Nephrotic Syndrome in Children

1. Nephrotic Syndrome
Child Health II
Speaker : Shriyans jain

2. 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 1801

3. 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 1801

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

5. Etiology
• Genetic
• Secondary
• Idiopathic or Primary

6. 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 521-1

7. 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 521-1

8. Idiopathic
• Minimal Change disease ( >80 % )
• Mesangial proliferation
• Focal segmental Glomerulosclerosis
• Membranous Nephropathy
• Membranoproliferative glomerulonephritis
- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1804

9. Pathophysiology

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

11. 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

12. Clinical Features

13. • 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 1802

14. CLINICAL FEATURES Minimal Change
Nephrotic Syndrome
Focal Segmental
Glomerulosclerosis
Membranous
Nephropathy
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
0 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 521-2

15. 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

16. 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 ???

17. • 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 1804

18. Additional Tests
• C3 and antistreptolysin O
• Chest X ray and tuberculin test
• ANA
• Hepatitis B surface antigen
Ghai Essential Paediatrics,8th edition, page 478
Indications for Biopsy
• Age below 12 months
• Gross or persistent microscopic hematuria
• Low blood C3
• Hypertension
• Impaired renal Function
• Failure of steroid therapy

19. 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 521-2

20. Cause Light
microscopy
Immunoflorescence Electron Microscopy
Minimal Change
Nephrotic
Syndrome
Normal Negative Foot process fusion
Focal Segmental
Glomerulosclerosis
Focal
sclerotic
lesions
IgM, C3 in lesions Foot process fusion
Membranous
Nephropathy
Thickened
GBM
Fine Granular IgG Sub epithelial deposits
Membranoprolifer
ative
Glomerulonephriti
s
Type I Thickened
GBM,
proliferation
Granular IgG, C3 Mesangial and
subendothelial deposits
Type II Lobulation C3 only Dense deposits
- Nelson Textbook of Paediatrics, Vol 2 : page 1803, table 521-2

21. Management

22. 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, 477

23. 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 479

24. 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 479

25. 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 479, 480

26. Complications
• Edema
• Infections
• Thrombotic complications
• Hypovolaemia and Acute renal Failure
• Steroid Toxicity
Ghai Essential Paediatrics,8th edition, page 480, 481

27. 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 481

28. Management of SRNS
• Steroids + calcineurin inhibitors + ACE inhibitors
/ ARBs’ + HMG coenzyme-A + Diuretics
Ghai Essential Paediatrics,8th edition, page 481, 482

29. Prognosis
• Steroid Responsive NS : Good prognosis
( MCNS )
• Steroid Resistant NS : Poor prognosis
( FSGS )
- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1806

30. 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 482