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Nephrotic syndrome in children

What's new

The Kidney Disease: Improving Global Outcomes Foundation (KDIGO) has published a new guideline for the management of nephrotic syndrome in children. Kidney biopsy is not routinely indicated at initial presentation, as prognosis is primarily determined by response to glucocorticoids and relapse frequency during the first year; biopsy is reserved for steroid-resistant cases, atypical features, or onset after age 12. Oral glucocorticoids are recommended for either 8 weeks (4 weeks daily followed by 4 weeks alternate-day) or 12 weeks (6 weeks daily followed by 6 weeks alternate-day) as initial therapy. Glucocorticoid-sparing agents such as calcineurin inhibitors, cyclophosphamide, MMF, levamisole, and rituximab are recommended in frequently relapsing or steroid-dependent disease, while cyclosporine and tacrolimus are preferred in steroid-resistant cases. Daily glucocorticoids are not routinely recommended during infections to prevent relapse, but a short course of low-dose daily prednisone or prednisolone may be considered at the onset of an upper respiratory tract infection in selected high-risk patients already on alternate-day therapy. .

Background

Overview

Definition
Nephrotic syndrome is the most common glomerular disease in childhood, characterized by massive proteinuria, hypoalbuminemia, and edema. The majority of pediatric cases are idiopathic and steroid-sensitive, falling under the umbrella of steroid-sensitive nephrotic syndrome.
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Pathophysiology
The pathogenesis involves increased glomerular permeability due to podocyte dysfunction, resulting in severe protein loss, hypoalbuminemia, and compensatory hepatic lipid production. Most children with steroid-sensitive nephrotic syndrome, if biopsied, are found to have minimal change disease, which may show podocyte foot process effacement or mild mesangial proliferation with IgM deposition. Less frequently, FSGS may be present, particularly in steroid-resistant cases. Congenital and infantile-onset nephrotic syndrome, presenting within the first 3 months of life, is typically caused by genetic mutations affecting podocyte proteins and is often steroid-resistant. These forms are associated with poor response to immunosuppressive therapy and a high risk of progression to end-stage kidney disease.
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Epidemiology
Nephrotic syndrome has an incidence ranging from 1.15 to 16.9 per 100,000 children, with variability across ethnic and geographic populations. It primarily affects children between the ages of 2 and 6 years and is more common in males.
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Risk factors
A family history of nephrotic syndrome or other glomerular diseases may increase susceptibility. Environmental triggers such as recent viral infections, particularly upper respiratory tract infections, are frequently reported at disease onset. Genetic mutations affecting podocyte structure and function are more often associated with steroid-resistant forms but may occasionally be present in steroid-sensitive cases.
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Disease course
The clinical course of steroid-sensitive nephrotic syndrome typically begins with edema, often periorbital, and may follow an upper respiratory infection. As the disease progresses, generalized edema may develop, including ascites, pleural effusions, and scrotal or labial swelling. Edema may be accompanied by fatigue, decreased urine output, and nonspecific abdominal discomfort. Around 85% of children achieve remission with standard glucocorticoid therapy within 4-6 weeks. However, 70-80% experience at least one relapse, and up to 50% develop frequent relapses or steroid dependence. Kidney function is preserved in steroid-sensitive nephrotic syndrome when appropriately managed, but prolonged glucocorticoid exposure and second-line therapies can contribute to treatment-related morbidity.
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Prognosis and risk of recurrence
While the disease often resolves spontaneously after puberty, 10-30% of children may have persistent relapses into adulthood, and a small subset (< 5%) may develop secondary steroid resistance with increased risk of progression to kidney failure and post-transplant recurrence.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of nephrotic syndrome in children are prepared by our editorial team based on guidelines from the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2025), the International Pediatric Nephrology Association (IPNA 2023), and the European Reference Network on Rare Kidney Diseases (ERN ERKNet/ESPN 2021).
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Screening and diagnosis

Definitions
As per KDIGO 2025 guidelines:
Use the following definitions in children:
Situation
Guidance
Nephrotic-range proteinuria
Urinary protein-to-creatinine ratio ≥ 200 mg/mmol (2 g/g) in a spot urine sample, or proteinuria ≥ 1,000 mg/m² per day in a 24-hour urine sample, corresponding to 3+ (300-1,000 mg/dL) or 4+ (≥ 1,000 mg/dL) by urine dipstick
Nephrotic syndrome
Nephrotic-range proteinuria and either serum albumin < 30 g/L (3 g/dlL) or edema when albumin level is not available
Complete remission
First morning urine or 24-hour urinary protein-to-creatinine ratio ≤ 200 mg/g (0.2 g/g or 20 mg/mmol or negative or trace dipstick or < 100 mg/m² per day) on ≥ 3 consecutive days
Partial remission
First morning urine or 24-hour urinary protein-to-creatinine ratio > 200 mg/g (0.2 g/g) but < 2 g/g (or > 20 and < 200 mg/mmol) and, if available, serum albumin ≥ 30 g/L (3 g/dL)
Relapse
Recurrence of nephrotic-range proteinuria in a child who had previously achieved complete remission
Assess relapse commonly by urine dipstick, defined as dipstick ≥ 3+ for 3 consecutive days
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Recognize that typical dipstick results are expressed semiquantitatively as follows, or as stated by the manufacturer:
Situation
Guidance
Negative
0 to < 15 mg/dL
Trace
15 to <30 mg/dL
1+
30 to < 100 mg/dL
2+
100 to < 300 mg/dL
3+
300 to < 1,000 mg/dL
4+
≥ 1,000 mg/dL
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Revised Schwartz Equation for GFR (2009)
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Classification and risk stratification

Classification: as per KDIGO 2025 guidelines, use the following classification for nephrotic syndrome in children:
Situation
Guidance
Steroid-sensitive nephrotic syndrome
Complete remission within 4 weeks of prednisone or prednisolone at standard dose
Infrequently relapsing nephrotic syndrome
< 2 relapses in the 6 months following remission of the initial episode or < 3 relapses in any subsequent 12-month period
Frequently relapsing nephrotic syndrome
≥ 2 relapses in the first 6 months following remission of the initial episode or ≥ 3 relapses per 12 months in any subsequent 12-month period
Steroid-dependent nephrotic syndrome
2 consecutive relapses during recommended prednisone or prednisolone therapy for first presentation or relapse (either at full-dose or during tapering) or within 14 days of prednisone or prednisolone discontinuation
Steroid-resistant nephrotic syndrome
Lack of complete remission within 4 weeks of therapy with daily prednisone or prednisolone at standard dose
Confirmation period
Time period between 4 and 6 weeks from prednisone or prednisolone initiation during which response to further oral prednisone or prednisolone and/or pulses of IV methylprednisolone and renin-angiotensin system inhibitors are ascertained in patients achieving only partial remission at 4 weeks
Define a patient achieving complete remission at 6 weeks as a late responder
Define a patient not achieving complete remission at 6 weeks, although achieving partial remission at 4 weeks, as steroid-resistant nephrotic syndrome
Steroid-sensitive nephrotic syndrome late responder
A patient with new-onset nephrotic syndrome achieving complete remission during the confirmation period (between 4 and 6 weeks of prednisone or prednisolone therapy)
Calcineurin inhibitor-responsive steroid-resistant nephrotic syndrome
Partial remission with 6 months of treatment and/or complete remission with 12 months of treatment with a calcineurin inhibitor at adequate doses and/or levels
Calcineurin inhibitor-resistant steroid-resistant nephrotic syndrome
Absence of partial remission with at least 6 months of treatment with a calcineurin inhibitor at adequate doses and/or levels
Multi-drug resistant steroid-resistant nephrotic syndrome
Absence of complete remission with 12 months of treatment with 2 mechanistically distinct steroid-sparing agents at standard doses
Secondary steroid-resistant nephrotic syndrome
A patient with steroid-sensitive nephrotic syndrome at disease onset who at a subsequent relapse fails to achieve remission within 4 weeks of therapy with daily prednisone or prednisolone at standard dose
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Diagnostic investigations

Initial evaluation: as per IPNA 2023 guidelines, obtain a work-up for the diagnosis of nephrotic syndrome in all children presenting with gravity-dependent edema.
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  • Laboratory testing

  • Genetic testing

  • Diagnostic imaging

Diagnostic procedures

Kidney biopsy
As per KDIGO 2025 guidelines:
Avoid performing a kidney biopsy at the initial presentation of nephrotic syndrome in children, as prognosis is best predicted by the response to initial treatment and the relapse frequency within the first year. Reserve kidney biopsy for cases with treatment resistance or an atypical clinical course.
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Perform a kidney biopsy in children with nephrotic syndrome in the following circumstances:
age ≥ 12 years
steroid-resistant nephrotic syndrome or subsequent failure to respond to corticosteroids in steroid-sensitive nephrotic syndrome (secondary steroid-sensitive nephrotic syndrome)
a high index of suspicion for a different underlying pathology, such as macroscopic hematuria, systemic symptoms of vasculitis, or hypocomplementemia
kidney failure at onset not related to hypovolemia
decreasing kidney function in children receiving calcineurin inhibitors or prolonged exposure to calcineurin inhibitors (2-3 years)
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Medical management

Management of initial relapse, corticosteroids
As per KDIGO 2025 guidelines:
Administer oral corticosteroids for 8 weeks (4 weeks of daily corticosteroids followed by 4 weeks of alternate-day corticosteroids) or 12 weeks (6 weeks of daily corticosteroids followed by 6 weeks of alternate-day corticosteroids).
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Administer the standard dosing regimen for the initial treatment of nephrotic syndrome with daily oral prednisone or prednisolone at 60 mg/m²/day or 2 mg//kg/day (maximum 60 mg/day) for 4 weeks, followed by alternate-day prednisone or prednisolone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg) for another 4 weeks, or prednisone or prednisolone at 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day) for 6 weeks, followed by alternate-day prednisone or prednisolone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg) for another 6 weeks.
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  • Management of initial relapse (other agents)

  • Management of initial relapse (monitoring)

  • Management of subsequent relapses (corticosteroids)

  • Management of subsequent relapses (corticosteroid-sparing agents)

  • Management of subsequent relapses (upper respiratory tract infections)

  • Management of steroid-resistant nephrotic syndrome

  • Management of hypertension

  • Management of edema

  • Management of hypovolemia

  • Prevention of thrombosis

  • Prevention of infections

  • Prevention of endocrine abnormalities

  • Preservation of bone health

Nonpharmacologic interventions

Fluid and salt restrictions: as per IPNA 2023 guidelines, assess the volume status in children experiencing an acute nephrotic state.
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  • Lifestyle modifications

Specific circumstances

Patients with congenital nephrotic syndrome, initial evaluation: as per ERN ERKNet/ESPN 2021 guidelines, obtain an initial diagnostic evaluation, including medical history, clinical and biological evaluation of congenital nephrotic syndrome complications and associated non-kidney features.
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  • Patients with congenital nephrotic syndrome (kidney biopsy)

  • Patients with congenital nephrotic syndrome (setting of care)

  • Patients with congenital nephrotic syndrome (fluid management)

  • Patients with congenital nephrotic syndrome (diuretics)

  • Patients with congenital nephrotic syndrome (RAAS inhibitors)

  • Patients with congenital nephrotic syndrome (prostoglandin inhibitors)

  • Patients with congenital nephrotic syndrome (immunosuppressive therapy)

  • Patients with congenital nephrotic syndrome (nephrectomy)

  • Patients with congenital nephrotic syndrome (lifestyle modifications)

  • Patients with congenital nephrotic syndrome (prevention of thrombosis)

  • Patients with congenital nephrotic syndrome (prevention of infections)

  • Patients with congenital nephrotic syndrome (preservation of bone health)

  • Patients with congenital nephrotic syndrome (management of secondary nephrotic syndrome)

  • Patients with congenital nephrotic syndrome (management of endocrine abnormalities)

  • Patients with congenital nephrotic syndrome (management of anemia)

  • Patients with congenital nephrotic syndrome (management of kidney failure)

Preventative measures

Routine immunizations: as per IPNA 2023 guidelines, review the patient's vaccination status at disease onset and complete all inactivated vaccinations according to the schedule recommended for healthy children without delay, with particular emphasis on encapsulated bacteria (pneumococcus, meningococcus, and H. influenzae).
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Follow-up and surveillance

Indications for referral: as per IPNA 2023 guidelines, refer patients to a pediatric nephrologist in the following scenarios:
atypical features not consistent with idiopathic nephrotic syndrome
positive family history for nephrotic syndrome
congenital or infantile onset nephrotic syndrome
age at onset of nephrotic syndrome ≥ 12 years
secondary nephrotic syndrome
steroid-resistant nephrotic syndrome
steroid-sensitive nephrotic syndrome late responder
frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome
steroid-sensitive nephrotic syndrome patients with drug toxicities or complicated relapses.
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  • Transition to adult care