nephrotic syndrome presented by dr. huma daniel. characteristic features heavy proteinuria >...

Nephrotic SyndromeNephrotic Syndrome

Presented byPresented byDr. Huma DanielDr. 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

Permeability of glom.cap.memb. Proteinuria

Intravascular vol

ADH Renal perfusionpressure

WaterReabsorptnInCollectingducts

Actv. reininAng. ald. sys

Tubular reabsorp.Of Na

Hypoalbuminemia

Hepatic protein synthesis Plasma oncoticpressure

Hyperlipidemia Transudation of fluidfrom intravascularcomp. To interstialspace

Edema

Pathophysiology

IDIOPATHIC NEPHROTIC SYNDROME

MINIMAL CHANGE DISEASE FOCALSEGMENTALSCLEROSIS

AGE 2-6yrs 2-10yrsSEX 2:1 male 1:3:1 maleHEMATURIA 10-20% 60-80%HYPERTENSION 10% 20%RENAL FAILURE No progression 10yrsASSOCIATIONS Allergy & Hodgkin NoneSERUM CREATININ Inc. in 15-30% Inc. in 20-40%IMMUNOGENETIC HLA-B8, B12 NoneLIGHT MICROSCOPE Normal Focal sclerosisIMMUNOFLOUR Negative IgM & C3 in lesionsELECTRON MICRO Foot process fusion Foot process fusionSTEROID RESPONSE 90% 15-20%

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:

Normal• TOTAL CALCIUM:

Decreased

Diagnosis

• OTHERS:• VITRAL SEROLOGY:

– 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:– R/O Tb before starting steroids

• RENAL BIOPSY• 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– Alternative therapy

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

Thank You