Nephrotic Syndrome

Prof. Imran IqbalDepartment of Paediatrics

Children’s Hospital & Institute of Child Health, Multan, Pakistan

Nephrotic Syndrome

Nephrotic Syndrome ?Usual Presenting feature is Oedema

D/D of Oedema

Nephrotic Syndrome

Acute Glomerulonephritis

Congestive Heart Failure

Kwashiorkor

Chronic Liver Disease

Protein Losing Enteropathy

Angioedema

OPD Urine Examination

• Protien = 2 + OR 3 +

• Urine protein/creatinineratio > 2

• Nephrotic Syndrome likely

Proteinuria

Spot urine

Trace = 15mg/dl

+ = 30mg/dl

++ = 100mg/dl

+++ = 300mg/dl

++++ = 2000mg/dl

Dipstick

Boiling

P/C ratio

Heavy proteinuria ( > 40mg/m2 /hour

or > 50mg/kg/day)

Hypoalbuminaemia (<2.5g/dl)

Oedema

Hyperlipidaemia (>220mg/dl)

Nephrotic Syndrome

Typical Clinical Features

• Age 2-6 years

• Boys 70 %

• Facial Puffiness / marked edema

• Mild Diarrhea

• Oliguria

• Blood Pressure normal or low

• Anorexia

Other PRESENTATIONS of NS

• GENERALIZED BODY SWELLING- EDEMA, OLIGURIA

• Abdominal pain

• Acute kidney injury

• Infections

• Shock

• Thrombo-embolism

• Hypertension

• Routine urinalysis

EXAMINATION

Clinical Assessment of Circulating Volume

•Toe Temp.

•Capillary Refill time

• B.P

•Pulse Rate, Volume

Extent of Edema

Infections

Systemic Examination

Weight, Height, Ideal weight for Height, Surface area

COMPLICATIONS

• Gross edema

• Hypovolemia

• Infections – peritonitis, cellulitis, UTI

• Pneumonia

• Tuberculosis

• Arterial / venous thrombosis

Atypical Clinical Features

• Age < 1 year or > 10 years

• Hematuria

• Hypertension

• Azotemia

Nephrotic Syndrome in Children

Congenital/Infantile NS

Primary Secondary

•Finnish Type

•DMS

•Deny –Drash Syndrome

•MCNS

•FSGS

•MN

•Galloway-Mowat

Syndrome

•Nail-Petella Syndrome

• Congenital Infections

• HIV

• Malaria

• SLE

Childhood NS

Secondary

• SLE

• HSP

•Hep B

•Others

Primary

(Idiopathic)

• MCD

• FSGS

• DMP

• MPGN

• MN

Nephrotic Syndrome in Children

• Primary Nephrotic Syndrome - 95%

• Minimal Change Disease - 80 %

CAUSES OF SECONDARY Nephrotic Syndrome

• SLE

• HSP

• Hepatitis B, C

• HIV

• Malaria

• Lymphoma

• Drugs (NSAIDS)

SLE

Secondary NS - Causes

• Lupus nephritis (LN)

• HSP nephritis (HSPN)

• Hepatitis C nephritis - MPGN

• Hepatitis B nephritis – MN

• Malaria

• HIV nephritis

• Lymphoma

• Drugs

Minimal Change Disease

• Genetic factors

• T – cell activation

• Cytokines – IL 4 & IL 13

MCD - pathology

Albuminuria

PATHOPHYSIOLOGYUnder-fill Hypothesis

Heavy Albuminuria

Hypoalbuminaema

Reduced Plasma Oncotic Pressure Continuing Salt& Water Intake

OEDEMA

Renal Salt & Water retention

HypovolaemiaShift of fluid from

plasma to interstitium

Reduced GFR

Increased proximal tubular salt &water reabsorption

Activation of the RAAS

Release of ADH

Inhibition of atrial natriuretic peptide

Labs for Nephrotic Syndrome

INITIAL INVESTIGATIONS

• Urine Exam

• Serum albumin

• Urea , Creatinine

• Lipid profile

• Na, K, Ca,

• CBC

• PT, APTT

Subsequent Investigations

• HBsAg

• HCV antibody

• ASO titre

• USG abdomen

• Tuberculin test

• X ray Chest

• C3 , C4

• Anti ds DNA antibodies

Management of Nephrotic Syndrome

• Patient COUNSELING

• Disease

• Urine Examination

• Medicines

• Complications

• Immunisations

MONITORING

• Daily home monitoring of proteinuria(PU) by dipsticks or boiling method and keeping diary

• Follow up every 4 weeks- check weight, BP, PU, edema, side effects of steroids and other medicines

• Height – every 6 months

Immunisations

• Avoid live vaccines

• Give Pneumococcal vaccine

Pneumococcal conjugate vaccine

Pneumococcal polysaccharide vaccine

SUPPORTIVE TREATMENT

Diet Hypovolemia Diuretics Mucosal protectives Antihypertensives Infections

Gross Edema

DIURETICS- WHEN TO USE ? Very cautious and judicious use when :

• Generalized anasarca

• Massive ascities or pleural effusion causing respiratory difficulty

• Massive scrotal swelling with imminent skin rupture

• Concomitant albumin infusions are required to mobilize edema

• Persistent hypertension

DIURETICS-RISKS

• Intavascular volume depletion

• Thromboembolism

• Acute kidney injury

• Severe electrolyte imbalance

• Steroid Sensitive Nephrotic Syndrome: 90%

• Steroid Resistant Nephrotic Syndrome: 10%

Primary/ Idiopathic NS

Steroid Induction of Remission therapy

• Prednisolone 60 mg / m2 for 4 wks

( usual remission time 7 – 10 days )

• If no remission:

Continue same dose for another 4 wks

OR

MethylPrednisolone IV 30 mg / m2 alternate day for 3 doses

Continuation Steroid therapy

If remission achieved:

• Prednisolone 40 mg / m2 alternate day for 4 wks

• Reduce dose by 5 – 10 mg every 4 weeks

• Stop treatment by 3 – 6 mo

Relapses in Nephrotic Syndrome

• Relapses 40 – 70 %

Treatment of Relapse

• Prednisolone 60 mg / m2 till remission

• Reduce dose by 5 – 10 mg every 4 weeks

Terminology Remission = urine albumin free for 3 days

Relapse = urine albumin 3+ for 3 days

Frequent Relapser = > 2 relapses in 6 mo or

> 3 relapses in 12 mo

Steroid Dependant = relapse within 14 days of reducing steroid dose

Steroid Resistant = No response to initial steroid therapy in 4 – 8 weeks

Types of NEPHROTIC SYNDROME Steroid Sensitive NS (SSNS)

– Non Relapsing NS (NRNS)

– Infrequently Relapsing NS (IRNS)

– Frequently Relapsing NS (FRNS)

– Steroid Dependant NS (SDNS)

Steroid Resistant NS (SRNS)Atypical NSSecondary NS

Treatment of Frequent Relapses

• Prednisolone 10 – 15 mg / m2 in Alternate day doses continued for 1 – 2 years

• Cyclophosphamide 2mg /kg for 12 weeks

• Mycophenolate Mofetil 30 mg / kg / day

Adverse effects of steroid therapy

• Infections

• Cushingoid appearance

• Emotional problems

• Hypertension

• Acid peptic disease

• Osteoporosis

• Impaired glucose tolerence

• Growth retardation

Iatrogenic Cushing’s Syndrome

MANAGEMENT OF SSNS

First Episode of NS

Trial of Steroids

Response

Withdraw Steroids over 6 months Relapse Repeat short Steroid course

Infrequent relapse

Frequent relapses Intermittent short steroid

courses

or Steroid dependency

No Relapse, discharge

Alternate day Steroids

Steroids well toleratedContd. AD Steroids

Steroids not well tolerated Consider Alternatives

Renal Biopsy

• Steroid Resistance • Age < 1 year >10 years

• Prolonged mild proteinuria

• Macroscopic haematuria

• Marked persistent HTN

• Persistent renal insufficiency

• low C3 or C4

• Cyclosporine therapy

Prognosis of SSNS

• Relapses decreased after few years

• In some relapsing patients , Relapses may continue upto 14 – 20 years

• Renal insufficiency is rare

Predictors of prolonged course

• Early onset of disease

• Severity of proteinuria

• Frequent Relapses

150 Beds Extension (New Block)