Lab Investigations
Urine Examination
Complete Blood Count & Blood picture
Renal parameters :
Spot Urine Protein : Creatinine ratio
Urinary protein excretion
protein selectivity ratio

Liver Function Test

Renal Biopsy ???

 Urinalysis - 3+ to 4+ proteinuria
Renal Function
Spot UPC ratio > 2.0
- 24 hr urinary protein is not
essential
Repeated microscopy examination of
urine sediment should be looked
for Red cells.
If, persistentely present it indicates
significant Renal histological lesion.
Pediatrics Nephrology 6th edition R N
srivastava.Arvind Bagga page 199
Nelson Textbook of Paediatrics, Vol 3, 20th

BLOOD EXAMINATION:
Serum Creatinine normal or elevated,
Persistentely elevated serum creatinine
level suggests significant renal
histological lesion.
Serum albumin - < 2.5 gm/dl
Serum Cholesterol >250mg/dl
Serum Complement levels Normal or
low, usually Low levels seen in MPGN.
Hyponatremia if present is dilutional
needs no correction
Pediatrics Nephrology 6th edition R N srivastava.Arvind Bagga
page 199

Additional Tests

C3.
Chest X ray and tuberculin test
ANA,dsDNA,
Hepatitis B surface antigen,Anti HCV
and HIV in High risk population
Indications for Biopsy
Age below 12 months and > 12 years
Gross or persistent microscopic
hematuria
Low blood C3
Hypertension
Impaired renal Function

Ghai Essential Paediatrics,8th edition, page 4

Idiopathic

Lab Findings

Minimal Change Nephrotic

Syndrome

Raised BUN in 15 30 %
Highly Selective
proteinuria

Focal Segmental
Glomerulosclerosis

Raised BUN in 20 40 %

Membranous Nephropathy

Membranoproliferative
Glomerulonephritis

Type I

Low C1, C4 , C3 C9

Type II

Normal C1, C4 , Low C3

C9

- Nelson Textbook of Paediatrics, Vol 3 : page 2527, table

Cause

Light

Immunofloresc
ence

Electron
Microscopy

Negative

Foot process fusion

microsc
opy
Minimal Change
Nephrotic
Syndrome

Normal

Focal
Segmental
Glomerulosclero
sis

Focal
sclerotic
lesions

IgM, C3 in lesions Foot process fusion

Membranous
Nephropathy

Thickene
d GBM

Fine Granular IgG Sub epithelial

deposits

Membranoprolif Type
erative
I
Glomerulonephr
itis

Thickene Granular IgG, C3

d GBM,
proliferati
on

Mesangial and
subendothelial
deposits

- Nelson Textbook of Paediatrics, Vol 3 : page 2527, table 5

Management

Initial Episode
Corticosteroid therapy with
Prednisolone or prednisone
( 2mg/kg per day for 6 weeks followed
by
1.5 mg/kg single morning dose on
alternate days for
6 weeks )

Pediatrics Nephrology 6th edition R N srivastava.Arvind Bagg

Ghai Essential Paediatrics,8th edition, page 476, 477

Management of clinical sequalae

of Nephrotic syndrome
Dietary Management
- Sodium restriction < 1.5gm/day
- Water/ Fluid restiction if child is
hyponatremic.
- Scrotum should be elevated with pillow.
-Adequate protein intake up to 2-3 gm /kg/day is
recommended ,however in non-minimal lesions and
steroid resistance nephrotic syndrome with heavy
proteinuria the dietary protein shold be restricted to
1.5 gm/kg/day.
- Calcium and vit. D supplements are required in
persistent heavy proteinuria.

Edema
- Sodium restriction < 1.5gm/day
- Water/ Fluid restiction if child is
hyponatremic.
- Scrotum should be elevated with
pillow.
- Furosemide , Bumetanide, Toresemide,
Thiazide,Spironolactone, Trimetrine can be
given if there significant edema.
- Furosemide 1-3 mg/kg in 1-2 divided
doses, dose can be increased up to 46mg/kg.

In very edematous pt. with low urinary

excretion of sodium add another diuretic
with different site of action like
Hydrochlorothiazide(1-3 mg/kg /day) or
Metazolone(0.5-1 mg/kg/day)
They must be given one hr.before
furosemide. So, that distal sod. Absobing
site are blocked.
Occasionally pt. have massive anasarca
with hypoalbuminemia<1.5g/dl with
features oh hypovolemia.such pts benefit
from 20% albumin infusion @0.5g/kg BW.

- Head out Water immersion:

-Ultrafiltration

COMPLICATIONS:
Infection: commonest causes streptococcal pneumoniae.
Peritonitis: diag. by examonation of ascitic fluid which may
be hazy or frankly turbid presence of neutrophils.75100/mm3 is confirmatory. Culture usually shows
s.pneumoniae and occasionally E.Coli
T/t is monotherapy with Ceftriaxone or Cefotaxime for 710 days in septemic dose.
Cellulitis: is also common, initiating factors are vene
puncture , milder trauma ,skin breaks
Organisms are b-Hemolytic streptococci, Staph..
H.influenza .
T/t prefered I.V. CEFTRIAXONE AND cloxacillind
Varicella and Measles usually flare up while pt. on steroid
therapy. They must be treated with Ig and I.V. Acyclovir.

Dyslipidemia: Manage with

Low fat diet iess than 30% of total calorie
ana saturated fats <10% of total calories.
cholesterol intake should be < 300mg/day.
There is less evidence of HMG CO-A
REDUCTASE INHIBITORS.
Thromboembolism: confirmed by appropriate
imaging study.
Anticoagulation with Heparin , Low molecular
wt.,Warferin can be uased .
Immunization: IAP recommends 2-4 dose of
pneumoccal conjugate vaccine for child < 2 years.
from 2-5 years 2 doses f/b 8wks laters by 1 dose
of 23 valent pcv.

Subsequent course
Relapse
Infrequent Relapsers : one relapses in 6
months.
Frequent Relapsers : >2 relapses within 6
months or 4 or more relapses per year

Steroid therapy
Steroid dependant :2 consecutive relapses
following dose reduction or 2 wks its
discontinuation
Steroid resistant : Partial or no response
despites 4 wks of treatment.

Management of Relapse
Parent Education
Symptomatic therapy for infections
in case of low grade proteinuria
Persistent proteinuria ( 3 - 4+ )
Prednisolone
( 2mg/kg/day until protein is negative
for 3 days )
1.5 mg/kg on alternate days for 4
weeks )

Frequent Relapses
Alternate Day prednisolone
Steroid sparing agents
Levamisole ( 2 2.5 mg/kg )
Cyclophosphamide ( 2 2.5 mg/kg/day)
Mycophenolate Mofetil ( 20 25
mg/kg/day )
Cyclosporin ( 4 5 mg/kg/day )
Tacrolimus (0.1 0.2 mg/kg/day )
Rituximab ( 375mg/m2 IV once a week )

Steroid Resistant Nephrotic

Syndrome
Diagnosis Lack of response to
prednisolone therapy for 4 weeks
Indication for renal biopsy ,
Etiology
10 20 % - Genetic ( Mutations in genes
encoding podocyte proteins )

Indications for mutational analysis :

Congenital Nephrotic Syndrome
Family History of SRNS
Sporadic resistance to steroids
Girls with steroid resistant FSGS

Management of SRNS
Steroids + calcineurin inhibitors + ACE
inhibitors / ARBs + HMG coenzyme-A
+ Diuretics

Prognosis
Steroid Responsive NS : Good
prognosis
( MCNS )
Steroid Resistant NS : Poor prognosis
( FSGS )

Congenital Nephrotic
Syndrome
Presents in first 3 months of life
Anasarca, hypoalbuminaemia, oliguria
Finnish Type Nephrotic Syndrome
Antenatally detectable :
Raised AFP in maternal serum and amniotic fluid

Complications
Failure o thrive
Infections
Hypothyroidism
Renal Failure ( 2 3 yrs )

THANK YOU

Ghai Essential Paediatrics,8th edition, page 4