What is the recommended treatment and management for fibrillary glomerulonephritis in a middle‑aged adult presenting with nephrotic‑range proteinuria, microscopic hematuria, and progressive renal dysfunction?

Fibrillary Glomerulonephritis: Treatment and Management

Primary Treatment Recommendation

For a middle-aged adult with fibrillary glomerulonephritis presenting with nephrotic-range proteinuria, microscopic hematuria, and progressive renal dysfunction, initiate rituximab-based immunosuppression combined with aggressive nephroprotective measures, as this represents the most promising therapeutic approach based on available evidence. 1, 2

Initial Conservative Management (Start Immediately)

• Begin maximally tolerated ACE inhibitor or ARB therapy immediately to reduce proteinuria and slow disease progression 3, 4
• Target blood pressure <120 mmHg systolic using standardized office measurements 4
• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) to enhance antiproteinuric effects 4
• Monitor serum creatinine and potassium 1-2 weeks after initiating RAS blockade, accepting up to 30% creatinine elevation if it stabilizes 4

Immunosuppressive Therapy Selection

Rituximab-based regimens should be prioritized as first-line immunosuppression for fibrillary GN. 1, 2

Evidence Supporting Rituximab:

• In the largest French case series, 5 of 7 patients treated with rituximab achieved renal response (>50% decrease in proteinuria with <15% decline in eGFR), compared to only 1 of 3 patients treated with cyclophosphamide 1
• A more recent series showed 4 of 7 patients (57%) treated with rituximab-based regimens achieved clinical response after median 30-month follow-up 2
• Patients who responded to rituximab typically had mesangial or membranous light microscopic patterns and better preserved renal function (median eGFR 76 mL/min/1.73 m²) at treatment initiation 1

Alternative Immunosuppressive Options:

• Corticosteroid monotherapy (prednisone 1 mg/kg/day with individualized taper) may be considered in patients with early diagnosis, preserved renal function, and nephrotic syndrome, as three patients achieved complete or near-complete remission with this approach 5
• Cyclophosphamide plus corticosteroids can be used as second-line therapy if rituximab fails or is contraindicated, though response rates appear lower 1, 2

Patient Selection for Immunosuppression

Immunosuppressive therapy is most likely to benefit patients with:

• Preserved renal function (eGFR >60 mL/min/1.73 m²) at presentation 1, 5
• Mesangial or membranous light microscopic patterns (rather than membranoproliferative or sclerosing patterns) 1
• Early disease without extensive tubulointerstitial fibrosis on biopsy 6

Avoid immunosuppression in patients with:

• Advanced CKD (eGFR <25-30 mL/min/1.73 m²) 6
• Severe tubulointerstitial fibrosis or small kidney size suggesting chronic inactive disease 6

Critical Timing Considerations

Early initiation of immunosuppression appears crucial for favorable outcomes in fibrillary GN. 5

• Unlike membranous nephropathy where 6 months of conservative therapy is recommended before immunosuppression 6, 7, fibrillary GN has a more aggressive natural history with 50% progressing to end-stage renal disease within 2-4 years 1, 8, 9
• In the French series, 12 of 14 patients (86%) who received only conservative therapy progressed to advanced CKD, with 10 reaching end-stage renal disease 1
• The three patients who responded to corticosteroids all had normal renal function at diagnosis and were treated early 5

Monitoring Strategy

• Recheck proteinuria (UPCR), serum creatinine, and eGFR every 4-6 weeks initially to assess treatment response 3
• Define renal response as >50% decrease in 24-hour proteinuria with <15% decline in eGFR 1
• Evidence of proteinuria improvement should be apparent by 3 months, with at least 50% reduction by 6 months 4
• Monitor for rituximab-related complications including infusion reactions and infections 2

Additional Supportive Measures

• Consider prophylactic anticoagulation with warfarin if serum albumin <2.5 g/dL with additional thrombosis risk factors, given nephrotic syndrome 7
• Manage edema with diuretics as needed 7
• Screen for associated conditions including autoimmune diseases, hepatitis C, and malignancies, though these associations remain debated 8, 9

Critical Pitfalls to Avoid

• Do not delay immunosuppression for 6 months as recommended for membranous nephropathy—fibrillary GN has a much more aggressive natural history requiring earlier intervention 1, 5
• Do not use high-dose corticosteroids alone in patients with already impaired renal function—rituximab appears more effective in this population 1
• Do not initiate immunosuppression in patients with advanced CKD or extensive fibrosis—these patients are unlikely to benefit and face significant treatment-related risks 6, 1

Prognosis and Transplantation

• Overall renal prognosis remains guarded, with 50% progressing to end-stage renal disease within 2-4 years despite treatment 8, 9
• Kidney transplantation is a viable option for end-stage renal disease, though recurrence in the transplanted kidney occurs in a significant proportion of patients 9