|Year : 2018 | Volume
| Issue : 3 | Page : 163-164
ABO-incompatible transplantation: A pipe dream to practice
Srikanth Gundlapalli, Girish Kumthekar
Department of Nephrologist, Care Hospital, Hyderabad, Telangana, India
|Date of Web Publication||28-Sep-2018|
Dr. Srikanth Gundlapalli
Department of Nephrologist, Care Hospital, Road No. 1, Banjara Hills, Hyderabad - 500 034, Telangana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gundlapalli S, Kumthekar G. ABO-incompatible transplantation: A pipe dream to practice. Indian J Transplant 2018;12:163-4
The burden of chronic kidney disease continues to increase in epidemic proportions. Renal transplantation remains the best modality of treatment to provide quality of life to these patients. Increasing organ shortage compelled the medical fraternity to innovate novel techniques. One revolutionary change has been a transformation of a historically contraindicated ABO-incompatible transplantation into a widely accepted modality, increasing the limited donor pool.
From the time Japanese pioneered large-scale ABO-incompatible transplantation in the 1980s to the present era, different protocols have evolved, but the following strategies form the cornerstone of all of them:
- Antibody depletion by plasmapheresis or immunoadsorption techniques
- Recipient immunomodulation using intravenous immunoglobulins
- B lymphocyte depletion by splenectomy (now obsolete) or rituximab
- Early institution of maintenance immunosuppression.
Rituximab inhibits new antibody production and prevents the rebound rise that occurs after antibody depletion. Antibody depletion is achieved by plasmapheresis or immunoadsorption based on the center protocol and experience. Plasmapheresis is further improvised after the innovation of double-filtration plasmapheresis (DFPP). DFPP was designed to selectively remove the immunoglobulin fraction from the serum and, as a result, minimize bleeding diathesis and the volume of substitution fluid required.
Subthreshold reduction of isoagglutinins for 2 weeks posttransplantation suffices in most cases. Accommodation (the graft phenomenon of resistance to circulating antibodies) seems to play the major role from thereon in preventing rejection, resulting in good long-term outcomes of these grafts. Local upregulation of complement regulatory proteins, such as CD45, CD55, and CD59, as a consequence of anti-A/B antibody-dependent inactivation of ERK1/2 signaling pathway, is discussed as one possible mechanism. Interestingly, A2 donors have low expression of antigens on their cell surfaces, facilitating transplantation with standard immunosuppressive therapy alone.
The costs and complexity of ABO incompatible transplantations are steadily coming down, though economic implications remain a significant barrier in the developing world. Even with the higher costs involving desensitization and induction protocols, renal transplantation from incompatible donors is more cost-effective than continuation of dialysis. Cost and infection risk in ABOi transplantation is further reduced by avoiding B-cell depletion with Rituximab. Instead iso-agglutinin removal is followed by induction and standard immunosuppression. A Japanese study proposes use of low dose Rituximab (100 mg) for recipients with low baseline iso-agglutinin titres. Among the living donor renal transplantations, if a compatible family donor is unavailable, kidney paired donations and altruistic donations are insufficient to sort the poor transplantation prospects of “O” group recipients and ABO-incompatible transplant remains the major hope for this set of patients.
Discard rates of kidneys from deceased A1B donors remains high even in experienced programs. ABO-incompatible transplantation from A1B donors is a feasible option to reduce this and increase transplantation options for a significant proportion of A and B waitlisted patients with low agglutinin titers.
Steroid-free and steroid-sparing protocols in some centers with ABO-incompatible transplants, have reported 1- and 3-year graft survival rates of 94% and 91% respectively. This facilitated minimization of steroid-related adverse effects in these patients.
The downside of these transplants includes the increased bleeding and surgical complications anticipated in view of plasmapheresis-induced coagulopathy, higher incidence of BK virus infections (hypothesized to be due to the binding of viral receptors to blood group antigens of renal tubular cells), and thrombotic microangiopathy. Thrombotic microangiopathy though uncommonly reported following ABO-incompatible transplantation entails a poor prognosis.
Overcoming this immunological barrier opened up the prospects for many potential recipients and improved our understanding of accommodation and tolerance. In this issue Jha et al. have highlighted their experience on ABOi transplants in Indian setting. Feasibility of xenotransplantation in the future though remains a matter of debate.
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