What are the indications and dosing regimens for Intravenous Immunoglobulin (IVIG) in nephrology practice?

Intravenous Immunoglobulin (IVIG) in Nephrology Practice: Indications and Dosing Regimens

IVIG therapy in nephrology should be reserved for specific conditions including antibody-mediated rejection in kidney transplantation, desensitization protocols, ANCA-associated vasculitis with rapidly progressive glomerulonephritis, and as adjunctive therapy for certain viral infections in immunocompromised transplant recipients.

Primary Indications for IVIG in Nephrology

1. Kidney Transplantation Applications

• Antibody-mediated rejection: IVIG is used as part of treatment protocols 1
• Desensitization protocols: For highly sensitized transplant candidates to reduce anti-HLA antibodies 1
• ABO-incompatible transplantation: To reduce antibody titers before transplantation 1

2. Glomerular Diseases

• ANCA-associated vasculitis with rapidly progressive glomerulonephritis:

  • Dosing: 400 mg/kg/day for 5 consecutive days 2
  • Can be administered before or alongside conventional immunosuppressive therapy
  • Particularly beneficial in elderly patients with MPO-ANCA related disease 2

• Treatment-resistant chronic glomerulonephritis with severe nephrotic syndrome:

  • Dosing: 85 mg/kg every other day for 3 doses 3
  • May be repeated monthly in responsive patients 3

3. Viral Infections in Transplant Recipients

• CMV pneumonitis: Adjunctive IVIG can be administered every other day for 3-5 doses 4
• Prevention of CMV in high-risk transplant patients: Often used alongside antiviral agents 4
• Hepatitis B prophylaxis: Specific hepatitis B hyperimmune globulin (HBIG) is preferred over standard IVIG 1

Standard Dosing Regimens

The standard IVIG dose across most indications is 2 g/kg total dose, typically administered over 2-5 days 5. However, specific nephrology indications have tailored protocols:

1. ANCA-associated vasculitis: 400 mg/kg/day for 5 days (total 2 g/kg) 2
2. Chronic glomerulonephritis: 85 mg/kg every other day for 3 doses 3
3. Transplant desensitization: Protocols vary by center but typically involve 2 g/kg divided over 2-4 days 1
4. CMV prophylaxis/treatment: Standard IVIG or CMV-specific immunoglobulin, dosing varies by protocol 4

Monitoring and Adverse Effects

Required Monitoring

• Renal function: Check baseline creatinine and monitor during therapy 6
  • Incidence of renal impairment: up to 6.7% of patients receiving IVIG 6
  • Risk of irreversible renal damage: approximately 1.7% 6
• IgA levels: Check before first administration to avoid anaphylaxis in IgA-deficient patients 4
• Vital signs: Monitor during infusion for reactions 5

Major Adverse Effects

• Acute kidney injury: More common with sucrose-containing IVIG preparations 7
  • Mechanism: osmotic nephrosis causing vacuolization and swelling of proximal tubules 7
  • Risk factors: pre-existing renal disease, volume depletion, advanced age 7
• Thrombotic events: Particularly in patients with cardiovascular risk factors 4
• Hemolysis: Especially after high-dose infusions 4

Risk Mitigation Strategies

1. For patients with renal impairment:

   • Use lower doses or slower infusion rates 5
   • Consider non-sucrose containing IVIG preparations 7
   • Ensure adequate hydration before and during infusion

2. For patients with IgA deficiency:

   • Screen for anti-IgA antibodies 4
   • Consider subcutaneous immunoglobulin as an alternative in high-risk patients 4

3. For all patients:

   • Monitor renal function before, during, and after IVIG therapy 6
   • Adjust dosing based on ideal body weight in obese patients 5

Evidence Quality and Limitations

Most evidence for IVIG use in nephrology comes from small case series and observational studies rather than large randomized controlled trials. The strongest evidence exists for:

1. Antibody-mediated rejection in transplantation
2. ANCA-associated vasculitis with rapidly progressive glomerulonephritis
3. Desensitization protocols

For other nephrology indications, IVIG should be considered when conventional therapies have failed or are contraindicated.