What is the management of immune complex mediated glomerulonephritis?

Management of Immune Complex Mediated Glomerulonephritis

The management of immune complex mediated glomerulonephritis (ICGN) requires identification of underlying causes and appropriate immunosuppressive therapy based on disease severity, with rituximab recommended as first-line immunosuppressive treatment in patients with histologically active disease who do not respond to antiviral therapy. 1

Diagnostic Evaluation

• Evaluate all patients with ICGN for underlying diseases including infections (HBV, HCV), autoimmune disorders, and malignancies before initiating treatment 1
• Perform comprehensive complement analysis to assist with diagnosis, even in the absence of hypocomplementemia 1
• Screen for paraproteins with serum and urine electrophoresis, immunofixation, and free light chain analysis when monoclonal immunoglobulin deposits are found 1
• Evaluate patients ≥50 years with C3 glomerulopathy for the presence of monoclonal proteins 1

Treatment Approach Based on Disease Severity

For Indolent ICGN (Proteinuria <3.5 g/day, normal eGFR)

• Provide supportive therapy with RAS inhibition alone 1
• Monitor regularly for worsening proteinuria or declining kidney function 1

For ICGN with Nephrotic Syndrome but Stable Kidney Function

• Treat with direct-acting antivirals (DAAs) prior to other treatments if HCV-associated 1
• Use immunosuppressive therapy only after excluding secondary causes 1

For Rapidly Progressive Glomerulonephritis or Cryoglobulinemic Flare

• Initiate combined therapy with both DAAs and immunosuppressive agents with or without plasma exchange for HCV-associated cases 1
• For non-HCV related cases with severe presentation, use cyclophosphamide and corticosteroids plus plasmapheresis 1
• Consider rituximab as first-line immunosuppressive treatment for patients with histologically active disease who don't respond to antiviral therapy 1

Specific Treatment Regimens

For HCV-Associated ICGN

• First-line: DAAs without dose adjustment (safe and effective across all CKD stages) 1
• For cryoglobulinemic flare or rapidly progressive disease: DAAs plus immunosuppression with or without plasma exchange 1
• For persistent disease despite DAA therapy: rituximab as first-line immunosuppressive agent 1

For ANCA-Associated Vasculitis with ICGN

• Induction therapy: Cyclophosphamide or rituximab combined with corticosteroids 2
• Consider combination of two IV pulses of cyclophosphamide with rituximab for severe GN 2
• Maintenance therapy: Rituximab or azathioprine plus low-dose corticosteroids for at least 18 months 2

For Anti-GBM Disease

• Initiate immunosuppression with cyclophosphamide, corticosteroids, and plasmapheresis in all patients except those who are dialysis-dependent at presentation with 100% crescents and no pulmonary hemorrhage 1
• Consider aggressive therapy even in young patients with advanced disease who might benefit from marginal preservation of renal function 1

Supportive Care

• Control blood pressure using ACE inhibitors or ARBs at maximum tolerated doses, targeting systolic BP <120 mmHg 2
• Manage edema with sodium restriction and diuretics as first-line agents 2
• Monitor for treatment-related complications and implement appropriate prophylaxis 2

Monitoring and Follow-up

• Regularly evaluate proteinuria and watch for ≥40% decrease in GFR from baseline over 2-3 years as surrogate outcomes for renal failure 2
• Screen for infections before initiating significant immunosuppression 2
• Monitor drug levels when using agents requiring therapeutic drug monitoring 2

Special Considerations

• Access to plasmapheresis may be limited in some healthcare systems; factor this into the urgency of diagnostic workup 1
• Cost considerations may influence treatment choices, particularly regarding rituximab, MMF, and plasmapheresis 1
• Consider mycophenolic acid as a cost-effective substitute for MMF in healthcare systems where coverage differs 1
• Evaluate fertility preservation options before initiating cyclophosphamide therapy 2