childhood nephrotic syndrome: diagnosis and management dr

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


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


Introduction Acquired nephrotic syndrome

Idiopathic (primary) or Secondary (table hereunder)


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


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


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


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


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


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


NS: Investigations Children presenting with typical features of NS will

require minimal investigations


NS: Investigations 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 Twenty-four hour urine collections are

impractical and unnecessary in most children with NS; instead proteinuria is usually measured on first morning spot voids


NS: Investigations

Some relevant laboratory findings


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


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 questions1. 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 questions3. 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


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


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 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


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


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 hospitalMonitoring of serum electrolytes is necessary in all patients receiving diureticsPatients 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


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


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


Definitions related to NS


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


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

childhood nephrotic syndrome: diagnosis and management dr

Documents

child health

capillary refill time

assessment of hypovolaemia

acquiredcongenital disease

past history of atopic

sacral oedema

common finding

family history