Childhood nephrotic syndrome:

Diagnosis and management

Dr

Overview

Nephrotic syndrome in children

Introduction, definition
Clinical presentation
Investigations

Referral to a paediatric nephrologist

Management
Conclusions (Practice points)

Introduction

Nephrotic syndrome (NS)

Commonest glomerular disease affecting children

Frequently encountered in general paediatrics
Characterised by

Significant proteinuria (early morning urine protein to

creatinine ratio > 200mg/mmol) leading to

Hypoalbuminaemia (plasma albumin of < 25g/l)

Paediatrics and child health 2010;20(1):36-42

Introduction

NS defined by the clinical triad of

Oedema
Nephrotic range proteinuria and
Hypoalbuminaemia

Typically accompanied by

Dyslipidaemia with elevated plasma cholesterol and

triglycerides

Paediatrics and child health 2010;20(1):36-42

Introduction

NS can be

Congenital disease

Congenital or acquired
May be due to a genetic mutation or secondary to a
congenital infection

Acquired disease

More common and is usually idiopathic

Categorised according to the response to corticosteroid
treatment as

Either steroid sensitive or steroid resistant disease

Paediatrics and child health 2010;20(1):36-42

Introduction

Acquired nephrotic syndrome

Idiopathic (primary) or Secondary (table hereunder)

Paediatrics and child health 2010;20(1):36-42

Clinical presentation

History

Typically children present because of oedema

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

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

History

Often upper respiratory tract infection and, with

onset of oedema, children will be

Lethargic
Irritable and have
Poor appetite, and may have
Diarrhoea and
Abdominal pain

Paediatrics and child health 2010;20(1):36-42

Clinical presentation

Examination

Document

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
Paediatrics and child health 2010;20(1):36-42

Clinical presentation

Examination

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:

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

Differential diagnoses

At presentation it is important to consider the

differential diagnosis of a child presenting with
oedema. These include

Acute nephritis (hypertension, oliguria, oedema) or

Renal failure (abnormal plasma creatinine) and
Non-renal causes of oedema such as

Protein losing enteropathy,

Severe cardiac failure,
Chronic liver disease
Paediatrics and child health 2010;20(1):36-42

NS: Investigations

The purpose of investigations in NS is

(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

Children presenting with typical features of NS will

require minimal investigations

Paediatrics and child health 2008;18(8):369-374

NS: Investigations

The finding of heavy proteinuria (34+) 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

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

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

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:

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

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 childs 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

Before the introduction of appropriate medical

treatment as many as 30% of patients died from NS
Complications of NS include:

Hypovolaemia
Infection
Thrombosis

With careful modern management most children

should expect

Not to experience hypovolaemia, thrombosis or serious

infection
Paediatrics and child health 2010;20(1):36-42

Management

All children presenting with their first episode

of NS should be admitted to hospital for

Diagnostic assessment
Nursing and medical management, and
Parental education

We will first cover

General management and then the use of

prednisolone or equivalent
Paediatrics and child health 2010;20(1):36-42

Management

Routine nursing management includes:

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

Fluid balance, hypovolaemia and blood pressure

A no added salt diet is appropriate measure

If hypovolaemia is present it should be promptly
corrected with administration of 1020 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 patients electrolytes should be checked regularly

Management

Fluid balance, hypovolaemia and blood pressure

Twenty per cent albumin in combination with diuretics is

used in centres to relieve severe symptomatic oedema:
0.51.0 g/kg of 20% albumin can be given slowly over 4
6 h and 0.51 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

Fluid balance, hypovolaemia and blood pressure

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

Infection

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

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

Mobilization

Bed rest may increase the risk of venous thrombosis

Encouraged to mobilize as normal

Diet

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

Parent information

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

Parent information

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

Immunization

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

Corticosteroid therapy

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

ISKDC regimen of steroids gold standard

for three decades

An eight week course of oral steroids

(prednisolone) starting at

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

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

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

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

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

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

The vast majority of children with MCD will

outgrow NS with normal kidney function
In the interim,

Paediatricians need appropriately to care for these

children, support their parents, and ensure that
NS does not metamorphose into the neurotic
syndrome

Conclusions