Immunogenetics & Transplantation -Clinical Transplantation

Introduction
Organ transplants are in widespread use. Limitations include the scarcity of donor organs and expense. Failure to achieve successful grafts is primarily due to histoincompatibility and lack of safe and effective immunosuppressive regimens to halt rejection. Avoiding transmission of infectious agents (eg, HIV, HBV, HCV, CMV) from donor to recipient requires extensive pretransplant serologic testing.

Kidney Transplantation

End-stage renal disease is the indication for kidney transplantation. Factors that determine outcome include antigenic disparity (ABO blood groups and major histocompatibility or HLA) between donor and recipient, the type of immunologic response mounted by the host, and the immunosuppressive regimen used to prevent graft rejection. Nonimmunologic factors that affect the risk of chronic rejection include age and race of recipient, donor age, length of time on dialysis, and coexisting hyperlipidemia, hypertension, or cytomegalovirus infection.

Kidneys from living related donors who are HLA-identical and also red cell ABO-matched grafts have 90% survival at 1 year; grafts from less-well matched relatives and from living unrelated donors have lower rates. Antigens are matched for HLA-A, -B and -DR loci, with -DR compatibility most important for long-term graft survival. Grafts from cadaver donors with zero HLA mismatches have a half-life of 11.3 years. Those with six mismatches have a half-life of 6.8 years, compared with those from HLA-identical siblings, which have a half-life of 23.6 years.

Some donors are highly sensitized to HLA antigens from previous transfusions, ie, possess high panel reactive antibody levels. It may be difficult to find a suitable donor, since a positive cross-match by cytotoxicity testing is likely and would be a contraindication to transplant. Donor screening is performed in all cases to assess suitability, rule out hypertension or anatomic anomalies, and avoid transmission of hepatitis viruses, HIV, and other infectious agents. Owing to the scarcity of related donors, living unrelated donors may be used in certain circumstances. Pretreatment of recipients with blood transfusions from the donor appears to extend graft survival even longer.

Delayed allograft function can be due to hyperacute graft rejection, post ischemic acute tubular necrosis, cyclosporine toxicity, or obstructive nephropathy. If conservative measures do not improve function or patients are at high risk of allograft rejection, renal biopsy should be performed for definitive diagnostic purposes. Renal allograft rejection may be due to hyperacute rejection from binding of cytotoxic antibodies and complement activation, acute rejection from cellular immune responses, or chronic rejection. A form of interstitial nephritis secondary to polyomavirus infection is associated with aggressive immunosuppression.