ephrotic syndrome in children. for under graduates

2. Dr. Muhammad Sajjad Sabir
MBBS, DCH, MCPS, FCPS
Assistant Professor of Paediatrics

3.  Manifestation of glomerular disease,
characterized by nephrotic range proteinuria
and a triad of clinical findings associated with
large urinary losses of protein :
hypoalbuminaemia , edema and
hyperlipidemia

4. Edema
Heavy proteinuria > 40mg/m2/hr
Hypoalbuminemia <2.5g/dl
Hyperlipidema >250mg/dl

5. 15 times more common in children than
adults
2 – 7 cases per 100,000 children per year
(Global)
Incidence South Asia 16/100,000 children
Most common= 1.5-6 year
boys : girls--- 2:1 ratio

6.  Defined as
 protein excretion of > 40 mg/m2
/hr
 First morning protein : creatinine ratio of > 2-3 : 1
- Nelson Textbook of Paediatrics, Vol 2, 19th
Edition, page 1801

7. Idiopathic or Primary
Genetic
Secondary

8.  Minimal Change disease ( >80 % )
 Mesangial proliferation
 Focal segmental Glomerulosclerosis
 Membranous Nephropathy
 Membranoproliferative glomerulonephritis
- Nelson Textbook of Paediatrics, Vol 2, 19th
Edition, page 1804

9. Finnish type Congenital Nephrotic Syndrome
Focal Segmental Glomerulosclerosis
Diffuse Mesangial Sclerosis
Denys-Drash Syndrome
- Nelson Textbook of Paediatrics, Vol 2, 19th
edition, page 1802, table 521-1

10.  Congenital
 Oligomeganephronia
 Infectious
 Hepatitis (B,C) , HIV-1, Malaria, Syphilis, Toxoplasmosis
 Inflammatory
 Glomerulonephritis
 Immunological
 Castleman Disease, Kimura Disease, Bee sting, Food allergens
 Neoplastic
 Lymphoma, Leukemia
 Traumatic ( Drug induced )
 Penicillamine, Gold, NSAIDS, Pamidronate, Mercury, Lithium

11. Permeability of glom.cap.memb. Proteinuria
Intravascular vol
ADH
Renal perfusion
pressure
Water
Reabsorptn
In
Collecting
ducts
Actv. reinin
Ang. ald. sys
Tubular reabsorp.
Of Na
Hypoalbuminemia
Hepatic protein synthesis Plasma oncotic
pressure
Hyperlipidemia Transudation of fluid
from intravascular
comp. To interstial
space
Edema

12. Preceding flu-like illness
General health
(anorexia, weight gain ,lethargy)
Edema
Urinary symptoms
(hematuria, oliguria)
Infection, diarrhea, abd. pain
Drug intake
Past history

13. Edema
 Mild to start with – peri orbital puffiness, lower
extremities
 Progression to generalized edema, ascites, pleural
effusion, genital edema
Decreased urine output
 Anorexia, Irritability, Abdominal pain and diarrhoea
 Absence of Hypertension Gross hematuria
 Vital & BP
 Height & weight for age
 Anemia - Nelson Textbook of Paediatrics, Vol 2, 19th
Edition, page 1802
Clinical Features-Examination

14. CLINICAL FEATURES Minimal Change
Nephrotic Syndrome
Focal Segmental
Glomerulosclerosis
Membranous
Nephropathy
Age ( yr ) 2 - 6 2 - 10 40 - 50
Sex ( M : F ) 2 : 1 1.3 : 1 2 : 1
Nephrotic
Syndrome
100 % 90 % 80 %
Asymptomatic
proteinuria
0 10 % 20 %
Hematuria 10 – 20 % 60 – 80 % 60 %
Hypertension 10 % 20 % early infrequent
Rate of
progression to
renal failure
Non
progressive
10 yrs 50 % in 10 – 20
yrs
Associated
Conditions
Usually none None Renal vein
thrombosis, SLE,
Hepatitis B

15. Periorbital puffiness

16.  Protein losing enteropathy
 Hepatic failure
 Heart failure
 Acute/Chronic Glomerulonephritis
 Protein Malnutrition
• < 1 year old
• Family history of nephrotic Syndrome
• Hypertension
• Pulmonary edema
• Gross hematuria
• Extrarenal findings
• < 1 year old
• Family history of nephrotic Syndrome
• Hypertension
• Pulmonary edema
• Gross hematuria
• Extrarenal findings

17. URINE ANALYSIS
 PROTEINURIA: 3+ Or 4+
 MICROSCOPIC HEMATURIA: 20%
 PUS CELLS: underlying UTI
 CELLULAR CASTS: not in minimal
change disease
 24HRS URINARY PROTEIN
EXCRETION:
Children : >40mg/m2/hr
 URINARY spot PROTEIN : CREATININE
> 2.0
(Spot UPC ratio > 2.0)
trace /nil (10-20mg/dl)
+ (30mg/dl)
++ (100mg/dl)
+++(300mg/dl)
++++(1000-2000mg/dl)

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

19. VITRAL SEROLOGY:
 HBV associated with membranous nephritis
BLOOD COUNTS:
 Hb, TLC & DLC Normal
 ESR raised
X-RAY CHEST:
 R/O pulmonary TB
 R/O pleural effusion

20.  MANTOUX TEST:
 R/O TB before starting steroids
 RENAL BIOPSY
 ANA: R/O SLE
• Age below 12 months
• Gross or persistent microscopic hematuria
• Low blood C3
• Hypertension
• Impaired renal Function
• Failure of steroid therapy
Indications for Renal biopsyIndications for Renal biopsy

21.  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

22. Management

23.  DIETARY ADVICE:
 A balanced diet adequate in proteins and
calories is recommended
 foods high in sodium avoided
 High protein diet
 Edema no added salt
 Treatment of infections
 Parent Education
 Can attend school
 Can participate in physical activities as tolerated

24. If significant edema
 Diuretics + Aldosterone antagonist
( Fursemide, spironolactone )
 Salt restriction
 DIURETICS INDICATIONS:
 Severe symptomatic edema
 Steroid toxicity or steroid contraindicated
Q.Best diuretic in Nephrotic Syndrome?

25. ROLE OF INTRAVENOUS ALBUMIN
INDICATIONS:
 Signs of hypovolemia
 Sever oedema
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/dose (I/V)

26. CORTICOSTEROID THERAPY:
 DOSAGE & ADMINISTRATION:(after a -ve PPD test)
 Prednisolone 60mg/m2
/day (max 80mg) single
daily dose {or 2-3 dd} for 6 wks consecutively
 After the initial 6-wk course, prednisone dose tapered
to 40 mg/m2
/day given every other day as a
single daily dose for at least 4 wk.
 Alternate-day dose then slowly
tapered→discontinued over next 1-2 mo

27. REPONSE TO STEROID:80-90% of children
respond within 3 wk
 10% respond by first week
 70% by second week
 85% by third week
 92% by forth week
 Response means clinical remission, diuresis,
and urine trace or negative for protein for 3
consecutive days
 Who respond to prednisone therapy do so
within the first 5 wk of treatment.

28. STEROID DEPENDENT: Patients who relapse while on
alternate-day steroid therapy or within 28 days of
completing a successful course of prednisone therapy
FREQUENT RELAPSERS: Patients who respond well
to prednisone therapy but relapse ≥4 times in a 12-mo
period
INFREQUENT RELAPSERS :3 or less relapses per yr
STEROID RESISTANT: Fail to respond to corticosteroid
therapy within 8 wks
Children who continue to have proteinuria (2+ or greater)
Diagnostic renal biopsy should be performed

29.  Relapses should be treated with 60 mg/m2
/day
(80 mg daily max) in a single am dose until the
child enters remission (urine trace or negative
for protein for 3 consecutive days)
 The prednisone dose is then changed to
alternate-day dosing as noted with initial
therapy, and gradually tapered over 4-8 wk.
Ghai Essential Paediatrics,8th
edition, page 479

30. ALTERNATIVE THERAPY:
 INDICATIONS:
 steroid dependent
 frequent relapsers
 steroid responsive
 unwanted effects of steroids

31. Alternate Day prednisolone
Steroid sparing agents
 Levamisole ( 2 – 2.5 mg/kg )
 Cyclophosphamide ( 2 – 2.5 mg/kg/day)
 Mycophenolate Mofetil ( 20 – 25 mg/kg/day )
 Cyclosporin ( 4 – 5 mg/kg/day )
 Tacrolimus (0.1 – 0.2 mg/kg/day )
 Rituximab ( 375mg/m2
IV once a week )
Ghai Essential Paediatrics,8th
edition, page 479, 480

32. INFECTIONS:
 SBP
 Pneumonia
 Cellulitis
 UTI
 disseminated varicella
THROMBOEMBOLISM:
 Renal vein thrombosis
 pulmonary embolism
 saggital sinus thrombosis
OTHERS:
 Acute renal failure
 Hypertension
 Malnutrition
 Flare up of tuberculosis
 Steroid & drug related
toxicity

33. Blood CP
Urine RE
Growth parameters
General examination
Blood Pressure
Eye examination
RFTs
Serum electrolytes
BSR
Serum calcium
X-Ray wrist
X-Ray spine
Chest X-Ray
PT/APTT

34. Steroid Responsive NS : Good prognosis
( MCNS )
Steroid Resistant NS : Poor prognosis
( FSGS )
Mortality rate 1-2 %
- Nelson Textbook of Paediatrics, Vol 2, 19th
Edition, page 1806

35.  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

36. 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 if untreated