Nephrotic Syndrome
Presented by
Dr. Huma Daniel
Characteristic Features
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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.
Hypoalbuminemia
Intravascular vol
ADH
Proteinuria
Renal perfusion
pressure
Hepatic protein synthesis
Hyperlipidemia
Water
Reabsorptn
In
Collecting
ducts
Actv. reinin
Ang. ald. sys
Tubular reabsorp.
Of Na
Plasma oncotic
pressure
Transudation of fluid
from intravascular
comp. To interstial
space
Edema
Pathophysiology
IDIOPATHIC NEPHROTIC SYNDROME
AGE
SEX
HEMATURIA
HYPERTENSION
RENAL FAILURE
ASSOCIATIONS
SERUM CREATININ
IMMUNOGENETIC
LIGHT MICROSCOPE
IMMUNOFLOUR
ELECTRON MICRO
STEROID RESPONSE
MINIMAL CHANGE DISEASE FOCAL
SEGMENTAL
SCLEROSIS
2-6yrs
2-10yrs
2:1 male
1:3:1 male
10-20%
60-80%
10%
20%
No progression
10yrs
Allergy & Hodgkin
None
Inc. in 15-30%
Inc. in 20-40%
HLA-B8, B12
None
Normal
Focal sclerosis
Negative
IgM & C3 in lesions
Foot process fusion
Foot process fusion
90%
15-20%
SECONDARY NEPHROTIC SYNDROME
MEMBRANOUS
NEPHROPATY
MEMBRANOPROLIFERATIVE
TYPE 1
5-15yrs
Male: female
80%
TYPE 2
5-15yrs
Male: female
80%
AGE
SEX
HEMATURIA
10-20yrs
2:1 male
60%
HYPERTENSION
RENAL FAILURE
ASSOCIATIONS
LAB FINDING
Infrequent
10-20 yrs
CA,SLE,HBV
35%
10-20yrs
None
LCI, C4, C3-9
LIGHT
MICROSCOPE
IMMUNOFLOUR
ELECTRON MICRO
STEROID
RESPONSE
Thick GBM, Spikes
Thick GBM
35%
5-15yrs
Lipodystrophy
C1,C4,N/ C3,
C9L
Lobulation
Fine IgG, C3
SE deposits
Slow progression
Granular IgG, C3
Mesangial & SE
Not Established
C3 ONLY
Dense deposits
Not Established
Clinical Features
• HISTORY
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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
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EXAMINAITON
Vital & bp
Height & weight for age
Anemia
Periorbital puffiness
Lymphadenopathy
Pleural effusion, ascites
Ankle, sacral, genital edema
Clinical Features
Diagnosis
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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
Nephrotic Syndrome
Biopsy if no response
Daily prednisolone 60mg/m2
max 80mg for 28 days
Minimal
change
Remission
Treatment as
appropriate
Alternate day prednisolone
40mg/m2 max 60mg
No relapses
Other
pathology
Frequent
relapses
SCHEME FOR MANAGEMENT OF
CHILDREN WITH NEPHROTIC
SYNDROME
Frequent relapses
Alternate day prednisolone
Weaned off over 6 months
Relapses on prednisolone
>0.5mg/kg/alt.days
Add levamisole 2.5mg/kg/alt.days 612 months
Relapse on prednisolone >0.5mg/kg/alt.day for
steroid side effects
SCHEME FOR MANAGEMENT OF
CHILDREN WITH NEPHROTIC
SYNDROME
Relapse on prednisolone >0.5mg/kg/alt.day for steroid
side effects
Cyclophosphamide 3mg/kg/day for 8 wks
Relapse on prednisolone >0.5mg/kg/alt.days
Cycloporin 5mg/kg/day for 1-3 yrs
Relapse on cycloporin
Other immunosuppressive agents
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
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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:
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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:
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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
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Blood CP
Urine RE
Growth parameters
General examination
Blood Pressure
Eye examination
RFTs
Serum electrolytes
BSR
Follow-up
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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
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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