What is the recommended steroid tapering protocol for an adult with newly diagnosed nephrotic syndrome who is started on oral prednisone (or an equivalent glucocorticoid such as prednisolone)?

Steroid Tapering Protocol for Adult Nephrotic Syndrome

Recommended Tapering Regimen

For adults with newly diagnosed nephrotic syndrome, start prednisone at 1 mg/kg/day (maximum 80 mg/day) for 4-8 weeks until remission, then taper to 40 mg/m² on alternate days for 2-5 months, with the total treatment duration extending up to 6 months to minimize relapse risk. 1

Initial Daily Phase (4-8 Weeks)

• Begin oral prednisone at 1 mg/kg/day as a single morning dose 2
• Continue daily dosing for a minimum of 4 weeks, but extend up to 8 weeks if remission has not yet occurred 2
• Adults typically respond more slowly than children, with remission occurring in an average of 16 weeks (compared to 11 days in children) 3
• Approximately 81% of adults will achieve remission with this regimen 3
• Define remission as: urine protein trace/negative on dipstick for 3 consecutive days or protein-to-creatinine ratio <200 mg/g 4

Alternate-Day Phase (2-5 Months)

• Once remission is achieved, switch to 40 mg/m² on alternate days 1, 3
• Continue alternate-day dosing for 2-5 months 1
• The total treatment duration from initiation should be at least 12 weeks, ideally extending to 6 months 1
• Longer courses (6 months total) reduce relapse rates from 81% to 59% compared to shorter 2-month courses 1

Gradual Taper to Discontinuation

• After completing the alternate-day phase, taper by 10 mg/m² per week until reaching 5 mg on alternate days 1
• The medication can then be discontinued abruptly at the end of the treatment course 3
• Total treatment duration should be up to 6 months after achieving remission to optimize long-term outcomes 1

Critical Monitoring During Taper

• Check daily urine dipstick throughout the taper phase 1
• Monitor blood pressure and potassium levels regularly 1
• Watch for signs of relapse: ≥2+ proteinuria for 3 consecutive days or ≥2+ proteinuria with edema 1
• Monitor serum creatinine and GFR 1

Management of Relapses

For Infrequent Relapses

• Give prednisone 60 mg/m²/day until remission (typically 3 consecutive days of trace/negative proteinuria) 1
• Then switch to 40 mg/m² on alternate days for 4 weeks 1

For Frequent Relapses or Steroid-Dependent Disease

• Give prednisone 60 mg/m²/day until remission 1
• Switch to 40 mg/m² on alternate days for 1 week 1
• Then taper by 10 mg/m² per week to complete a total of 4 weeks 1

When to Consider Steroid-Sparing Agents

• If steroid resistance develops (no remission after 8-16 weeks of appropriate therapy), do not continue tapering steroids 1
• Switch to calcineurin inhibitors: cyclosporine 3-5 mg/kg/day or tacrolimus 0.05-0.1 mg/kg/day with low-dose corticosteroids 1
• For steroid-dependent disease or significant steroid toxicity, consider cyclophosphamide, cyclosporine, or levamisole as alternatives 1
• Tacrolimus may achieve faster remission than cyclophosphamide in steroid-dependent cases (mean time to remission significantly shorter) 5

Important Clinical Pitfalls to Avoid

• Do not use shorter tapering courses: The evidence clearly shows that 2-month courses result in 81% relapse rates versus 59% with 6-month courses 1
• Do not taper too quickly: Slow tapering over the full 6-month period is essential even though it means higher cumulative steroid exposure initially 1
• Do not continue steroids beyond 8-16 weeks in non-responders: This indicates steroid resistance and requires alternative therapy 1
• Adults require longer treatment than children: Response may take up to 16 weeks in adults versus days in children 3
• Prednisone does not require dose adjustment even in advanced CKD (GFR <50 mL/min) 1

Special Considerations for Adults

• In adults with minimal change disease, alternate-day prednisone for 1 year after the presenting attack decreases the risk of relapse 3
• Younger adults (<30 years) have higher relapse rates than older adults (≥30 years) 2
• Complete remission rates in adults are approximately 94% with appropriate treatment duration 2
• Relapse occurs in approximately 34% of adults, with 63-75% remaining in remission at 1 year 2