Nephrotic syndrome IN CHILDREN Lecture for MBBS

Nephrotic syndrome IN CHILDREN FOR UNDER GRADUATES

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

4. 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

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

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

7. Defined as
Protein excretion of > 40 mg/m
2
/hr
(>1g/m
2
/24 hr)
Spot Protein : Creatinine > 2-3 : 1
(First morning urine sample)

- Nelson Textbook of Paediatrics, Vol 2, 19
th
Edition, page 1801

8. Idiopathic or Primary
Genetic
Secondary

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

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

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

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

14. Periorbital puffiness

15. Edema
Mild early – periorbital puffiness, lower extremities
Progression to gen. edema, ascites, pleural
effusion, genital edema
Decreased urine output
Anorexia, Irritability, Abdominal pain and diarrhoea
Vital & BP
Height & weight for age
Anemia
- Nelson Textbook of Paediatrics, Vol 2, 19
th
Edition, page 1802
Clinical Features-Examination
 No Hypertension
 No Gross hematuria

16. 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 % earlyInfrequent
Rate of
progression to
renal failure
Non
progressive
10 yrs 50 % in 10 – 20
yrs
Associated
Conditions
Usually noneNone Renal vein
thrombosis, SLE,
Hepatitis B

17. URINE ANALYSIS
PROTEINURIA: 3+ Or 4+
MICROSCOPIC HEMATURIA: 20%
PUS CELLS:underlying UTI
CELLULAR CASTS: not in minimal change
disease
Trace /nil (10-20mg/dl)
+ (30mg/dl)
++ (100mg/dl)
+++(300mg/dl)
++++(1000-2000mg/dl)

18. 24HRS URINARY PROTEIN EXCRETION:
Children : >40mg/m2/hr
(>1g/m
2
/24 hr)
URINARY spot PROTEIN : CREATININE > 2.0
(Spot UPC ratio > 2.0)

19. SERUM
S. CREATININE:Normal
S. CHOLESTROL:↑ >250mg/dl
S. ALBUMIN: <2.5g/dl
C3 & C4: Normal
TOTAL CALCIUM:Decreased

20. 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

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

22. Protein losing enteropathy
Hepatic failure
Heart failure
Acute/Chronic Glomerulonephritis
Protein Malnutrition

23. Other forms of glomerulonephritis
Pyelonephritis
Obstructive Uropathies
Hemolytic Uremic Syndrome
Fever
Exercise
Orthostatic proteinurea
Renal Failure
Congestive cardiac failure
Liver failure

24. Management

25. DIETARY ADVICE:
Balanced diet = adequate proteins & calories
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

26. 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?

27. ROLE OF INTRAVENOUS ALBUMIN
INDICATIONS:
Signs of hypovolemia
Sever oedema
DOSAGE & ADMINISTRATION:
I/V salt poor 25% albumin infusion
0.5-1 gm/kg/dose over 6-12 hrs + I/V
Frusemide 1-2 mg/kg

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

29. Response means
Clinical remission
Diuresis , and
Urine trace or negative for
protein for 3 consecutive days

30. REPONSE TO STEROID:
80-90% children respond within 3 wk
10% respond by first week
70% by second week
85% by third week
92% by forth week
Who respond to prednisone therapy
do so within first 5 wk of treatment

31. 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

32. Relapses should be treated with:
Prednisone 60 mg/m
2
/day (80 mg daily max)
As single am dose
Until child enters remission (urine trace or
negative for protein for 3 consecutive days)
Then prednisone changed to alternate-day
(40 mg/m
2
/day )
Gradually tapered over 4-8 wk

33. ALTERNATIVE THERAPY:
INDICATIONS:
Steroid dependent
Frequent relapsers
Steroid responsive
Unwanted effects of steroids

34. 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/m
2
IV once a week )

35. 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

36. 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

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

38. DEFINITION:
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

39. TREATMENT:
ACE inhibitors + Indomethacin + unilateral neprectomy
B/L nephrectomy →Chronic dialysis & Renal transplant
no role of steroid or immunosuppressive agents
PROGNOSIS:
Poor
Progressive renal failure
Death by 5 yrs age if untreated