What is the recommended corticosteroid dosing regimen, including initial dose and taper schedule, for an adult with primary nephrotic syndrome?

Corticosteroid Dosing for Adult Nephrotic Syndrome

For adults with primary nephrotic syndrome, initiate prednisone at 1 mg/kg/day (maximum 80 mg) or 2 mg/kg on alternate days (maximum 120 mg), continue high-dose therapy for at least 4 weeks and up to 16 weeks until complete remission is achieved, then taper slowly over 6 months for a total treatment duration of 6 months. 1

Initial High-Dose Phase

Dosing Options

• Daily dosing: Prednisone 1 mg/kg/day as a single morning dose (maximum 80 mg/day) 1
• Alternate-day dosing: Prednisone 2 mg/kg on alternate days (maximum 120 mg on alternate days) 1
• Both regimens are equally effective, though daily dosing is used most commonly in clinical practice 1

Duration of High-Dose Therapy

• Minimum duration: Continue high-dose therapy for at least 4 weeks, even if remission occurs earlier 1
• Maximum duration: Do not exceed 16 weeks of high-dose therapy 1
• Response assessment: Most patients who will respond show some proteinuria reduction within 4-8 weeks 1
• Early discontinuation: If no response by 8-12 weeks and significant steroid toxicity develops, consider switching to calcineurin inhibitors rather than continuing high-dose steroids 1

Tapering Phase

When to Begin Tapering

• For rapid responders: Begin tapering 2 weeks after achieving complete remission 1
• For slower responders: If partial remission achieved at 8-12 weeks, continue high-dose therapy until 16 weeks to assess for further improvement, then begin taper 1

Taper Schedule

• Reduce prednisone by 5 mg every 1-2 weeks 1
• Total treatment duration should be 6 months (high-dose phase plus taper) 1
• The slow taper is critical—studies show relapse rates of 81% with 2-month courses versus 59% with 6-month courses 2

Disease-Specific Considerations

Minimal Change Disease (MCD)

• Response rate: 76% of adults achieve remission by 8 weeks (compared to >95% in children by 4 weeks) 3, 4
• Response time: May take up to 16 weeks for complete remission in adults 4, 5
• Relapse risk: 34% of adults experience relapse, with higher rates in patients under 30 years old 4

Focal Segmental Glomerulosclerosis (FSGS)

• Lower response rate: Only 20-30% of FSGS patients respond to steroids alone 6
• Same dosing regimen: Use identical prednisone dosing as for MCD 1
• Earlier switch to alternatives: If no response by 8-12 weeks, strongly consider switching to calcineurin inhibitors rather than continuing steroids to 16 weeks 1

Alternative First-Line Therapy

When to Use Calcineurin Inhibitors Instead

Consider CNIs as initial therapy for patients with: 1

• Uncontrolled diabetes mellitus
• Severe psychiatric conditions
• Severe osteoporosis
• Previous severe steroid toxicity

CNI Dosing

• Cyclosporine: 3-5 mg/kg/day in 2 divided doses, target trough 100-175 ng/mL 1
• Tacrolimus: 0.05-0.1 mg/kg/day in 2 divided doses, target trough 5-10 ng/mL 1
• Duration: Continue for at least 4-6 months before declaring treatment failure 1
• Combine with low-dose prednisone (0.15 mg/kg/day) when using CNIs 1, 6

Monitoring and Response Definitions

Complete Remission

• Proteinuria <200 mg/g (<20 mg/mmol) or trace/negative on dipstick for 3 consecutive days 1, 3
• This is the target outcome that predicts excellent long-term kidney survival 1

Partial Remission

• ≥50% reduction in proteinuria from baseline 1
• If only partial remission achieved by 16 weeks, still proceed with taper but consider adding CNI 1

Steroid Resistance

• Defined as no remission after 8-16 weeks of adequate corticosteroid therapy 3
• Switch to CNI-based regimen rather than prolonging steroids 1, 3

Critical Pitfalls to Avoid

Insufficient Treatment Duration

• Do not stop steroids before 4 weeks even if remission occurs earlier—this increases relapse risk 1, 2
• Do not use short 2-month courses—the full 6-month protocol (including taper) significantly reduces relapses 2

Excessive Treatment Duration

• Do not continue high-dose steroids beyond 16 weeks if no response—toxicity outweighs potential benefit 1
• The risk of severe complications (infections, avascular necrosis, diabetes, psychiatric effects) increases substantially with prolonged high-dose therapy 1

Premature Dose Escalation

• Do not exceed 80 mg/day (or 120 mg alternate-day)—higher doses do not improve response rates but dramatically increase toxicity 1

Inadequate Monitoring

• Monitor proteinuria weekly during high-dose phase using urine protein-to-creatinine ratio or 24-hour collection 3
• Check serum creatinine, potassium, glucose, and blood pressure at least every 2-4 weeks 2
• Watch for early signs of steroid toxicity to allow timely switch to alternative agents 1

Management of Relapses

Infrequent Relapses

• Retreat with same initial regimen: prednisone 1 mg/kg/day until remission (minimum 3 days proteinuria-free) 1, 7
• Then switch to 40 mg/m² (or 1.5 mg/kg) on alternate days for at least 4 weeks 1, 2

Frequent Relapses or Steroid Dependence

• Do not repeatedly use high-dose steroids—cumulative toxicity becomes prohibitive 1, 7
• Switch to steroid-sparing agents: rituximab, cyclophosphamide (2-2.5 mg/kg/day for 8 weeks), or CNIs 1, 7, 5
• If continuing steroids, use lowest dose to maintain remission on alternate-day schedule 1, 2