Child Health II

Nephrotic
Syndrome
Speaker : Shriyans

Definition

Manifestation of glomerular
disease, characterized by nephrotic
range proteinuria and a triad of
clinical findings associated with large
urinary losses of protein :
hypoalbuminaemia , edema and
hyperlipidemia

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

Why nephrotic range

Defined as
protein excretion of > 40 mg/m2/hr
First morning protein : creatinine ratio of
> 2-3 : 1
Other causes of proteinuria

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

Incidence
( paediatric ) ?
2 7 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 1.5-6 years.
It affects more boys than girls, 2:1

http://www.kidney.org/site/107/pdf/NephroticSyndrome.pdf

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
Congenital
Oligomeganephronia

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

Inflammatory
Glomerulonephritis

Immunological
Castleman Disease, Kimura Disease, Bee sting, Food allergens

Neoplastic
Lymphoma, Leukemia

Traumatic ( Drug induced )

Penicillamine, Gold, NSAIDS, Pamidronate, Mercury, Lithium

- Nelson Textbook of Paediatrics, Vol 2,19th edition, page 1802, 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

http://www.highlands.edu/academics/divisions/scipe/biology/faculty/harnden/2122/images/renalcorpuscle.jpg

Complex disturbances in
immune system

Genetic Mutations /
Mutations in proteins

Extensive effacement of podocyte foot processes

Increased permeability of the glomerular capillary wall
Massive proteinuria
Hypoalbuminaemia
Edema

Clinical Features

 Edema
Mild to start with peri orbital puffiness, lower
extremities
Progression to generalized edema, ascites,
pleural effusion, genital edema

Decreased urine output

Anorexia, Irritability, Abdominal pain and
diarrhoea
Absence of
Hypertension
Gross hematuria

- 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 2 : page 1803, table 5

DIFFERENTIALS

Protein losing enteropathy

Hepatic failure
Heart failure
Acute/Chronic Glomerulonephritis
Protein Malnutrition
< 1 year old
Family history of nephrotic Syndrome
Hypertension
Pulmonary edema
Gross hematuria
Extrarenal findings

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
UPE > 40 mg/m2/hr
Serum Creatinine normal or elevated
Serum albumin - < 2.5 gm/dl
Serum Cholesterol/ TGA levels
elevated
Serum Complement levels Normal or
low

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

Additional Tests

C3 and antistreptolysin O
Chest X ray and tuberculin test
ANA
Hepatitis B surface antigen

Indications for Biopsy

Age below 12 months
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 2 : page 1803, table 5

Cause

Light
microsco
py

Immunofloresc
ence

Electron
Microscopy

Minimal
Change
Nephrotic
Syndrome

Normal

Negative

Foot process fusion

Focal
Segmental
Glomeruloscler
osis

Focal
sclerotic
lesions

IgM, C3 in lesions Foot process fusion

Membranous
Nephropathy

Thickened
GBM

Fine Granular IgG Sub epithelial

deposits

Thickened
GBM,
proliferati
on

Granular IgG, C3

Membranoproli
ferative
Glomeruloneph
ritis

Type
I

Mesangial and
subendothelial
deposits

- Nelson Textbook of Paediatrics, Vol 2 : page 1803, table 5

Management

Initial Episode

High protein diet

Salt moderation
Treatment of infections
If significant edema diuretics
Aldosterone
antagonist ( Fursemide, spironolactone )
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 )

Ghai Essential Paediatrics,8th edition, page 476, 4

Subsequent course
Relapse
Infrequent Relapsers : 3 or less
relapses per year
Frequent Relapsers : 4 or more
relapses per year

Steroid therapy
Steroid dependant : relapse following
dose reduction or discontinuation
Steroid resistant : Partial or no
response to initial treatment

Ghai Essential Paediatrics,8th edition, page 4

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 )

Ghai Essential Paediatrics,8th edition, page 4

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 )
Ghai Essential Paediatrics,8th edition, page

Complications

Edema
Infections
Thrombotic complications
Hypovolaemia and Acute renal
Failure
Steroid Toxicity

Ghai Essential Paediatrics,8th edition, page 480, 4

Steroid Resistant Nephrotic

Syndrome
Diagnosis Lack of response to
prednisolone therapy for 4 weeks
Indication for renal biopsy , BBVS
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

Ghai Essential Paediatrics,8th edition, page 4

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

Ghai Essential Paediatrics,8th edition, page 481, 4

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

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

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 )

Ghai Essential Paediatrics,8th edition, page 4