Dr. Rai Muhammad AsgharAssociate Professor PediatricsHead of Pediatric Department

RMC Rawalpindi

Nephrotic Nephrotic SyndromeSyndrome

DEFINATION DEFINATION

Massive Proteinuria (>40mg/mMassive Proteinuria (>40mg/m22/hr) /hr) Hypoalbuminemia (< 2.5 g/dl)Hypoalbuminemia (< 2.5 g/dl)Edema Edema Hypercholesterolemia (>250mg/dl)Hypercholesterolemia (>250mg/dl)

EpidemiologyEpidemiology

15 times more common in children than adults 15 times more common in children than adults

Incidence is 2-3/ 100,000 children per yearIncidence is 2-3/ 100,000 children per year

EtiologyEtiology

Primary or Idiopathic-Primary or Idiopathic- 90% 90%

1. Minimal change disease 1. Minimal change disease 85% 85% 2. Focal segmental glomerulosclerosis 2. Focal segmental glomerulosclerosis 10% 10% 3. Mesangial proliferative Glomerulonephritis 5% 3. Mesangial proliferative Glomerulonephritis 5%

Secondary- 10%Secondary- 10%

a) Glomerulonephritis a) Glomerulonephritis

Membranous Glomerulonephritis Membranous Glomerulonephritis

Membranoproliferative Glomerulonephritis Membranoproliferative Glomerulonephritis

b) Systemic Diseases b) Systemic Diseases

1. Systemic diseases1. Systemic diseasesHenoch Schonlein Purpura Henoch Schonlein Purpura SLESLEDiabetes mellitusDiabetes mellitus

2. Infections 2. Infections Hepatitis B,& CHepatitis B,& C Infective Endocarditis Infective Endocarditis SyphilisSyphilisMalariaMalariaHIVHIV

3. Drugs- 3. Drugs- Penicillamine Penicillamine Gold salts Gold salts Captopril Captopril NSAID’sNSAID’s

4. Neoplasm's 4. Neoplasm's

Hodgkin’s lymphoma Hodgkin’s lymphoma LeukemiaLeukemiaWilms tumorWilms tumor

PATHOPHYSIOLOGYPATHOPHYSIOLOGY Permeability of glomerular capillary membrane Proteinurea

Hepatic protein synthesis including lipoproteins.

Hyperlipidemia Transudation of fluid from intravascular compartment to interstitial space.

Plasma oncotic pressure.

Intravascular volume

ADH Renal perfusion pressure

Water reabsorption in collecting ducts

Activate renin angiotensin aldosterone system

Tubular reabsorption of sodium & water↑

Edema.

Hypoalbuminimia

PathophysiologyPathophysiology

IDIOPATHIC NEPHROTIC SYNDROMEIDIOPATHIC NEPHROTIC SYNDROME

MINIMAL CHANGE DISEASE FOCAL SEGMENTAL SCLEROSIS

AGE 2-6yrs 2-10yrs SEX 2:1 male 1:3:1 male HEMATURIA 10-20% 60-80% HYPERTENSION 10% 20% RENAL FAILURE No progression 10yrs ASSOCIATIONS None None SERUM CREATININ Inc. in 15-30% Inc. in 20-40%

IIMMUNOGENETICS HLA-B8, B12 None LIGHT MICROSCOPY Normal Focal sclerosis IMMUNOFLUORESCENCE Negative IgM & C3 in lesions ELECTRON MICRO Foot process fusion Foot process fusion STEROID RESPONSE 90% 15-20%

SECONDARY NEPHROTIC SYNDROMESECONDARY NEPHROTIC SYNDROME

Clinical FeaturesClinical Features

Periorbital Puffiness Periorbital Puffiness

More marked is the morning More marked is the morning

Edema later become generalized Edema later become generalized

Scrotal Edema Scrotal Edema

Plural effusion and Ascites is the late featurePlural effusion and Ascites is the late feature

Decrease urine output Decrease urine output

Hypertension and Hematuria are absent Hypertension and Hematuria are absent

Clinical FeaturesClinical Features

InvestigationsInvestigations

1. Urinalysis1. Urinalysis

Proteinuria 3+ or 4+Proteinuria 3+ or 4+Urinary Protein excretion (>40mg/mUrinary Protein excretion (>40mg/m22/hr) /hr)

Urinary Protein & Creatinine ratio > 3 Urinary Protein & Creatinine ratio > 3 Microscopic Hematuria 10% Microscopic Hematuria 10% Pus Cells : Pus Cells : Underlying UTIUnderlying UTI

Cellular Casts:Cellular Casts: not in minimal change disease, common in other not in minimal change disease, common in other formsforms

2.Serum2.Serum

Albumin Albumin < 2.5 g/dl < 2.5 g/dlCholesterolCholesterol >250mg/dl >250mg/dlNormal C3Normal C3Normal renal functionNormal renal function

3.Others3.OthersC.B.C. usually normal, ESR raisedC.B.C. usually normal, ESR raisedMantoux test to rule out TBMantoux test to rule out TBChest X-Ray to rule out Pulmonary pathology or Pleural Chest X-Ray to rule out Pulmonary pathology or Pleural effusion.effusion.

4.Renal Biopsy (Indications)4.Renal Biopsy (Indications)

Steroid Resistant Nephrotic Syndrome Steroid Resistant Nephrotic Syndrome

Frequent RelapsesFrequent Relapses

Steroids Toxicity Steroids Toxicity

Age at onset < 1or >8 yearsAge at onset < 1or >8 years

HypertensionHypertension

Gross HematuriaGross Hematuria

Low plasma C3Low plasma C3

Renal insufficiencyRenal insufficiency

Secondary Nephrotic Syndrome Secondary Nephrotic Syndrome

Important DefinitionsImportant DefinitionsRemission Remission Urine trace or negative for protein for 3 consecutive daysUrine trace or negative for protein for 3 consecutive days

Steroid resistant Steroid resistant If the child continues to have Proteinuria (2 plus or more) on daily If the child continues to have Proteinuria (2 plus or more) on daily steroid therapy after 8 wks. steroid therapy after 8 wks.

Relapse Relapse Proteinuria 3-4 + with Oedema.Proteinuria 3-4 + with Oedema.

Steroid dependent Steroid dependent Relapse while on alternate day therapy or within 28 days of stoppingRelapse while on alternate day therapy or within 28 days of stopping Steroid therapy.Steroid therapy.

Frequent relapser Frequent relapser Four or more relapses in 12 months.Four or more relapses in 12 months.

Management Management SupportiveSupportive

1) Hospitalization (Indications)1) Hospitalization (Indications)

InfectionInfection

Marked EdemaMarked Edema

2) Diet 2) Diet

A balanced diet adequate in proteins and calories A balanced diet adequate in proteins and calories

Salt and fluid restriction when edemaSalt and fluid restriction when edema

3) Infection 3) Infection

Antibiotics Antibiotics

4) Diuretics 4) Diuretics

Indications:Indications:

Pleural Effusion Pleural Effusion

Ascites Ascites

Severe Genital Edema Severe Genital Edema

Treatment (Edema) Treatment (Edema)

Sodium restriction Sodium restriction

Fluid restriction Fluid restriction

Diuretics Diuretics

25 % Salt poor human albumin infusion 25 % Salt poor human albumin infusion

SpecificSpecific 1) 1) Steroids( Oral Prednisolone)Steroids( Oral Prednisolone)

60 mg/60 mg/mm22/day for 4 weeks day for 4 weeks

40 mg/40 mg/mm22/AD for 4 weeks AD for 4 weeks

WithdrawalWithdrawal

Gradual over next 2-3 months Gradual over next 2-3 months

Dose decreased every 2 weeks by 15 mg/mDose decreased every 2 weeks by 15 mg/m22

2) 2) Treatment of steroid dependant and Frequent Treatment of steroid dependant and Frequent relapsersrelapsers

6-12 months AD single dose6-12 months AD single dose

Dose Dose School going 0.5 mg/kg ADSchool going 0.5 mg/kg AD

Preschool Preschool 1 mg/kg/AD 1 mg/kg/AD

3) Alternative Therapy3) Alternative Therapy Indications Indications A) Relapse on Prednisolone dosage > 1 mg/kg AD A) Relapse on Prednisolone dosage > 1 mg/kg AD ORORB) Relapse on Prednisolone dosage > 0.5 mg/kg ADB) Relapse on Prednisolone dosage > 0.5 mg/kg AD PlusPlus

Steroid Toxicity or Severe Relapse Steroid Toxicity or Severe Relapse

DrugsDrugsCyclophosphamideCyclophosphamideLevamisoleLevamisoleCyclosporinCyclosporinChlorambucil Chlorambucil

4) Steroid Resistant Nephrotic Syndrome4) Steroid Resistant Nephrotic Syndrome

Methylprednisolone Methylprednisolone

Cyclophosphamide Cyclophosphamide

ACE inhibitorsACE inhibitors

Angiotensin II Blockers Angiotensin II Blockers

ComplicationsComplications 1)Infections1)Infections

Spontaneous bacterial peritonitisSpontaneous bacterial peritonitis

Pneumonia Pneumonia

UTI UTI

Sepsis Sepsis

Cellulites Cellulites

2)Arterial and Venous Thrombosis2)Arterial and Venous Thrombosis

3) Others3) Others

Steroids and other drugs adverse effects Steroids and other drugs adverse effects

PROGNOSISPROGNOSIS11) ) Responders (78%)Responders (78%)

92 % Minimal Change92 % Minimal Change

8 % Others8 % Others

Non responders (22 %)Non responders (22 %)

25 % Minimal change25 % Minimal change

25%Focal Sclerosis25%Focal Sclerosis

25 % Mesangial Proliferation25 % Mesangial Proliferation

25 % Others25 % Others

22) Response Time ) Response Time

10 % by the end of 110 % by the end of 1stst Week Week

70 %by the end of 270 %by the end of 2ndnd Week Week

85 %by the end of 385 %by the end of 3rdrd Week Week

92 %by the end of 492 %by the end of 4 thth Week Week

33) ) Steroid responsivenessSteroid responsiveness

90 % Minimal change disease 90 % Minimal change disease

50 % Mesangial proliferation 50 % Mesangial proliferation

20 % Focal Sclerosis 20 % Focal Sclerosis

4) Poor prognostic factors are 4) Poor prognostic factors are

HematuriaHematuriaHypertensionHypertension

HypocomplementemiaHypocomplementemia Focal segmental sclerosis Focal segmental sclerosis Steroid resistance Steroid resistance

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