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NEPHROTIC SYNDROME
THE SWOLLEN CHILD
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DEFINITION
It is a clinical syndrome of:
1. Heavy proteinuria >1 g/m2/day
2. Hypoproteinemia serum albumin < 2.5 g/dL
Protein:Creatinine > 200mg/mmol
3. Oedema
4. Hypercholestrolnemia > 250 mg/dL
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EPIDEMIOLOGY
WestUncommon: 3 new cases per 100,000 child
population
AsianHigher incidence: 16 new cases per 100,000
childpopulation
MalaysiaNo available data, it is thought to have higherincidence
than in the west
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CLASSIFICATION
Primary or Idiopathic Secondary
no known aetiology
Minimal change disease (MCD)Focal Segmental
Glomerulosclerosis
(FSGS)Membranous nephropathycongenital nephrotic syndrome
Systemic disease- SLE- HSP- DM
Infections- Post-infectious GN- Hepatitis B- Syphilis-
Malaria
Drugs
Toxins and allergen- bee sting- food allergy
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Minimal Change Disease most common (70-80%) M:F = 2:1 < 7
years old
steroid-sensitive nephrotic syndrome do not progress to renal
failure often precipitated by respiratory infections Features:
age between 1 and 10 years
no macroscopic haematuria normal blood pressure normal
complement levels normal renal function.
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FSGS Membranousnephropathy
Congenital NS
10% of NS in childhood
progress from MCD /
separate entity
circulating factor thatincreases glomerularpermeability to
albumin
1% of NS in childhood
common in adolescent
and children with- systemic infection- hep B- syphilis- malaria-
toxoplasmosis
- drug therapy
heamaturia present
clinical Ns presentsduring the first 3 monthsof life2 types-
Finish- heterogeneous group
of abnormalities
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PATHOPHYSIOLOGY
Primary disorder:
Loss of glomerularBM sialoprotein
Loss of normalnegative charge
Increase glomerular
permeability
Massive proteinuria
Decrease serumprotein
Decrease plasmaoncotic pres.
Fluid shift from
vascular to interstitial
Contraction of plasmavolume
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Edema:
- under fill theory: hypoalbuminemia
- over fill theory:tubular NaCl reabsorptionsecondary to RAAS
intravascular expansion fluid shift following pressure gradient
Hypercholesterolemia
- hypopratenemia hepatic lipoprotein synthesis serum lipid
(cholesterol, lipoprotein) lipid
metabolism
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COMPLICATION
Infection Spontaneous bacterial peritonitis, cellulitis,
bacteriemia (S.pneumoniae, E.coli) Steroid and immunosuppressant
toxicity
Hypovolaemia abdominal pain and may feel faint, cold
peripheries, poor pulse volume, hypotension,
and haemoconcentration. A low urinary sodium (
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CLINICAL MANIFESTATION
Sudden onset of dependent pitting oedema
- periorbital
- scrotal or vulva
- ankle or leg Weight gain
Ascites
- abdominal pain
- malaise Diarrhea(dt intestinal oedema)
Respiratory distress (dt pulm. oedema)
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HISTORY TAKING
First time or relapse???
History of edema noted on awakening in the morning or sudden
swelling?? Distribution Colour changes Initiating factor? (bee
sting) Painful??
Weight gain (edema)
Respiratory distress Breathlessness
Diarrhea
Urine: frothy
Pass medical and drug history: recent illness, allergies,
asthma
Family history
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PHYSICAL EXAMINATION
Assessment of hydration status identifies fluid imbalances
(dehydration,overhydration)
Blood pressure: hypertension
Henoch-Schnlein purpura (purpura)
Systemic lupus erythematosus (malar rash)
Ralesheard on lung auscultation suggest extravascular fluid from
overload orhypoalbuminemia
Palpation and percussion of the abdomen may reveal ascites or
masses
Liver enlargement is present in several multisystem diseases
(systemic lupuserythematosus, infections, polycystic disease) and
in glomerulosclerosis
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DIFFERENTIAL DIAGNOSIS
Main ddx:
1. Anaphylaxis
2. Cellulitis (orbital,periorbital)
3. Angioedema
4. Nephrotic synd.
5. Other causes of hypoalbuminaemia
Transient proteinuria Postural orthostatic proteinuria
Glomerular abnormalities
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INVESTIGATIONS
Diagnostic studies:
1. Proteinuria +1> on 2/3 random urine sample (Dipstick)
2. P:C (> 200mg/mmol) (early morning)
3. Serum lipid
4. C3 level ( sensitive n specific if other than MCD)
Full blood count: HCT, WBC
Renal profile: normal in MCD
Serum albumin:
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Other investigations
complement levels: decrease suggest other thn MCD
Antistreptolysin O titre and throat swab
Hepatitis B antigen
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DEFINITION FOR DX & TX OF IDIOPATHIC NS
REMISSION:
Urinary protein excretion < 4 mg/m2/hour or urine dipstix
nil/trace for 3 consecutive days.
RELAPSE:
Urinary protein excretion > 40 mg/m2/hour or urine dipstix ++
or more for 3 consecutive days.
FREQUENT RELAPSES:Two or more relapses within 6 months of
initial response or four or more relapses within any 12 month
period.
STEROID DEPENDENCE:
Two consecutive relapses occurring during the period of steroid
taper or within 14 days of its cessation.
STEROID SENTITIVE:
Normalization of proteinuria within 4 weeks after start of
standard initial therapy with daily oralpredinisolone
STEROID RESISTANCE:
Failure to achieve remission in spite of 4 weeks of standard
prednisolone therapy.
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MANAGEMENT
STEROID SENSITIVE
Prednisolone regime for initial dx: 60 mg/m2/day (max 80mg/day)
for 4 weeks
40 mg/m2/48 hr (max 60mg/dose) for further 4 weeks Prednisolone
regime for relapses:
60 mg/m2/day (max 80mg/day) until remission
40 mg/m2/48 hr for 4 weeks
Frequent relapse or steroid dependent:
Long term low dose prednisolone for 3-6 months
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SCHEMA OF TREATMENT OF IDIOPATHIC NEPHROTIC SYNDROME
1. Nephrotic Syndrome
Initial Diagnosis
Prednisolone 60 mg/m2/day (max 80/day) for 4 week
Response No Response
Prednisolone 40 mg/m2/48 hours for 4 weeks
Renal Biopsy
*Discontinue *Steroid taper at 25% monthly over 4 months
2. RelapsePrednisolone 60 mg/m2/day (max 80 mg/day) till
remission,
then 40 mg/m2/48 hours for 4 weeks and discontinue.
3. Frequent Relapses
Reinduce as for (2) above, then taper and keep low dose
alternate day
prednisolone at 0.1 - 0.5 mg/kg/dose for 6 months.
4. Relapse on prednisolone
As for (3) if not steroid toxic,
consider cyclophosphamide (cumulative dose 168 mg/kg) if steroid
toxic.
5. Relapses post cyclophosphamide
As for (2) and (3) if not steroid toxic.
If steroid toxic, refer paediatric nephrologist to consider
a). second course cyclophosphamide or
b). cyclosporine therapy.
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STEROID RESISTANT
Symptomatic therapy:diuretic
blood pressure control : ACEi (captopril, enalapril),
angiotensin IIreceptor antagonist
hyperlipidaemia
Immunosuppressive therapy:Steroids
cyclophosphamideCyclosporin, tacrolimus, mycophenolate
mofetil
Indications for renal biopsyA renal biopsy is also NOT required
prior to cytotoxic therapySteroid resistant nephrotic syndrome
Secondary NSCongenital NS
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Steroid toxicity
Stunting of growth
Cataracts
Striae
Severe cushingoid featuresobehavioural changes, a rounded face,
central obesity and thetendency to bruise more easily,
hirsutism
Osteoporosis
Proximal myopathy
Recurrent infection dt low immunity
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MANAGEMENT
Mx of oedematous state Bed rest to be avoided as there is a
tendency of
hrpercoagulability
Dietary advice: no added salt, normal protein with adequate
calories Prophylactic antibiotics: oral penicillin particularly
in during
relapse with gross oedema
Hypovolaemia: infuse salt poor albumin or 5% albumin,
plasma protein derivatives or human plasma Diuretics
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Mx complication: Infection: parenteral penicillin and a third
generation
cephalosporin (in primary peritonitis)
If exposed to chickenpox and measles varicella-zoster
immunoglobulin (VZIG) should be given within 72 hours
afterexposure to chickenpox / single dose of
intravenousimmunoglobulin.
Thrombosis :Warfarin, low-dose aspirin, and dipyridamole all
have been used to minimize the risk of clots.
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URINE ALBUMIN MONITORING
It is advocated that monitoring of urine albumin
excretion be done regularly either at home withurinary dipstix
or at the nearest health centre.
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EDUCATION
Education:Parents and school teachers should be provided with
information
regarding the disease which includes:
1. Advice and precaution of infection
2. Danger of sudden steroid withdrawal (adrenal crisis)
3. Immunisation:
While the child is on corticosteroid treatment and within 6
weeksafter its cessation, only killed vaccines may be safely
beadministered to the child. Live vaccines can be administered
6weeks after cessation of corticosteroid therapy
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PROGNOSIS
Idiopathic NS
Steroid sensitive (90%)
Frequentrelapses/S.dependent (50%)
Infrequent relapses (33%)
No relapses (25%)
Steroid resistant (10%)
ESRF
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NUR AMIRA BINTI MOHD ASRI
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CASE SCENARIOA 7 year old Malay boy was admitted 3 days ago with
thechief complaints of facial puffiness and passing smokey
and frothy urinefor 1 week. The facial puffiness
initiallystarted off as periorbital oedema which then progressedto
involve the entire face within a week. Urinary outputwas also
decreased. He also complaint of fever for one
week which was of low grade, intermittent with no chillsand
rigor. There is also presence of an erythematousitchy skin lesion
on his right elbow which was firstnoticed 2 weeks back. There is no
history of sore throat,flu, blood transfusion, nausea, and
vomiting, rashes,dyspnoea and chest pain. General examinations
revealedpallor, high blood pressure of 139/96 mmHg, and
anerythmatous scaly circular skin lesion on his right elbow.Urine
biochemistry revealed protein 3+, RBC 4+. Blood
urea was raised to 500 umol/L.
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NEPHRITIC SYNDROME
It is a clinical complex, usually acute onset,characterized
by:
oedema eg facial
puffinessMicroscopic/macroscopic haematuria (tea-coloured
urine)
Oligouria (decreased urineoutput)
hypertension
Azotemia/uremia (excess ureain urine)
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The lesions that cause nephritic syndrome have incommon
proliferation of cells within in glomeruli,accompanied by a
leukocytic infiltration.
This inflammatory reaction injures the capillarywalls,
permitting escape of RBC into theurine(hematuria) , and induced
hemodynamicschanges that lead to a reduction in GFRwhich
aremanifested clinically by oligouria, reciprocal fluid
retention and azotemia Hypertension is the result of the fluid
retention by
kidney secretion of renin.
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GLOMERULONEPHRITIS
NEPHROTICSYNDROME
NEPHRITICSYNDROME
Acute poststreptococcalGN
lgA nephropathy
Henoch-schnleinpurpura
SLE
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POSTSTREPTOCOCCAL AGN
The commonest cause of nephritic syndrome Usually followed a
nephritogenic streptococcal
pharyngitis or impetigo with a strain of group Abeta-hemolytic
streptococci
Immune-mediated inflammation Occurs most frequently in children
2 to 12 years old
Boys are frequently affected
This is diagnosed by evidence of a recent streptococcal
infection (culture of the organism, raised ASOT) andlow
complement C3 levels, that return to normal after6-8 weeks
Long term prognosis is good
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Epidemiology of post acute strep GN
121 of the 124 nephritis patients hadpoststreptococcal
infection.
(Department of paediatrics, HUSM, July 1987-June 1988)
Globally-incidence has decreased in the past 3
decades
Most commonly-sporadic
Despite that,epidemic cases in some poor and rural
communities
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pathogenesis
Throat/skin infection by gp A betahemolytic streptococci
(serotype 12, 4 and1)
Antibodies to streptococcus(antistreptolysin O) are formed in
thecirculation
Antigen-antibody circulating immunecomplexes are subsequently
depositedalong the glomerular basementmembrane (GBM)
l i f i
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Streptococcal infection
Immune complex formation +deposited inGBM
Complement system
activated
Immune injuries
Cellular proliferation
Capillary lumen narrowed
Glomerular blood flow decreased
oligouria GFR low Distal sodium reabsorption
Retention of water and sodium
Blood volume increased
Low serumcomplement
GBM fracture
hematuria
proteinuria
Edema and
hypertension
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HENOCH-SCHNLEIN PURPURA
It is a systemic syndrome involvingthe skin (purpuric
rash),gastrointestinal tract (abdominalpain, joints (athritis), and
kidney
The combination of Skin rashes(symmetrical
distributed over thebuttocks,extensor surface ofarms and legs
and the ankles.
Athralgia (knees and ankles)
Periarticular oedema Colicky abdominal pain, GI
petechiae,hematemesis,melaena, intussusception
Glomerulonephritis
Usually occurs between theages of 3-10 years olds
Twice as common in boys peaks during winter months Is often
preceded by an
upper respiratory infection Unknown cause however it
is postulated that geneticpredisposition and antigenexposure
increasecirculating lgA levels.
By immunofluorescence andelectron microscopy thefindings may be
similar tothose of IgAN
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Systemic lupus erythematosus (SLE)
Is an autoimmune disease that presents mainly inadolescent girls
and young women(5% in childhoodgirl, rare in children younger than
9 yo, equal genderdistribution in children)
Multisystem disorder of unknown etiologycharacterized by the
production of large amounts ofcirculating antibodies due to loss of
T lymphocytescontrol on B lymphocytes which leads to
autoantibody production Presence of multiple antibodies
including antibodies
to double-stranded DNA .
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Criteria for diagnosis of SLE
signs
Malar rash (butterflyrash)
Photosensitivity
Oral and nasopharyngealulcers
Pleuritis and pericarditis
Non erosive arthritis (more than 2 joints witheffusion and
tenderness.
Investigation data
Protenuria(>500mg/2
4 hrs) or RBC cellularcast in urine
Positive anti-dsDNA
Evidence of presence of
antiphospholipidantibodies
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lgA NEPHROPATHY
Affects children and young adults Begins as an episode of gross
hematuria that occurs within 1 or 2
days of a nonspecific upper respiratory tract infection. Is one
the most common causes of recurrent microscopic or gross
hematuria and is the most common glomerular disease revealed
byrenal biopsy
The pathology hallmark is the deposition of lgA in the mesangium
Prognosis is good in children
immunofluorescence with anti-IgA antibodies deposited in the
mesangium
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Familial nephritis
The commonest familial nephritis isAlportssyndrome
X-linked recessive disorder
Is associated with nerve deafness and ocular defect The mother
may have hematuria
Can progress to end-stage renal failure by early adultlife in
males.
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Basic workup of a child with hematuria
History-age,gender,sosioeconomic status,familyhistory,drug
history
Physical
examination-height,weight,bloodpressure,funduscopy,presence or
absence of abdominalmass,skin
appearance,genitalia,edema,completephysical examination.
Laboratory-urinalysis (includingmicroscopicexamination and RBC
morphology), urine culture,complete blood count (including
platelets), serum
electrolytes, creatinine,calcium, serum complement,random urine
for total protein, creatinine, renalimaging studies.
Nelsonp758
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D A L L I A N A A D I A B T E A B D L A T I F
2 0 0 8 4 0 2 2 9 2
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History
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History
Antedencent hx of streptococcal throat of skininfection-
post-streptococcal GN
Ask about symptoms of swelling-facial,perioral,pedal edema, or
ascites
Symptom of pulmonary edema/ CHF (eg dyspnoeawith exertion,
orthopnoea, SOB)
Gross hematuria (eg dark, rust, coke, tea coloured)
Family hx, other family member with nephritis orrenal failure-
Alport syndrome
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Epistaxis, headache, encephalopathy- severe
hypertension Oligouria
Nonspecific symptoms eg malaise, fever, anorexia,weakness
For tubulointestinal nephritis- try to obtain ahistory of a
known etiology (eg bacterial, viral, drugrelated, metabolic,
other)
TIN, usually hx of polyuria than oliguria
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Investigation
Laboratory
FBC- anemia, leucocytosis
Urinalysis and culture- hematuria, proteinuria,
RBCs cast,other cellular masts, pyuria? Bacteriological an
serology- Anti streptolysin-O
titer (>200IU/mL), Anti-DNAse B, throatswab/skin swab, lupus
serology, serum IgA
Measure complement level- C3
RFT- blood urea, serum creatinine, electrolytes,BUN
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Acute poststreptococcal GGN- low C3, positive ASOTand anti
DNAase B
TIN- hematuria, eosinophilia, sterile pyuria, lowgrade
proteinuria, eosinophiluria, urinary WBc casts
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Imaging
Renal ultrasonography- usually to exclude othercauses of
hypertension and hematuria but usuallynot conducted in real cut
nephritic sydrome
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Histology
light microscopy: lymphocytes, PMN leukocytes
Immunofluoroscene- IgG, IgA, IgM, or complement
Electron- deposit in mesangial, subendothelial, or
subepithelial
P l h i i
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Post-streptococcal nephritis
Urinalysis
ASOT
Low complement C3 levels- return to normal after 3-
4 weeks
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Management
Treat the primary pathology- immunosuppressivemed eg steroids or
cyclophosphamide in lupus
Supportive care- Fluid and electrolyte balance,diuretics, Ca
channel blocker, ACEi, monitor rapiddeterioration in renal
function
Diet- fluid restriction, sodium, potassium restriction,Ca
supplement
Dialysis
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Complication
Complication of severe hypertension (e.g. cerebralhaemorrhage,
seizure, enchepalopathy,stroke, endorgan damage)
Complication of renal failure (e.g. hyperkalemia,fluid overload,
electrolyte abnormality, uremicsymtoms, anemia, abnormal bone
mineralization,sexual dysfunction, poor growth, anorexia)
Complication of primary disease (eg SLE)
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Nephrotic and nephritic
Nephrotic Nephritic
noninflammatory inflammatory
Started from infancy More in the school age group
Glomerular basement changes:
decrease charge selectivity, sizeselctivity, or increase
permeability
Capillary changes
Sudden onset of hematuria (brownurine), RBC , RBC casts, and
WBC,and granular casts present
Massive proteinuria, mainlyalbuminuria (>1g/m2/24 hrs)
mild proteinuria
Hypoalbuminemia (serum albumin
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Nephrotic Nephritic
Edema (dt hypoalbuminemia) Edema (salt and water retention)
Hyperlipidemia (>250 mg/dL) dtincrease lipoprotein
Lipiduria No lipid in the urine
Piss it all away and get fat (edema andhyperlipidemia)
Immune, inflammation, I cant pee, Icant see (HTN)
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