Overview of

Nephrotic
Syndrome (NS)
BY CJ Lau
3 June 2009

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 Background
 Is not a disease but a collection of symptoms
 Not be to confused with nephritic syndrome
 Also known as nephrosis
 Characterized by :
1. Proteinuria
2. Hypoalbuminemia
3. Hyperlipidemia
4. edema

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 Classification

Nephrotic syndrome

Primary/idiopathic NS Secondary
(gromerular (etiology extrinsic to the
diseases intrinsic to kidney)
the kidney)
-Minimal change nephrotic syndrome (MCNS)-Hepatitis B & C
-Focal segmental glomerulosclerosis (FSGS) -Diabetes mellitus
-Membranous nephropathy (MN) -Syphilis
-Systemic Lupus Erythematous
-drug exposure (eg. lithium &
mercury)

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 Pathophysiology
 proteinuria- concentration of heparan sulfate(-
ve charged) in the basement membrane is
lower in NS patients, filtration of plasma
protein(-ve charged) through glomerular
membrane is prevented by a negatively
charged filtration barriers
 Hypoalbuminemia-glomerular capillary
permeability to albumin is selectively
increased, leads to hyperalbuminurea and
eventually hypoalbuminemia

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 Pathophysiology
 Edema- hypoalbuminemia lowers the
plasma colloid osmotic pressure,
causing transcapillary filtration of
water and the development of edema
 Hyperlipidemia- hypoproteinemia
stimulates generalized protein
synthesis in liver including lipoprotein.

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 Epidemiology
 9th leading cause of death in Sarawak general hospital
in 2006 (3.41% of total death)
 Children at any age and adults can get it, but usually
children between the age of 1 ½ -4 are more prone
 Boys are twice more susceptible than girls
 In adults, male-female prevalence is approximately
equal

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 Clinical Presentation
 Increasing edema over a few days or weeks,
lethargy, poor appetite and occasional
abdominal pain
 Edema is the predominant feature, initially
develops around eyes & lower extremities,
becomes generalized and leads to weight gain
 Decline in urine output and frothy urine
 Hematuria and hypertension are unusual

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 Diagnosis
 First morning urine protein/creatinine value
greater than 2-3mg/mg or 24hours urine protein
level of more than 40mg/m2/hr
 Serum albumin level less than 2.5g/dL (normal
3.5-5g/dL)
 Elevated total cholesterol, low density
lipoprotein (LDL) and triglycerides.
Normal or low high density lipoprotein (HDL).
 Check creatinin and urea level to evaluate renal
function

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 Treatment
 Renal biopsy – not indicated for INS in children
prior to starting corticosteroid therapy. It is
indicated for steroid resistant NS (not achieving
remission despite 4weeks of adequate
corticosteroid therapy). Other indication would
depends on presence of features to suggest
other renal diseases such as persistent
hypertension and haematuria. Decision is up to
attending pediatrician in consultation with the
pediatric nephrologists.

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Management of edematous
state
 Antibiotics- penicillin V 125mg BD (1-5years
old),250mg BD (6-12years old) and 500mg BD
(>12years old) is recommended during relapse
particularly with gross edema.
 Diet-A normal protein diet with adequate calories
is recommended. No added salt to the diet during
the edematous state.
 Fluid restriction- Not usually recommended except
in chronic edematous state.
 Diuretics- Frusemide is usually not necessary in
steroid responsive NS but if require should be used
with caution as it can precipitate hypovolaemia.

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Management of edematous
state
 Human albumin (20-25%) at 0.5-1.0g/kg can be
used in symptomatic edematous state together
with IV frusemide at 1-2mg/kg to produce a
diuresis. Urine output and blood pressure should be
closely monitored.
 Human albumin at 0.5-1.0g/kg of 5%, 20% or 25%
(whichever is available) over one hour should be
given in those suspected to have hypovolaemia. Do
not give frusemide in this instant.

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 Corticosteroids
 Effective in inducing remission of NS
 Prednisolone dosage orally for children-
60mg/m2/day or 2mg/kg/day in divided dose 3-
4times (maximum of 80mg/day) for 4 weeks.
Followed by 40mg/m2/dose or 1-
1.5mgmg/kg/alternate day for 4weeks. Reduce
prednisolone dose by 25% monthly over next
4months.
 Monitor blood pressure, blood glucose.
 95% of children will achieve remission defined
as urine dipstick in trace or nil for 3
consecutive days within 28days .
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 Treatment of relapse
 Relapse is defined by urine albumin excretion
more than 40mg/m2/hour, dipstick of 2+ or more
for 3 consecutive days.
 Prednisolone 60mg/m2/day until remission then
40mg/m2/dose for 4 weeks and off.
 Frequent relapse -2 or more relapses within 6
months of initial response.
 Treatment-Prednisolone 60mg/m2/day till nil
albumin in urine for 3 days then
40mg/m2/alternate mornings for 4weeks. Taper
prednisolone dose every 2weeks and keep on as
low alternate day dose as possible for 6 months.

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 Management of steroid
dependent
 Defined as 2 consecutive relapses
ocurring during the period of steroid
taper or 14 days of its cessation.
 If a child is not steroid toxic
(eg.cushing syndrome), reinduce with
steroids and maintain on as low dose
of alternate day prednisolone as
possible as possible.
 If child is steroid toxic, consider
cyclophosphomide therapy.
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 Steroid resistant NS
 Refer for renal biopsy- specific
treatment will depend on the
histopathology.

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 Cyclophosphamide
 An alkylating agent, also possess potent
immunosuppressive activity.
 Indicated for the treatment of steroid dependent nephrotic
syndrome with sigh of steroid toxicity.
 Dose- Oral: 2-3mg/kg/day everyday for up to 12weeks
 Monitoring parameters- Complete blood count with blood
count, serum creatinine
 Adverse effects-hemorrhagic cystitis (drink plenty of
fluids, avoid taking drug at night), leucopenia

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 Complication of NS
 Infection - due to low IgG level and impaired T-cell functions in INS
patients. Medications used to treat NS (corticosteroids) further
suppress immune system. Patients are at risk of infection,
especially with Streptococcus Pneumonia. Patients infected with
varicella should be treated with acyclovir.
 Thromboembolism- renal vein thrombosis, deep vein thrombosis,
and pulmonary thrombosis are common due to increase platelet
activation and aggregation, decreased antithrombin III, protein C
& S which leads to hypercoagulable state in INS. Following
tromboembolism, warfarin is often prescribed for a period of 6
months. Some practitioners advocate the use of low dose aspirin
in chronic NS patients, however, adequate clinical trials
examining the use of aspirin have not been performed.

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 Patient education
 Home monitoring of first morning urine protein with
urine dipstick
 Weight should be checked and a home logbook
should be kept (include the steroid dose taken)
 Consult doctor if edema, weight gain, or proteinurea
persist for more than 2days
 Control fluid (urine volume+500ml) and salt intake
 Yearly influenza vaccination and pneumococcal
vaccination (every 5years) are recommended.

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 References
 http://emedicine.medscape.com/article/982920-overview
 http://www.myhealth.gov.my/myhealth/bm/dewasa_content.jsp?lang=dewas
 http://www.kidney.org/Atoz/atozItem.cfm?id=53 (national kidney
foudation)
 http://www.hkl.gov.my/content/hfacts/death2007.htm
 Drug information Handbook, Lexi-Comp
 http://mpaeds.org.my/PaediatricProtocols/46.%20Nephrotic%20Syndrome.pd
http://mpaeds.org.my/PaediatricProtocols/46.%20Nephrotic%20Syndrome.p
 Consensus of statement – Management of idiopathic nephrotic
syndrome in childhood. Ministry of Health. Academy of Medicine
Malaysia 1999.
 Hodson EM, Knight JF, Willis NS, Craig JC. Corticosteroid therapy for
nephrotic syndrome in children. The Cochrane library, Issue
1,2003.Oxford
 Durkan A, Hodson E, Willis N, Craig J. Non corticosteroid treatment for
nephrotic syndrome in children. The Cochrane library, Issue 1, 2003,
Oxford.

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