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Childhood Nephrotic Syndrome

April 2026

Learning outcomes

At the end of this article, the reader should be able to:

Describe the pathophysiology, clinical features, and diagnosis of childhood nephrotic syndrome;
Understand first-line and supportive management, including steroid responsiveness categories;
Recognise red-flag presentations requiring urgent referral;
Recognise potential complications and key safety issues for pharmacists; and
Appreciate the practical role of the pharmacist in supporting patient care in hospital and community pharmacy.

Childhood Nephrotic Syndrome (NS) is a kidney condition characterised by:

Too much protein in the urine (proteinuria);
Low levels of the protein albumin in the blood (hypoalbuminemia);
Swelling in parts of the body (oedema); and
High levels of cholesterol and other lipids (fats) in the blood (hyperlipidaemia).

Children’s Health Ireland (CHI) estimates approximately 50 children will be diagnosed with NS in Ireland annually.

In children, it is the most common glomerular disorder encountered, with significant short and long-term implications if there is delayed or late diagnosis and treatment. NS can present at any age but is most frequently diagnosed in children aged two to five years old, affecting twice as many boys as girls.

The underlying cause is increased permeability in the glomeruli (filters) of the kidneys, allowing plasma proteins, particularly albumin, to leak into the urine. This leakage lowers the concentration of albumin in the bloodstream, resulting in proteinuria. The resulting hypoalbuminemia reduces the blood’s oncotic pressure, causing fluid to shift from the intravascular space into the tissues, leading to oedema.

To understand the impact of NS on the physiology of a paediatric patient, Table 1 presents a summary of some of the kidney’s functions in the body.

Table 1: Important functions of the kidneys

Remove waste and extra water	Kidneys are the body’s filter. They clean the blood and make urine.
Produce erythropoietin	Erythropoietin is required to make red blood cells.
Balance minerals	Kidneys regulate the level of sodium, calcium, and potassium in the blood.
Control blood pressure	Kidneys help regulate blood pressure.
Support strong bones	Kidneys activate vitamin D in the body.

Clinical features

Children with NS commonly present with:

Generalised oedema, especially puffy eyes in the morning. It can also present as abdominal ascites, limb swelling due to fluid seeping from the blood into the tissues;
Proteinuria — dipstick 3+ to 4+;
Foamy urine from protein loss; and
Fatigue, poor appetite, weight gain from fluid retention.

NS in children is often classified by response to corticosteroids:

Steroid-Sensitive (SSNS) or Minimal Change (MCNS): Remission achieved with steroids;
Steroid-Dependent (SDNS): Relapses when steroid dose reduced; and
Steroid-Resistant (SRNS): No remission with steroid induction.

90 per cent of NS is idiopathic and the most common histological diagnosis in children is SSNS/MCNS. It can occur secondary to infections (for example, hepatitis), medications (most commonly NSAIDS, for example, ibuprofen, indomethacin) and some medicines used to treat mood disorders such as Lithium, or systemic disease such as lupus, malignancy or cardiac failure. Congenital nephrotic syndrome is a separate disease and is caused by inherited genetic defects.

Diagnosis and investigations

Diagnosis is based on clinical symptoms with supportive investigations:

Urinalysis: Proteinuria by dipstick and confirmation by first morning protein: creatinine ratio;
Blood tests: Urea/creatinine, electrolytes, liver function tests including albumin, full blood count;
Specific testing for atypical features (ANA, ANCA, complement C3/C4) when systemic disease is suspected; and
Imaging (renal ultrasound) if diagnosis unclear or complications present.

Renal biopsy is not routinely required at first presentation unless atypical features or steroid resistance is evident.

Management

First episode

Treatment: Corticosteroids are first-line therapy. Prednisolone induces remission in most cases of SSNS. Early remission typically occurs within a few weeks of appropriate therapy:

A high-dose daily induction regimen — initially 60mg/m² daily for four weeks (maximum 60mg);
Reduce to 40mg/m² on alternate days for four weeks;
Then a taper over four to six weeks as directed by a paediatric Nephrologist;
Children who do not enter remission/do not respond to therapy after four weeks of daily steroid therapy should be evaluated as possible steroid-resistant nephrotic syndrome (SRNS).

Other considerations: It is essential to review the patient’s vaccination history to ensure they are fully up-to-date. These patients are at a significantly higher risk of severe complications from common childhood infections. Therefore, maintaining current immunisations is a critical priority alongside treating the underlying cause of the nephrotic syndrome.

Managing relapses

Relapse is common in childhood NS, with almost 70 per cent of children experiencing a relapse, which can have multiple causes including infection. It is most identified by a urine dipstick reading of 3+ or 4+ protein for more than three consecutive days. Re-introducing a defined steroid course as outlined above typically leads to remission. Some children may require steroid-sparing immunosuppressants listed below if disease is frequently relapsing or steroid-dependent:

Calcineurin inhibitors (Cyclosporin, Tacrolimus);
Cyclophosphamide;
Mycophenolate mofetil; and
Choice of medication is guided by a Paediatric Nephrologist, and genetic assessment is considered for steroid-resistant cases.

Other common adjunct therapies include:

Gastric protection if patient is symptomatic of gastric irritation;
ACE inhibitors/ARBs to reduce proteinuria and control blood pressure in NS patients where hypertension has developed;
Diuretics for significant oedema under specialist guidance;
Statins for patients with persistent severe hyperlipidaemia; and
Vitamin D supplementation for frequently relapsing nephrotic syndrome or in the presence of Vitamin D deficiency.

Vitamin D deficiency is common in children with NS. Vitamin D is heavily protein bound and is excreted via the urine with its carrier protein (Vitamin-D-binding Protein). In addition, for Vitamin D to work it must be converted into its active form (1,25(OH)₂D) in the kidneys. When the kidneys are inflamed or damaged due to NS, their ability to perform this conversion is impaired. Furthermore, corticosteroid therapy depletes vitamin D reserves. Alfacalcidol is also considered in SRNS, especially if the patient has reduced kidney function or is at high-risk of developing Secondary Hyperparathyroidism. This is assessed on a case-by-case basis.

Complications and monitoring

Infection

Children with nephrotic syndrome are at increased risk of bacterial infections, particularly, peritonitis, cellulitis, UTI or pneumonia. Please see counselling guidelines below.

Thrombosis

NS increases the risk of venous and arterial thrombosis. Pharmacists should counsel caregivers on sudden limb pain/swelling, shortness of breath, or neurological changes; emergency referral is mandatory.

Steroid adverse effects

While steroids are a corner stone of NS treatment, caregivers should be counselled on the potential long-term side effects of extended steroid use:

Growth suppression;
Hypertension;
Osteopenia/osteoporosis;
Metabolic changes (glucose intolerance); and
Behavioural changes.

Education on side-effect recognition and gradual tapering plans is important. Regular monitoring and multidisciplinary care reduces morbidity.

Acute Kidney Injury (AKI)

May arise due to hypovolaemia, infection, or medication side effects;
Requires urgent referral and aggressive management of fluid status and underlying causes; and
See medicines management and monitoring below for further information.

Childhood NS in community pharmacy — considerations

Although NS is relatively rare, community pharmacists are likely to encounter these patients and their families repeatedly after hospital discharge, particularly during relapses. Children with NS often require long courses of corticosteroids, dose adjustments and close monitoring for complications. This places community pharmacists in a key position to reinforce safe use of medicines, detect early warning signs, and support families navigating a complex condition. Pharmacists can act as an accessible and trusted point of contact, helping to reduce medication errors, prevent avoidable complications, and improve adherence. They can encourage continuity of care by advising families to use one pharmacy where possible for consistent medication reviews.

Medicines management

Children with nephrotic syndrome are at higher risk of AKI, electrolyte disturbances, infection and drug toxicity, particularly during relapses, dehydration, intercurrent illness, or when oedematous. Community pharmacists play a key role in preventing avoidable harm. It is important to be vigilant about medications that are commonly associated with AKI in children.

Medicines to avoid or require monitoring in children with Nephrotic Syndrome

1. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) – AVOID

Examples: Ibuprofen, naproxen, diclofenac. Why avoid — ↓ Renal perfusion:

Reduce renal prostaglandins → decreased renal blood flow;
Can precipitate AKI, especially during dehydration or relapse; and
May worsen oedema and hypertension.

Community pharmacy action:

Recommend paracetamol as first-line analgesic/antipyretic; and
Refer to GP if pain or fever persists

Immunosuppressants

These are commonly prescribed under specialist supervision for patients who are steroid-resistant. Examples: Tacrolimus, ciclosporin. Community pharmacy action:

Watch for drug–drug interactions (for example, macrolides, azoles);
Reinforce regular blood monitoring compliance as these agents require more frequent specialist monitoring;
Familiarise yourself with sign and symptoms of potential toxicity with these agents; and
Advise urgent referral to consultant if the patient displays any of these signs or symptoms.

3. Over-the-counter and complementary products — AVOID unless approved

Examples:

Herbal supplements;
High-dose vitamin A; and
Creatine or protein supplements.

Risk:

Unregulated nephrotoxicity; and
Increased solute load on kidneys.

Community pharmacy action:

Actively ask about OTC use; and
Advise ‘check first’ before starting any supplements (remember that many patients will be on Vitamin D as part of their treatment. Be mindful of multivitamin combinations).

Key counselling points

1. Safe steroid use

Confirm dosing accuracy at every dispensing: steroid doses are often weight-based and may change frequently during tapering;
Provide written instructions if there is a complicated dosing tapering schedule;
Explain the importance of adherence and not stopping steroids abruptly due to risk of adrenal suppression;
Encourage giving steroids with food and earlier in the day to reduce gastrointestinal upset and sleep disturbance; and
Reinforce expected side-effects (increased appetite, mood changes, facial rounding) to reduce anxiety and improve adherence.

2. Infection awareness and safety netting

Advise caregivers to seek urgent medical attention for fever ≥38°C, lethargy, or signs of infection;
Remind families that children on steroids are more vulnerable to infections, even if symptoms appear mild; and
Highlight the importance of avoiding NSAIDs unless advised by a doctor, as they may worsen kidney function.

3. Reinforce vaccination guidance

Ensure that pneumococcal, meningococcal, haemophilus influenza type B and annual influenza vaccines are up to date. The live flu nasal vaccine should be used where possible to optimise protection against flu. The IM injection should be used if the child is on high-dose steroids or immunosuppressants;
Nephrotic syndrome is variably associated with hyposplenia. See NIAC guidelines for nephrotic patients as they are vaccinated as per asplenic patients;
Remind caregivers that live vaccines should be delayed during high-dose steroid or immunosuppressive treatment; and
Review NIAC Chapter 3 Immunisation of Immunocompromised Persons and the relevant NIAC vaccination chapter if managing a vaccination query for a NS patient (hiqa.ie > Reports and Publications > Immunisation Guidelines for Ireland).

4. Encourage monitoring at home

Reinforce the importance of regular urine dipstick testing, especially during illness or if experiencing oedema;
Encourage caregivers to monitor:
- Sudden weight gain;
- Increasing oedema; and
- Changes in urine output.
Suggest keeping an up-to-date medication list and symptom diary, which can be invaluable during reviews.