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Prepared by Dr Rajesh T Eapen ATLAS HOSPITAL RUWI

Nephrotic Syndrome

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Page 1: Nephrotic Syndrome

Prepared by

Dr Rajesh T Eapen

ATLAS HOSPITAL

RUWI

Page 2: Nephrotic Syndrome

Introduction

• Nephrotic syndrome (NS)

– Commonest glomerular disease

affecting children

– Frequently encountered in general

paediatrics

– Characterised by

• Significant proteinuria (early morning urine

protein to creatinine ratio > 200mg/mmol)

leading to

– Hypoalbuminaemia (plasma albumin of < 25g/l)

Paediatrics and child health 2010;20(1):36-42

Page 3: Nephrotic Syndrome

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

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Why ‘nephrotic range’

• Defined as

– protein excretion of > 40 mg/m2/hr

– First morning protein : creatinine ratio of > 2-3 : 1

- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1801

Page 6: Nephrotic Syndrome

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

Page 7: Nephrotic Syndrome

Etiology

• Genetic

• Secondary

• Idiopathic or Primary

Page 8: Nephrotic Syndrome

Genetic causes

• Finnish type Congenital NephroticSyndrome

• 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

Page 9: Nephrotic Syndrome

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

Page 10: Nephrotic Syndrome

Idiopathic

• Minimal Change disease ( >80 % )

• Mesangial proliferation

• Focal segmental Glomerulosclerosis

• Membranous Nephropathy

• Membranoproliferative

glomerulonephritis

- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1804

Page 11: Nephrotic Syndrome

Pathophysiology

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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

Page 14: Nephrotic Syndrome
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PATHOPHYSIOLOGY

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Clinical Features

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alterations

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CLINICAL

FEATURES

Minimal Change

Nephrotic

Syndrome

Focal

Segmental

Glomeruloscler

osis

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

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DIFFERENTIAL

DIAGNOSIS

• 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

Page 24: Nephrotic Syndrome

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 ???

Page 25: Nephrotic Syndrome

• 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

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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

Page 27: Nephrotic Syndrome

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

Page 28: Nephrotic Syndrome

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

Membranoproliferative

GlomerulonephritisType 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

Page 29: Nephrotic Syndrome

Management

Page 30: Nephrotic Syndrome

Initial Episode

• High protein diet

• Salt moderation

• Treatment of infections

• If significant edema – diuretics Aldosterone antagonist ( Furosemide, spironolactone )

• Corticosteroid therapy with Prednisoloneor 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

Page 31: Nephrotic Syndrome

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

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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

Page 33: Nephrotic Syndrome

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

Page 34: Nephrotic Syndrome

Complications

• Edema

• Infections

• Thrombotic complications

• Hypovolaemia and Acute renal

Failure

• Steroid Toxicity

Ghai Essential Paediatrics,8th edition, page 480, 481

Page 35: Nephrotic Syndrome

Steroid Resistant Nephrotic

Syndrome

• Diagnosis – Lack of response to prednisolonetherapy 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 FSGSGhai Essential Paediatrics,8th edition, page 481

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Management of SRNS

• Steroids + calcineurin inhibitors + ACE

inhibitors / ARBs’ + HMG coenzyme-A +

Diuretics

Ghai Essential Paediatrics,8th edition, page 481, 482

Page 37: Nephrotic Syndrome

Prognosis

• Steroid Responsive NS : Good

prognosis ( MCNS )

• Steroid Resistant NS : Poor prognosis

( FSGS )

- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1806

Page 38: Nephrotic Syndrome

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

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Dietary management of ns

A balanced diet, adequate in

protein (1.5-2 g/kg) and calories

is recommended

Patients with persistent

proteinuria should receive 2-2.5

g/kg of protein daily

< 30% calories should be

derived from fat and saturated

fats avoided

Page 46: Nephrotic Syndrome

• A ‘no added salt’ diet is advisable

in view of the salt and water

overload

• There is no evidence for use of a

high protein diet

• Children should be encouraged to

have a normal healthy diet

Page 47: Nephrotic Syndrome

• Weight control

–In between meal snacks such as biscuits, crisps, and fizzy (high sugar) drinks should be avoided with low energy alternatives promoted

–Healthy eating advice should again be reinforced

Page 48: Nephrotic Syndrome

• Steroid resistant nephroticsyndrome

–Vitamin supplementation and iron treatment may also be indicated

–Such children are often hospitalised for long periods and the clinical course may be complicated by diarrhoea and other nosocomial infections from the ward

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prognosis

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Due to loss of

proteins in the urineDue to ↓ oncotic

pressure

•Immunoglobulin

↑susceptibility to infection

•antithrombin III and proteins

C and S

Thromboembolism

•vit D–binding protein

vit D deficiency

•Transferrin

Iron deficiency anemia

•Hyperlipidaemia

•Hypovolemia

Acute renal failure

•Anasarca

risk of cellulitis, bacterial

peritonitis with ascites

,large pleural effusions

or pulmonary edema

Page 52: Nephrotic Syndrome