Childhood nephrotic syndrome: Diagnosis and management

1
Childhood nephrotic syndrome Diagnosis and
management

• Dr

2
Overview

• Nephrotic syndrome in children
• Introduction, definition
• Clinical presentation
• Investigations
• Referral to a paediatric nephrologist
• Management
• Conclusions (Practice points)

3
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 gt 200mg/mmol) leading
  to
• Hypoalbuminaemia (plasma albumin of lt 25g/l)

Paediatrics and child health 201020(1)36-42
4
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 201020(1)36-42
5
Introduction

• NS can be
• Congenital or acquired
• Congenital disease
• 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 201020(1)36-42
6
Introduction

• Acquired nephrotic syndrome
• Idiopathic (primary) or Secondary (table
  hereunder)

Paediatrics and child health 201020(1)36-42
7
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 201020(1)36-42
8
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 201020(1)36-42
9
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 201020(1)36-42
10
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 gt2 seconds,
• toe-core temperature gap gt2C, hypotension,
• persistent tachycardia and abdominal pain.
• Since assessment of hypovolaemia can be difficult
  a urinary sodium can be useful with a urine Na
  lt10mmol/l being indicative of severe hypovolaemia

Paediatrics and child health 201020(1)36-42
11
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 201020(1)36-42
12
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 201020(1)36-42
13
NS Investigations

• Children presenting with typical features of NS
  will require minimal investigations

Paediatrics and child health 200818(8)369-374
14
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 200818(8)369-374
15
NS Investigations
Some relevant laboratory findings
Paediatrics and child health 200818(8)369-374
16
NS Investigations

• Indications for kidney biopsy

Revised guidelines for management of
steroid-sensitive nephrotic syndrome.
Indian J Nephrol 20081831-9
17
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 lt1yr orgt12yr
• 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)

18
Referral to a paediatric nephrologist
Revised guidelines for management of
steroid-sensitive nephrotic syndrome.
Indian J Nephrol 20081831-9
19
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

20
Some important clinical questions

• 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?
• 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.

21
Some important clinical questions
22
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?

23
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 201020(1)36-42
24
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 201020(1)36-42
25
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

26
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

27
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 46 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

28
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

29
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 20081831-9
30
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

31
Clinical features and management of infections
Revised guidelines for management of
steroid-sensitive nephrotic syndrome.
Indian J Nephrol 20081831-9
32
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

33
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

34
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)

35
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

36
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 201020(1)36-42
37
Definitions related to NS
Revised guidelines for management of
steroid-sensitive nephrotic syndrome.
Indian J Nephrol 20081831-9
38
Definitions related to NS
Paediatrics and child health 201020(1)36-42
39
Management

• ISKDC regimen of steroids gold standard for
  three decades
• An eight week course of oral steroids (prednisolon
  e) starting at
• 60mg/m2 daily for 4 weeks followed by
• 40mg/m2 on alternate days for the next 4 weeks

Paediatrics and child health 201020(1)36-42
40
Paediatrics and child health 201020(1)36-42
41
Revised guidelines for management of
steroid-sensitive nephrotic syndrome.
Indian J Nephrol 20081831-9
42
Management
43
Management
44
Management
GuidelinesManagement of Steroid Resistant
Nephrotic Syndrome Indian society of pediatric
nephrology
Indian Pediatrics. 2009 46(1) 35-47
45
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.

GuidelinesManagement of Steroid Resistant
Nephrotic Syndrome Indian society of pediatric
nephrology
Indian Pediatrics. 2009 46(1) 35-47
46
Management
47
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

48
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

49
Pediatrics 2009124747-757
50
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

51
Conclusions
52
Thank You!