What is the definition of frequently relapsing nephrotic syndrome in patients with a history of kidney disease?

Definition of Frequently Relapsing Nephrotic Syndrome

Frequently relapsing nephrotic syndrome (FRNS) is defined as 2 or more relapses within the first 6 months of diagnosis OR 4 or more relapses within any 12-month period. 1

Detailed Diagnostic Criteria

Temporal Patterns for FRNS Classification

In pediatric patients:

• 2 or more relapses within 6 months of initial diagnosis, OR 1
• 4 or more relapses within any 12-month period 1

In adult patients:

• 2 or more relapses within 6 months, OR 1
• The same temporal criteria apply as in pediatric populations 1

What Constitutes a "Relapse"

Pediatric definition:

• Urine protein 3+ on dipstick (Albu-stix) OR proteinuria >40 mg/m²/h occurring on 3 consecutive days within 1 week 1
• Must occur after complete remission has been maintained for >1 month 1

Adult definition:

• Proteinuria >3.5 g/day occurring after complete remission has been obtained for >1 month 1

Clinical Significance and Implications

Disease Burden

• Children with FRNS (≥4 relapses in 12 months) will have significant cumulative exposure to high-dose corticosteroids throughout their disease course 1
• The majority of these children will develop at least 1 severe steroid side effect, including growth failure, obesity, hypertension, diabetes, osteoporosis, behavioral concerns, or cataracts 1

Treatment Threshold

• Glucocorticoid-sparing agents should be offered to children with FRNS to reduce steroid toxicity 1
• Options include cyclophosphamide, calcineurin inhibitors (CNIs), levamisole, mycophenolate, or rituximab 1

Important Distinctions from Related Entities

FRNS vs. Steroid-Dependent Nephrotic Syndrome (SDNS)

SDNS is defined as:

• 2 or more relapses during steroid taper, OR 1
• 1 relapse within 14 days of steroid cessation 1

Key difference: SDNS relapses occur specifically in relation to steroid dose reduction or discontinuation, while FRNS is defined purely by relapse frequency regardless of steroid timing 1

FRNS vs. Steroid-Resistant Nephrotic Syndrome (SRNS)

SRNS is defined as:

• No remission achieved after 8 weeks of corticosteroid treatment in children 1
• Persistence of proteinuria despite prednisone 1 mg/kg/day for >4 months in adults 1

Common Pitfalls to Avoid

• Do not confuse early relapse timing with FRNS diagnosis: A single relapse within 30 days of steroid discontinuation predicts high risk of SDNS/FRNS development (96% incidence within 6 months), but does not itself define FRNS 2
• Count relapses accurately: The definition requires counting actual relapse episodes, not just proteinuria measurements 1
• Distinguish from late-onset steroid resistance: If remission is not achieved by 6 weeks of treatment, consider SRNS rather than FRNS 1