Is IVIg (Intravenous Immunoglobulin) used in the treatment of renal transplant rejection?

Use of IVIg in Renal Transplant Rejection

IVIg is an effective component of combination therapy for antibody-mediated rejection in renal transplantation, typically administered at doses of 1-2 g/kg in divided doses alongside plasmapheresis and other immunomodulatory agents. 1

Mechanism and Rationale

IVIg works through multiple mechanisms to address antibody-mediated rejection (AMR):

• Neutralizes circulating donor-specific antibodies (DSAs)
• Blocks complement activation
• Modulates B-cell and T-cell responses
• Provides immunomodulatory effects on multiple components of the immune system

Treatment Protocols for AMR

Standard Combination Therapy

AMR in renal transplantation is rarely treated with IVIg monotherapy. The recommended approach involves:

1. First-line combination therapy:

   • Corticosteroids (methylprednisolone pulses)
   • Plasmapheresis to remove circulating antibodies
   • IVIg (1-2 g/kg divided into 2-4 doses)
   • Additional targeted agents based on severity 1

2. Dosing schedule:

   • IVIg typically administered after plasmapheresis sessions
   • Treatment frequency: 1-3 times weekly
   • Duration based on clinical response and DSA levels 1

Treatment Escalation for Refractory Cases

For cases not responding to standard therapy:

• Addition of rituximab (anti-CD20) to target B cells
• Bortezomib to target plasma cells
• In severe refractory cases, splenectomy may be considered as rescue therapy 2

Evidence Supporting IVIg Use

Multiple studies demonstrate the efficacy of IVIg in AMR:

• Cedars-Sinai reported successful treatment of antibody-mediated rejection with C4d deposition using high-dose IVIg (2 g/kg) in combination with pulse steroids, with 13 of 18 patients responding to treatment 3

• Case reports document successful rescue therapy with plasmapheresis and IVIg for acute humoral rejection, with good outcomes in graft function 4

• Treatment of late Class II antibody-mediated rejection has been achieved using IVIg in combination with either plasmapheresis or pulse steroids 5

Monitoring During Treatment

During IVIg therapy for AMR, monitor:

• Donor-specific antibody levels
• Renal function parameters
• Graft function via clinical assessment
• Adverse effects of IVIg (headache, fever, myalgia, volume overload)

Important Considerations and Cautions

• Potential adverse effects: Headache, chills, fever, myalgia, and volume overload may occur with IVIg infusion
• Premedication: Antihistamines and antipyretics may reduce infusion reactions
• Rare complications: In rare cases, IVIg preparations containing anti-HLA antibodies could potentially worsen AMR 6
• Cost considerations: IVIg is expensive compared to other rejection therapies and may have supply limitations 1

Treatment Algorithm for AMR in Renal Transplantation

1. Confirm diagnosis with biopsy (unless delay would harm patient)

2. Assess severity based on:

   • Presence of DSA
   • Degree of graft dysfunction
   • Histological findings

3. Initiate treatment based on severity:

   • Mild AMR: Pulse steroids + IVIg
   • Moderate to severe AMR: Pulse steroids + plasmapheresis + IVIg
   • Refractory AMR: Add rituximab or bortezomib to above regimen
   • Severe refractory AMR: Consider splenectomy as rescue therapy

4. Monitor response:

   • DSA levels
   • Renal function
   • Follow-up biopsies as needed

IVIg remains a cornerstone therapy in the management of antibody-mediated rejection in renal transplantation, but is most effective when used as part of a comprehensive treatment approach rather than as monotherapy.