When can a trial of steroids (corticosteroids) be considered for nephrotic syndrome?

When to Give a Trial of Steroids for Nephrotic Syndrome

Steroids should be initiated immediately as first-line therapy in children and adults presenting with nephrotic syndrome when minimal change disease or focal segmental glomerulosclerosis is suspected, starting at 1 mg/kg/day (maximum 80 mg) or 60 mg/m²/day for at least 4 weeks before determining steroid responsiveness. 1, 2

Immediate Initiation Without Biopsy

In children presenting with nephrotic syndrome:

• Start prednisone 60 mg/m²/day (maximum 80 mg/day) immediately without waiting for kidney biopsy 1, 3
• Continue daily dosing for 4 weeks, then switch to 40 mg/m²/day on alternate days for several weeks 3
• Response typically occurs within 11 days in children (may take up to 16 weeks in adults) 3
• Critical pitfall: Only perform kidney biopsy if no response occurs after 4 weeks of daily prednisone at 60 mg/m²/day—this defines steroid resistance 2

In adults presenting with nephrotic syndrome:

• Adults require longer trial periods: up to 8 weeks of daily prednisone before determining steroid resistance 2
• If no partial remission by 8 weeks or unacceptable steroid side effects develop, proceed to kidney biopsy and consider alternative agents 2

Disease-Specific Steroid Indications

Minimal Change Disease

• Prednisone 1 mg/kg/day (max 80 mg) or 2 mg/kg alternate-day (max 120 mg) is standard initial treatment, even with reduced kidney function 1
• Induces remission in 93% of children and 81% of adults 3
• Can discontinue abruptly at end of treatment course without tapering 3

Focal Segmental Glomerulosclerosis (FSGS)

• Children: Initiate steroids first; only after 4 weeks of non-response at 60 mg/m²/day should biopsy be performed 2
• If biopsy confirms FSGS, continue prednisone at 60 mg/m²/day and add cyclosporine 100-150 mg/m²/day in divided doses 2
• Adults: Those not achieving partial remission by 8 weeks of daily prednisone should transition to cyclosporine 2-4 mg/kg/day with low-dose alternate-day prednisone 2

Membranous Nephropathy

• Do NOT use steroids as monotherapy—meta-analysis shows no effect on renal survival or remission 2
• Exception: Japanese populations may benefit from 4-week corticosteroid course (racial variation in therapeutic responsiveness) 2
• For moderate-to-high risk patients (proteinuria >4 g/day), combine glucocorticoids with cyclophosphamide or rituximab 1

Membranoproliferative Glomerulonephritis (MPGN)

• In children with MPGN and nephrotic syndrome: trial of alternate-day prednisone 40 mg/m² for 6-12 months (possibly longer if clear clinical response) 2
• Renal survival improved to 61% at 130 months versus 12% with placebo 2, 1
• In adults: only use if accompanied by progressive decline in kidney function; combine with cyclophosphamide or MMF for initial therapy limited to <6 months 2

Absolute Contraindications to Steroid Trials

Do NOT initiate steroids in the following scenarios:

• Advanced CKD with severe tubulointerstitial fibrosis, small kidney size, or chronic inactive disease—immunosuppression causes only harm 2, 1
• GFR <30 mL/min/1.73 m² unless crescentic glomerulonephritis with rapidly deteriorating kidney function 4
• IgA-dominant postinfectious glomerulonephritis (must distinguish from IgA nephropathy to avoid inappropriate steroid use) 1
• Diabetic kidney disease without active glomerular inflammation—steroids worsen glycemic control without renal benefit 1

Pre-Treatment Requirements

Before initiating prednisone, assess:

• Current blood pressure control and eGFR 1
• Ensure blood pressure is at target (<130/80 mm Hg); intensify antihypertensive therapy if necessary before starting steroids 1
• Rule out active infections (steroids suppress immune response and increase infection risk) 5
• Screen for glucose intolerance, obesity, poorly controlled hypertension (relative contraindications requiring careful risk-benefit assessment) 2

Monitoring During Steroid Trial

Essential monitoring parameters:

• Urinalysis for proteinuria response (target: first of 3 consecutive days without proteinuria) 6
• Serum creatinine and GFR regularly 4
• Blood pressure (hypertension indicates more severe renal involvement) 7
• Potassium levels, especially if on ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists 1
• In children: growth velocity, weight, height, intraocular pressure, and clinical evaluation for infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis 5

Defining Treatment Response and Next Steps

Response criteria:

• Complete remission: Proteinuria <0.3 g/day or urine protein/creatinine ratio <0.3 mg/mg
• Partial remission: ≥50% reduction in proteinuria with absolute value <3.5 g/day
• No response: <50% reduction in proteinuria after adequate trial duration

If no response after adequate trial:

• Children: 4 weeks at 60 mg/m²/day defines steroid resistance; proceed to biopsy and consider cyclosporine 2
• Adults: 8 weeks of daily prednisone; if no partial remission, transition to cyclosporine or other second-line agents 2
• FSGS: Minimum 50% reduction in baseline proteinuria required by 6 months; otherwise add or switch to alternative agents 2

Relapse Management

For steroid-sensitive nephrotic syndrome relapses:

• Traditional approach: prednisone 2 mg/kg/day or 60 mg/m²/day until remission 6
• Lower-dose alternative: 1-1.5 mg/kg/day achieves remission with significantly lower cumulative dose and similar efficacy (response time 9-10 days vs 7 days with standard dose) 6
• After remission, continue alternate-day dosing for 4 weeks 3
• In adults: alternate-day prednisone for 1 year after presenting attack decreases relapse risk 3

Critical Pitfalls to Avoid

• Do NOT use corticosteroids prophylactically in Henoch-Schönlein purpura (HSP) at disease onset to prevent nephritis—Level 1B evidence shows no benefit 2, 7
• Do NOT delay biopsy indefinitely in adults with atypical presentations or risk factors for secondary causes of nephrotic syndrome
• Do NOT use NSAIDs for symptom control in nephrotic syndrome patients—they can cause acute kidney injury; use acetaminophen instead 7
• Do NOT continue steroids beyond 6 months in MPGN without clear clinical response—taper and discontinue if no significant proteinuria reduction 2