Nephrotic syndrome

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Text of Nephrotic syndrome

  • Dr. Rai Muhammad Asghar Associate Professor Pediatrics Head of Pediatric DepartmentRMC Rawalpindi

  • Nephrotic Syndrome

  • DEFINATION

    Massive Proteinuria (>40mg/m2/hr) Hypoalbuminemia (< 2.5 g/dl)Edema Hypercholesterolemia (>250mg/dl)

  • Epidemiology

    15 times more common in children than adults

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

  • Etiology

    Primary or Idiopathic- 90% 1. Minimal change disease 85% 2. Focal segmental glomerulosclerosis 10% 3. Mesangial proliferative Glomerulonephritis 5%

  • Secondary- 10% a) Glomerulonephritis Membranous Glomerulonephritis Membranoproliferative Glomerulonephritis

    b) Systemic Diseases 1. Systemic diseases Henoch Schonlein Purpura SLE Diabetes mellitus

  • 2. Infections Hepatitis B,& C Infective Endocarditis SyphilisMalariaHIV 3. Drugs- Penicillamine Gold salts Captopril NSAIDs

    4. Neoplasm's Hodgkins lymphoma LeukemiaWilms tumor

  • PATHOPHYSIOLOGY Permeability of glomerular capillary membraneProteinurea Hepatic protein synthesis including lipoproteins.HyperlipidemiaTransudation of fluid from intravascular compartment to interstitial space.Plasma oncotic pressure.Intravascular volumeADHRenal perfusion pressureWater reabsorption in collecting ductsActivate renin angiotensin aldosterone systemTubular reabsorption of sodium & waterEdema.Hypoalbuminimia

  • Pathophysiology

  • IDIOPATHIC 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 SYNDROME

    MEMBRANOUS NEPHROPATY

    MEMBRANOPROLIFERATIVE

    TYPE 1

    TYPE 2

    AGE

    10-20yrs

    5-15yrs

    5-15yrs

    SEX

    2:1 male

    Male: female

    Male: female

    HEMATURIA

    60%

    80%

    80%

    HYPERTENSION

    Infrequent

    35%

    35%

    RENAL FAILURE

    10-20 yrs

    10-20yrs

    5-15yrs

    ASSOCIATIONS

    CA,SLE,HBV

    None

    Lipodystrophy

    LAB FINDING

    LCI, C4, C3-9

    C1,C4,N/ C3, C9L

    LIGHT MICROSCOPE

    Thick GBM, Spikes

    Thick GBM

    Lobulation

    IMMUNOFLOUR

    Fine IgG, C3

    Granular IgG, C3

    C3 ONLY

    ELECTRON MICRO

    SE deposits

    Mesangial & SE

    Dense deposits

    STEROID RESPONSE

    Slow progression

    Not Established

    Not Established

  • Clinical FeaturesPeriorbital Puffiness More marked is the morning Edema later become generalized Scrotal Edema Plural effusion and Ascites is the late feature Decrease urine output Hypertension and Hematuria are absent

  • Clinical Features

  • Investigations

    1. Urinalysis

    Proteinuria 3+ or 4+Urinary Protein excretion (>40mg/m2/hr) Urinary Protein & Creatinine ratio > 3 Microscopic Hematuria 10% Pus Cells :Underlying UTICellular Casts:not in minimal change disease, common in other forms

  • 2.Serum Albumin < 2.5 g/dl Cholesterol >250mg/dl Normal C3 Normal renal function 3.Others C.B.C. usually normal, ESR raised Mantoux test to rule out TB Chest X-Ray to rule out Pulmonary pathology or Pleural effusion.

  • 4.Renal Biopsy (Indications)

    Steroid Resistant Nephrotic Syndrome Frequent RelapsesSteroids Toxicity Age at onset < 1or >8 yearsHypertensionGross HematuriaLow plasma C3Renal insufficiencySecondary Nephrotic Syndrome

  • Important DefinitionsRemission Urine trace or negative for protein for 3 consecutive days

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

    Relapse Proteinuria 3-4 + with Oedema.

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

    Frequent relapser Four or more relapses in 12 months.

  • Management Supportive

    1) Hospitalization (Indications) Infection Marked Edema2) Diet A balanced diet adequate in proteins and calories Salt and fluid restriction when edema3) Infection Antibiotics

  • 4) Diuretics Indications: Pleural Effusion Ascites Severe Genital Edema Treatment (Edema) Sodium restriction Fluid restriction Diuretics 25 % Salt poor human albumin infusion

  • Specific 1) Steroids( Oral Prednisolone) 60 mg/m2/day for 4 weeks 40 mg/m2/AD for 4 weeks Withdrawal Gradual over next 2-3 months Dose decreased every 2 weeks by 15 mg/m2

  • 2) Treatment of steroid dependant and Frequent relapsers

    6-12 months AD single doseDose School going 0.5 mg/kg ADPreschool 1 mg/kg/AD

  • 3) Alternative Therapy Indications A) Relapse on Prednisolone dosage > 1 mg/kg AD ORB) Relapse on Prednisolone dosage > 0.5 mg/kg AD Plus Steroid Toxicity or Severe Relapse DrugsCyclophosphamideLevamisoleCyclosporinChlorambucil

  • 4) Steroid Resistant Nephrotic Syndrome

    Methylprednisolone Cyclophosphamide ACE inhibitorsAngiotensin II Blockers

  • Complications 1)Infections Spontaneous bacterial peritonitisPneumonia UTI Sepsis Cellulites 2)Arterial and Venous Thrombosis 3) Others Steroids and other drugs adverse effects

  • PROGNOSIS1) Responders (78%) 92 % Minimal Change8 % Others Non responders (22 %) 25 % Minimal change25%Focal Sclerosis25 % Mesangial Proliferation25 % Others

    2) Response Time 10 % by the end of 1st Week70 %by the end of 2nd Week85 %by the end of 3rd Week92 %by the end of 4th Week

  • 3) Steroid responsiveness90 % Minimal change disease 50 % Mesangial proliferation 20 % Focal Sclerosis

    4) Poor prognostic factors are Hematuria Hypertension Hypocomplementemia Focal segmental sclerosis Steroid resistance

  • Thank You