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Childhood nephrotic syndrome:
Diagnosis and management
Dr
Overview
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Nephrotic syndrome in children
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Introduction, definition
Clinical presentation
Investigations
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Referral to a paediatric nephrologist
Management
Conclusions (Practice points)
Introduction
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Nephrotic syndrome (NS)
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Commonest glomerular disease affecting children
Frequently encountered in general paediatrics
Characterised by
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Significant proteinuria (early morning urine protein to
creatinine ratio > 200mg/mmol) leading to
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Hypoalbuminaemia (plasma albumin of < 25g/l)
Paediatrics and child health 2010;20(1):36-42
Introduction
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NS defined by the clinical triad of
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Oedema
Nephrotic range proteinuria and
Hypoalbuminaemia
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Typically accompanied by
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Dyslipidaemia with elevated plasma cholesterol and
triglycerides
Paediatrics and child health 2010;20(1):36-42
Introduction
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NS can be
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Congenital disease
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Congenital or acquired
May be due to a genetic mutation or secondary to a
congenital infection
Acquired disease
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More common and is usually idiopathic
Categorised according to the response to corticosteroid
treatment as
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Either steroid sensitive or steroid resistant disease
Paediatrics and child health 2010;20(1):36-42
Introduction
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Acquired nephrotic syndrome
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Idiopathic (primary) or Secondary (table hereunder)
Paediatrics and child health 2010;20(1):36-42
Clinical presentation
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History
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Typically children present because of oedema
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Initially in a peri-orbital distribution and many children are initially
diagnosed with an allergic reaction
the lower limbs and genital area swollen later in the day as extracellular
fluid accumulates and edema develops in the dependent areas.
Often history of a preceding viral infection
The duration of symptoms variable and a past history of atopic
disease is present in 30-60% of children
The vaccination history and previous varicella infection should be
noted
About 3% of children will have an affected parent or sibling and
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If there is a family history the disease is likely to follow a very similar
pattern
Paediatrics and child health 2010;20(1):36-42
Clinical presentation
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History
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Often upper respiratory tract infection and, with
onset of oedema, children will be
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Lethargic
Irritable and have
Poor appetite, and may have
Diarrhoea and
Abdominal pain
Paediatrics and child health 2010;20(1):36-42
Clinical presentation
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Examination
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Document
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Height
Weight
Blood pressure,
Capillary refill time,
Heart rate
Evidence of pleural effusions, ascites, peripheral, scrotal or sacral
oedema.
The assessment of intravascular volume is important
since
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Hypovolaemia is a common finding and is the leading
cause of mortality and morbidity in these children
Paediatrics and child health 2010;20(1):36-42
Clinical presentation
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Examination
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Document the following; height, weight, blood pressure, capillary
refill time, heart rate, evidence of pleural effusions, ascites,
peripheral, scrotal or sacral oedema.
The assessment of intravascular volume is important since
hypovolaemia is a common finding and is the leading cause
of mortality and morbidity in these children
The following are recognised markers of hypovolaemia:
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capillary refill time >2 seconds,
toe-core temperature gap >2C, hypotension,
persistent tachycardia and abdominal pain.
Since assessment of hypovolaemia can be difficult a urinary sodium
can be useful with a urine Na <10mmol/l being indicative of severe
hypovolaemia
Paediatrics and child health 2010;20(1):36-42
Clinical presentation
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Differential diagnoses
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At presentation it is important to consider the
differential diagnosis of a child presenting with
oedema. These include
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Acute nephritis (hypertension, oliguria, oedema) or
Renal failure (abnormal plasma creatinine) and
Non-renal causes of oedema such as
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Protein losing enteropathy,
Severe cardiac failure,
Chronic liver disease
Paediatrics and child health 2010;20(1):36-42
NS: Investigations
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The purpose of investigations in NS is
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(1) to confirm the clinical diagnosis;
(2) to seek a possible cause;
(3) to assess renal function; and
(4) to identify biochemical disorders related to the
nephrotic state
Paediatrics and child health 2010;20(1):36-42
NS: Investigations
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Children presenting with typical features of NS will
require minimal investigations
Paediatrics and child health 2008;18(8):369-374
NS: Investigations
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The finding of heavy proteinuria (3–4+) on
dipstick and oedema in a child usually means
a diagnosis of NS
Proteinuria needs to be quantified as the
protein: creatinine ratio or per litre of urine
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Twenty-four hour urine collections are
impractical and unnecessary in most children
with NS; instead proteinuria is usually measured
on first morning spot voids
Paediatrics and child health 2008;18(8):369-374
NS: Investigations
Some relevant
laboratory findings
Paediatrics and child health 2008;18(8):369-374
NS: Investigations
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Indications for kidney biopsy
Revised guidelines for management of steroid-sensitive nephrotic syndrome.
Indian J Nephrol 2008;18:31-9
Referral to a paediatric nephrologist
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Most children with MCNS will respond to steroids and not
require a renal biopsy at presentation\
However, if any of the following features are present, there is
the possibility of an alternative diagnosis (less likely to
respond to steroid therapy)and children should be referred to
a paediatric nephrologist:
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Age <1yr or>12yr
Hypertension
Renal impairment
Macroscopic haematuria
Decreased C3 complement
Rash or arthropathy
Primary steroid resistance (failure to go into initial remission with
60mg/m2 steroids for 28 days)
Referral to a paediatric nephrologist
Revised guidelines for management of steroid-sensitive nephrotic syndrome.
Indian J Nephrol 2008;18:31-9
Referral to a paediatric nephrologist
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Microscopic haematuria may be present in up
to 25% of children with steroid-sensitive NS
and should not be a contraindication to
empirical steroid therapy
Some important clinical questions
1.
Estimation of dry weight.
Is the child’s weight known prior to onset of NS?
How much oedema has the child? 1 kg = 1 L? 3 kg
= 3 L? Or more?
2.
Is the child euvolaemic or hypovolaemic?
This simple question can be difficult to answer
clinically. Methods of assessing circulating volume
are listed in Table in next slide.
Some important clinical questions
Some important clinical questions
3. Does this child need volume expansion?
4. Does this child need diuretics or ACE
inhibitors?
5. Does this child need antibiotic prophylaxis?
Complications
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Before the introduction of appropriate medical
treatment as many as 30% of patients died from NS
Complications of NS include:
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Hypovolaemia
Infection
Thrombosis
With careful modern management most children
should expect
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Not to experience hypovolaemia, thrombosis or serious
infection
Paediatrics and child health 2010;20(1):36-42
Management
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All children presenting with their first episode
of NS should be admitted to hospital for
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Diagnostic assessment
Nursing and medical management, and
Parental education
We will first cover
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General management and then the use of
prednisolone or equivalent
Paediatrics and child health 2010;20(1):36-42
Management
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Routine nursing management includes:
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Semi-quantification of urine protein losses (dipsticking all
urine specimens)
Daily weighing
Pulse and blood pressure monitoring
Prevention of infection and appropriate isolation
Careful fluid balance with recording of oral/parenteral
input and measurement of urine output
Parental information, education, support and reassurance
Maintaining child mobility and morale
Management
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Fluid balance, hypovolaemia and blood pressure
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A ‘no added salt’ diet is appropriate measure
If hypovolaemia is present it should be promptly corrected
with administration of 10–20 ml/kg of 4.5% albumin
Diuretics are used in some cases to help control the
oedema until remission begins, e.g. frusemide at 2
mg/kg/24 h
The use of diuretics should be reviewed on a daily basis
and the patient’s electrolytes should be checked regularly
Management
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Fluid balance, hypovolaemia and blood pressure
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Twenty per cent albumin in combination with diuretics is
used in centres to relieve severe symptomatic oedema:
0.5–1.0 g/kg of 20% albumin can be given slowly over 4–
6 h and 0.5–1 mg/kg of frusemide given at the end or mid
way through the infusion
Rapid administration should be avoided to prevent
intravascular volume overload
Twenty per cent albumin should never be used to correct
low serum albumin levels
Management
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Fluid balance, hypovolaemia and blood pressure
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Hypotension is a sign of severe hypovolaemia and should
be quickly addressed
Hypertension may also occur in the acute phase
Persistence of hypertension in the absence of
hypovolaemia warrants referral to a paediatric
nephrologist
Management of edema in patients with
nephrotic syndrome
Patients requiring high-dose frusemide or
addition of other diuretics should be under
close supervision, preferably in a hospital
Monitoring of serum electrolytes is necessary
in all patients receiving diuretics
Patients showing hypokalemia require
potassium supplements or coadministration of
spironolactone. The medications are reduced
stepwise once diuresis ensues.
*Management of hypovolemia consists of
rapid infusion of normal saline at a dose of
15-20 ml/kg over 20-30 min; this may be
repeated if clinical features of hypovolemia
persist. Infusion of 5% albumin (10-15 ml/kg)
or 20% albumin (0.5-1 g/kg) may be used in
subjects who do not respond despite two
boluses of saline
Revised guidelines for management of steroid-sensitive nephrotic syndrome.
Indian J Nephrol 2008;18:31-9
Management
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Infection
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Streptococcus pneumoniae and Gram-negative
organisms are the commonest pathogens causing
possible peritonitis, septicaemia and cellulitis
Prophylactic oral phenoxymethylpenicillin (12.5
mg/kg twice daily) administration is
recommended while the child is oedematous and
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Any suspected infection should be promptly treated
with broad-spectrum antibiotics while awaiting
culture
Clinical features and management of
infections
Revised guidelines for management of steroid-sensitive nephrotic syndrome.
Indian J Nephrol 2008;18:31-9
Management
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Mobilization
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Bed rest may increase the risk of venous thrombosis
Encouraged to mobilize as normal
Diet
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As mentioned above, a ‘no added salt’ diet is advisable in
view of the salt and water overload
No evidence for use of a high protein diet
Encouraged to have a normal healthy diet
Management
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Parent information
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Parents need a clear explanation of the diagnosis
of NS, its implications for the future and the
importance of compliance with medication.
Side effects of medications must also be clearly
explained.
Families should be provided with written
information
Management
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Parent information
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Parents need to be taught how to do urinalysis for home
testing.
They should keep a clear record of daily urinalysis and
medications given
It is important that parents know to contact the
appropriate medical staff in the case of a relapse,
intercurrent illness or exposure to varicella infection
(when nonimmune)
Management
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Immunization
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Live vaccines should not be given to immunosuppressed
children
Children with steroid-sensitive nephrotic syndrome are
considered immunosuppressed if they have received daily
steroids for greater than 1 week in the previous 3 months
A live vaccine can however be given if the child is on a
low dose alternate day regimen
Management
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Corticosteroid therapy
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The International Study of Kidney Disease in
Children (ISKDC) demonstrated that in MCNS
the majority of children will respond to steroids
with 95% of children going into complete
remission following an 8 week course of high
dose steroids
Paediatrics and child health 2010;20(1):36-42
Definitions related to NS
Revised guidelines for management of steroid-sensitive nephrotic syndrome.
Indian J Nephrol 2008;18:31-9
Definitions related to NS
Paediatrics and child health 2010;20(1):36-42
Management
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ISKDC regimen of steroids – gold standard
for three decades
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An eight week course of oral steroids
(prednisolone) starting at
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60mg/m2 daily for 4 weeks followed by
40mg/m2 on alternate days for the next 4 weeks
Paediatrics and child health 2010;20(1):36-42
Paediatrics and child health 2010;20(1):36-42
Revised guidelines for management of steroid-sensitive nephrotic syndrome.
Indian J Nephrol 2008;18:31-9
Management
Management
Management
Guidelines:Management of Steroid Resistant Nephrotic Syndrome
Indian society of pediatric nephrology
Indian Pediatrics. 2009; 46(1): 35-47
Management
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In view of lack of consensus regarding the
most appropriate therapy, the Expert Group
accepts that the choice of initial treatment
shall continue to depend on the preference of
the physician and the cost of medications
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There is a lack of consensus on the most
appropriate first line therapy for children with
SRNS, with many of the regimens extrapolated
from studies in adults.
Guidelines:Management of Steroid Resistant Nephrotic Syndrome
Indian society of pediatric nephrology
Indian Pediatrics. 2009; 46(1): 35-47
Management
Management
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The wide range of options available for the
pharmacotherapeutic management of NS and the
lack of evidence about the comparative efficacy and
safety of the different therapeutic strategies, make its
positioning rather difficult
Therefore each hospital needs to draw up protocols
based not only on the small amount of evidence
available, but also on the
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Authorized indications, availability of the drugs, clinical
experience, associated costs, and patient preferences with
regard to the duration of treatment, incidence and type of
adverse effects
Management
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Development of new randomized controlled trials
should be encouraged and setting up national plans
for the treatment of this pathology might be a good
approach for this problem
Pediatrics 2009;124;747-757
Management
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The vast majority of children with MCD will
outgrow NS with normal kidney function
In the interim,
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Paediatricians need appropriately to care for these
children, support their parents, and ensure that NS
does not metamorphose into the ‘neurotic
syndrome’
Conclusions