Nephrotic Syndrome (NS)

Note: for patients ≥18 years of age, different definitions may be used.

Nephrotic syndrome

• Heavy (nephrotic range) proteinuria

• Hypoalbuminemia (serum albumin <3.0 g/dL or <30 g/L)

• Edema

  • Often present, especially at disease onset, but not required for diagnosis unless albumin level is not known

• Hyperlipidemia (total cholesterol ≥200 mg/dL)

  • Almost always present and often severe (>350 mg/dL or >9.06 mmol/L), but not required for diagnosis

Nephrotic range proteinuria

• First morning urine protein/creatinine ratio (UPCR, PCR, UPC) ≥2.0 g/g (or ≥200 mg/mmol)

• First morning urine protein ≥300 mg/dL

• First morning urine dipstick with ≥3+ protein

  • UPCR is preferred over dipstick for establishing diagnosis

• 24-hour urine ≥40 mg/m²/hour

Remission

• Complete remission: negative/trace first morning dipstick for ≥3 consecutive days

  • Alternatively, first morning UPCR ≤0.2 g/g (or ≤20 mg/mmol) Cr for ≥3 consecutive days

    • Sequential UPCR is rarely performed in the outpatient setting

• Partial remission: sub-nephrotic range proteinuria (UPCR ≥0.2 but <2.0 g/g) and serum albumin ≥3.0 g/dL (30 g/L)

Relapse

• Recurrence of nephrotic range proteinuria for ≥3 consecutive days

• Typically detected by home urine dipstick

Steroid sensitive nephrotic syndrome (SSNS)

• Complete remission within 4 weeks of prednisone or prednisolone at a standard dose

  • Recommend avoiding use of "steroid responsive NS" as this can be confused with steroid resistant NS when abbreviated to SRNS

• SSNS can be subclassified in terms of frequency of relapse:

↪ Frequently relapsing nephrotic syndrome (FRNS)

• ≥ 2 relapses within 6 months of disease onset or ≥4 relapses in any subsequent 12 month period

↪ Infrequently relapsing nephrotic syndrome (IRNS, IFRNS, iFRNS)

• Encompassess patients who do not meet criteria for frequently relapsing nephrotic syndrome:

  • No more than 1 relapse within 6 months of disease onset

  • No more than 3 relapses in any subsequent 12 month period

↪ Steroid dependent nephrotic syndrome (SDNS)

• Two consecutive relapses during therapy with prednisone or prednisolone (either at full daily dose or during tapering) or within 15 days of stopping steroids

  • In other words, patients with SDNS are unable to come off steroids for >2 weeks without relapsing

Steroid resistant nephrotic syndrome (SRNS)

• Lack of complete remission after 4 weeks of therapy with daily prednisone or prednisolone at standard dose

↪ Late responder

• Achieved complete remission after 4 weeks but before 6 weeks of daily steroid therapy

↪ Calcineurin inhibitor (CNI) responsive SRNS

• Partial remission is achieved within 6 months of treatment and/or complete remission is achieved within 12 months of treatment with a CNI at adequate doses and/or levels

↪ Calcineurin inhibitor (CNI) resistant SRNS

• Partial remission is not achieved after 6 months of treatment with a CNI at adequate doses and/or levels

↪ Multidrug resistant SRNS

• Absence of complete remission after 12 months of treatment with two steroid sparing agents

  • The two steroid sparing agents must have distinct mechanisms and be administered at standard doses

↪ Secondary SRNS

• When a patient with SSNS at disease onset has a subsequent relapse in which they are a late responder