The Use of IVIG for Solid Organ Transplantation: An Evidence Based Practice Guideline

Background Utilization of intravenous immune globulin (IVIG) is increasing in Canada and worldwide despite few and no new labeled indications. In 2007, Canadian Blood Services in collaboration with the National Advisory Committee on Blood and Blood Products convened a panel of solid organ transplantation (SOT) experts (kidney, heart, lung, and liver) and methodologists to develop an evidence-based practice guideline for the use of IVIG in patients undergoing SOT. The objectives of this guideline are

1. to examine the evidence for the use of IVIG in patients who are candidates for SOT and are sensitized to HLA or ABO antigens,

2. to provide guidance for Canadian practitioners involved in the care of these patients and transfusion medicine specialists on the use of IVIG.

Methods: The panel identified clinical areas of SOT that would benefit from treatment with IVIG and generated key clinical questions. A systematic, expert and bibliography literature search up to July 2008 was conducted to ensure all relevant publications were included. The panel generated recommendations based on the evidence. The levels of evidence and grading of recommendations were adapted from the Canadian Task Force on Preventative Health Care. To validate conclusions and recommendations, the practice guideline will be sent to physicians involved in solid organ transplantation in Canada and a patient representative. Recommendations from practitioner feedback will be incorporated, and the guideline will be disseminated to all physicians involved in the care of patients receiving solid organ transplantation in Canada to aid implementation of the guideline. The National Advisory Committee of Blood and Blood Products in Canada will subsequently assess the performance of the guideline and will renew the guideline at timely intervals.

Results and Conclusions: The research questions developed by the panel were: Is there evidence that the use of IVIG reduces morbidity and mortality for patients undergoing SOT who are

1. sensitized (HLA or ABO)

2. in the perioperative setting and are sensitized

3. experiencing acute graft rejection or

4. experiencing chronic graft rejection? 791 citations were retrieved, and panel members identified 3 additional citations.

51 reports and a systematic review were used for this guideline. These reports were limited by inconsistent definitions of sensitization, inconsistent reporting of the type and titre of the antibody, the assays used to detect HLA antibodies, the response criteria and dosing schedules for IVIG. Thus, a consensus process was used to account for the poor evidence. The use of IVIG was associated with decreased sensitization and acceptable morbidity and mortality in living donor kidney transplantation. IVIG has been used with several other modalities for ABO-incompatible kidney transplantation and it was difficult from the existing literature to separate outcomes based on a single modality. There was also limited data on the perioperative use of IVIG in renal transplantation. IVIG was shown to be effective in combination with plasmapheresis for acute antibody mediated rejection of the kidney; however the role of IVIG was not clear for other forms of rejection. There were also several methodological limitations in the literature assessing IVIG for cardiac transplantation and only limited data were available to assess the use of IVIG for lung or liver transplantation. Future studies are needed to define the role of IVIG in solid organ transplantation and should capture the following elements: impact on antibody (specificity and titres), transplant rates, time to transplantation, graft function, graft survival, and rejection (cellular and antibody mediated).