What is the treatment approach for nephritis based on microscopic and Immunofluorescence (IF) findings?

Treatment Approach for Nephritis Based on Microscopic and Immunofluorescence (IF) Findings

The treatment of nephritis should be guided by the specific histopathological classification determined by renal biopsy, with immunosuppressive therapy regimens tailored to the ISN/RPS class identified through microscopic and immunofluorescence findings.

Importance of Renal Biopsy

Renal biopsy is essential for patients with clinical evidence of active nephritis to:

• Classify glomerular disease according to ISN/RPS classification
• Evaluate disease activity and chronicity
• Identify tubular and vascular changes
• Rule out alternative causes of renal disease 1

Treatment Based on Histological Classification

Class I (Minimal Mesangial Lupus Nephritis)

• Characterized by minimal mesangial immune deposits on IF with normal light microscopy
• No immunosuppressive treatment required 1, 2
• Supportive care only

Class II (Mesangial Proliferative Lupus Nephritis)

• Characterized by mesangial hypercellularity/matrix expansion on light microscopy with immune deposits confined to mesangium on IF
• No immunosuppressive treatment required 1, 2
• Hydroxychloroquine and supportive care recommended

Class III (Focal Lupus Nephritis)

• Characterized by subendothelial immune deposits and proliferative changes in <50% of glomeruli
• Requires aggressive immunosuppressive therapy:
  • Initial treatment: Glucocorticoids plus either mycophenolate mofetil (MMF) or cyclophosphamide 1, 2
  • Recommended regimen: Three consecutive pulses of IV methylprednisolone 500-750mg, followed by oral prednisone 0.5mg/kg/day for 4 weeks, tapering to ≤10mg/day by 4-6 months 2
  • MMF target dose: 3g/day for 6 months OR
  • Low-dose IV cyclophosphamide: total dose 3g over 3 months 2

Class IV (Diffuse Lupus Nephritis)

• Characterized by subendothelial deposits and proliferative glomerular changes involving ≥50% of glomeruli
• Most severe form requiring aggressive immunosuppression:
  • Same regimen as Class III 1, 2
  • Higher doses of cyclophosphamide (0.75-1g/m² monthly for 6 months) may be considered in severe cases 2

Class V (Membranous Lupus Nephritis)

• Characterized by subepithelial immune deposits and membranous thickening of glomerular capillaries
• Treatment approach:
  • Pure Class V with nephrotic-range proteinuria: MMF with prednisone 2
  • When combined with Class III or IV: Treat as Class III or IV 1, 2
  • Calcineurin inhibitors can be considered in pure Class V nephritis 1

Class VI (Advanced Sclerosing Lupus Nephritis)

• Characterized by sclerosis of ≥90% of glomeruli
• Preparation for renal replacement therapy rather than immunosuppression 2

Maintenance Therapy

After successful induction therapy:

• MMF (2g/day) or azathioprine (2mg/kg/day) for at least 3 years
• Combined with low-dose prednisone (5-7.5mg/day) 1, 2
• Patients who responded to initial treatment with MMF should remain on MMF unless pregnancy is contemplated (switch to azathioprine at least 3 months prior to conception) 1

Refractory Disease Management

For patients who fail treatment with either MMF or cyclophosphamide:

• Switch from MMF to cyclophosphamide or vice versa
• Consider rituximab 1

Adjunctive Treatments

1. Hydroxychloroquine for all lupus nephritis patients (unless contraindicated) to reduce flares and limit renal damage 1, 2
2. ACE inhibitors or ARBs for patients with proteinuria or hypertension 1, 2
3. Blood pressure control with target ≤130/80 mmHg 1, 2
4. Statins for persistent dyslipidemia (target LDL <100mg/dl) 1, 2
5. Acetylsalicylic acid in patients with anti-phospholipid antibodies 1, 2

Monitoring and Treatment Goals

• Regular monitoring of renal function, proteinuria, urinary sediment, serum C3/C4, and anti-dsDNA antibody levels 1
• Treatment goals:
  • Complete renal response: proteinuria <500mg/24h with normal/near-normal renal function
  • Partial response: ≥50% reduction in proteinuria to subnephrotic levels with normal/near-normal renal function 2
• Partial response should be achieved by 6 months and complete response by 12 months 2
• Consider repeat renal biopsy in cases of treatment failure, relapse, or worsening of GFR 1

Cautions and Pitfalls

1. Delaying treatment can lead to irreversible kidney damage and progression to end-stage renal disease
2. Inadequate immunosuppression in Class III and IV nephritis can result in poor outcomes 3
3. Overtreatment of Class I and II nephritis exposes patients to unnecessary immunosuppression risks
4. Failure to provide adjunctive treatments (hydroxychloroquine, ACE inhibitors/ARBs) reduces treatment efficacy
5. Inadequate monitoring may miss early signs of treatment failure or disease relapse

By following this treatment approach based on microscopic and IF findings, clinicians can optimize outcomes and prevent progression to end-stage renal disease in patients with nephritis.