Nephrotic Syndrome Presented by Dr. Huma Daniel

Characteristic Features Heavy proteinuria > 40mg/m2/hr Hypoalbuminemia <2.5g/dl Edema Hyperlipidema >250mg/dl

Epidemiology 15 times more common in children than adults incidence is 2-3/ 100,000 children per year incidence higher is Asian population 16/100,000 children

Etiology IDIOPATHIC NEPHROTIC SYNDROME (90%) Minimal change disease 85% Mesengial proliferation 5% Focal segmental glomerulosclerosis 10%

Etiology SECONDARY NEPHROTIC SYNDROME (10%): 1. Renal Causes: Membranous nephropathy Membranoproliferative glomerulonephtritis 2. Extra Renal Causes: Infection Drugs Neoplasia Systemic diseases Allergic reactions Familial disorders Circulatory disorders

Pathophysiology

Pathophysiology

IDIOPATHIC NEPHROTIC SYNDROME

SECONDARY NEPHROTIC SYNDROME

Clinical Features HISTORY Preceding flu-like illness General health (anorexia, wt. gain ,lethargy) Edema Urinary symptoms (hematuria, oliguria) Infection, diarrhea, abd. pain Drug intake Past history

Clinical Features EXAMINAITON Vital & bp Height & weight for age Anemia Periorbital puffiness Lymphadenopathy Pleural effusion, ascites Ankle, sacral, genital edema

Clinical Features

Diagnosis URINE ANALYSIS: PROTEINURIA: 3+ Or 4+ 24HRS URINARY PROTEIN EXCRETION: Children : >40mg/m2/hr URINARY PROTEIN TO CREATININE RATIO: >2.0 MICROSCOPIC HEMATURIA: 20% PUS CELLS: underlying UTI CELLULAR CASTS: not in minimal change disease, common in other forms

Diagnosis SERUM: S. CREATININE: Normal S. CHOLESTROL: Elevated S. ALBUMIN: <2.5g/dl C3 & C4: TOTAL CALCIUM: Decreased

Diagnosis OTHERS: X-RAY CHEST: VITRAL SEROLOGY: BLOOD COUNTS: HBV associated with membranous nephritis & HCV with mesengial proliferation BLOOD COUNTS: TLC & DLC Normal ESR raised X-RAY CHEST: R/O pulmonary pathology or pleural effusion

Diagnosis MANTOUX TEST: RENAL BIOPSY R/O Tb before starting steroids ANA: R/O SLE

SCHEME FOR MANAGEMENT OF CHILDREN WITH NEPHROTIC SYNDROME

SCHEME FOR MANAGEMENT OF CHILDREN WITH NEPHROTIC SYNDROME

SCHEME FOR MANAGEMENT OF CHILDREN WITH NEPHROTIC SYNDROME

Management of Nephrotic Syndrome DIETARY ADVICE: A balanced diet adequate in proteins and calories is recommended Edema no added salt foods high in sodium avoided

Management of Nephrotic Syndrome DIURETICS: INDICATIONS: Severe symptomatic edema Steroid toxicity or steroid contraindicated DOSAGE & ADMINISTRATION: Chlorothiazide 10mg/kg/doze I/V 12hrly or Metolazome 0.1mg/kg/doze PO bid followed by Furosemide 30mins later 1-2mg/kg/doze I/V 12 hrly

Management of Nephrotic Syndrome ROLE OF INTRAVENOUS ALBUMIN INDICATIONS: Signs of hypovolemia DOSAGE & ADMINISTRATION: I/V salt poor 25% albumin infusion 0.5-1 gm/kg/doze over 6-12 hrs followed by Frusemide 1-2 mg/kg/doze I/V

Management of Nephrotic Syndrome CORTICOSTEROID THERAPY: DOSAGE & ADMINISTRATION: Prednisolone 60mg/m2/day (max 80mg) divided into 2-3 doses for 4 consecutive wks 80-90% ------- remission in 10days after 4wks course, prednisolone tapered to 40mg/m2/day on alternate days as single morning dose Alternate day dose tapered slowly & discontinued over 2-3 months

Management of Nephrotic Syndrome REPONSE TO STEROID: 10% respond by first week 70% by second week 85% by third week 92% by forth week

Management of Nephrotic Syndrome CORTICOSTEROID THERAPY RESPONSE TO STEROIDS: STEROID RESPONSIVE PATIENTS: 70-90% pts . Responsive >75% at least 1 relapse Treated using protocol already described FREQUENT RELAPSER: 4 or more relapses in 12 months Alternate day prednisolone tapered over 6 months Alternative therapy

Management of Nephrotic Syndrome CORTICOSTEROID THERAPY RESPONSE TO STEROIDS: STEROID DEPENDENT: Relapses on 2 consective occasion as prenisolone is being decreased or within 28daysof stopping prednisolone Alternative therapy STEROID RESISTANT: Fail to respond to corticosteroid therapy within 8 wks

Management of Nephrotic Syndrome ALTERNATIVE THERAPY: INDICATIONS: steroid dependent frequent relapsers steroid responsive unwanted effects of steroids CYCLOPHOSPAMIDE: Prolong duration of remission & reduce no. of relapses DOSE: 2-3 mg/kg/24hrs OD For 8-12 wks Alternate day prednisolone often continued

Management of Nephrotic Syndrome METHYLPREDNISOLONE: DOSE:30mg/kg I/V bolus (max 1 gm), first 6 doses on alternate day followed by tapering regimen for 18 months Cyclophosphamide may be added CYCLOSPORIN: DOSE: 3-6mg/kg/24hrs in 12hrly ACE INHIBITORS: adjunct therapy to reduce proteinuria is steroid resistant pts

Complications INFECTIONS: SBP, pneumonia, cellulitis, UTI, disseminated varicella THROMBOEMBOLISM: Renal vein thrombosis, pulmonary embolism, saggital sinus thrombosis of arterial & venous catheters

Complications OTHERS: Deficiencies of coagulation factors 1X, X1,& X11 Reduced levels of vitamin D Acute renal failure Hypertension Malnutrition Flare up of tuberculosis Steroid & anti-metabolite related toxicity Exacerbation by immunization

Differential Diagnosis Other forms of glomerulonephritis including post streptococcal glomerulonephritis Pyelonephritis Obstructive Uropathies Hemolytic Uremic Syndrome Fever, Exercise, Orthostatic protein urea Renal Failure Congestive cardiac failure Liver failure

Follow-up Blood CP Urine RE Growth parameters General examination Blood Pressure Eye examination RFTs Serum electrolytes BSR

Follow-up Serum calcium X-Ray wrist X-Ray spine Chest X-Ray PT/APTT

Prognosis Children responding to steroid rapidly & have no relapses in first 6 months infrequently relapsing steroid responsiveness, no underlying pathology better outcome in INS children with steroid resistant nephrotic syndrome poor prognosis Mortality rate 1-2 %

Congenital Nephrotic Syndrome Infants who develop nephrotic syndrome within first 3 months of life ETIOLOGY: Finish type congenital nephrotic syndrome Congenital infections HIV/HBV Diffused mesengial sclerosis Drash syndrome Minimal change disease Focal segmental glomerulosclerosis

Congenital Nephrotic Syndrome CLINICAL FEATURES Massive proteinuria ( alpha fetoprotein) Large placenta marked edema prematurity respiratory distress separation of cranial sutures Recurrent infections

Congenital Nephrotic Syndrome TREATMENT: ACE inhibitors + Indomethacin + unilateral neprectomy B/L nephrectomy chronic dialysis & kidney transplant no role of steroid or immunosuppressive agents PROGNOSIS: Poor Progressive renal failure Death by 5 yrs age

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