nephrotic syndrome
TRANSCRIPT
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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