Desensitization in HLA-incompatible Kidney Recipients and Survival

N Engl J Med. 2011 Jul 28;365(4):318-26. doi: 10.1056/NEJMoa1012376.

Abstract

Background: More than 20,000 candidates for kidney transplantation in the United States are sensitized to HLA and may have a prolonged wait for a transplant, with a reduced transplantation rate and an increased rate of death. One solution is to perform live-donor renal transplantation after the depletion of donor-specific anti-HLA antibodies. Whether such antibody depletion results in a survival benefit as compared with waiting for an HLA-compatible kidney is unknown.

Methods: We used a protocol that included plasmapheresis and the administration of low-dose intravenous immune globulin to desensitize 211 HLA-sensitized patients who subsequently underwent renal transplantation (treatment group). We compared rates of death between the group undergoing desensitization treatment and two carefully matched control groups of patients on a waiting list for kidney transplantation who continued to undergo dialysis (dialysis-only group) or who underwent either dialysis or HLA-compatible transplantation (dialysis-or-transplantation group).

Results: In the treatment group, Kaplan-Meier estimates of patient survival were 90.6% at 1 year, 85.7% at 3 years, 80.6% at 5 years, and 80.6% at 8 years, as compared with rates of 91.1%, 67.2%, 51.5%, and 30.5%, respectively, for patients in the dialysis-only group and rates of 93.1%, 77.0%, 65.6%, and 49.1%, respectively, for patients in the dialysis-or-transplantation group (P<0.001 for both comparisons).

Conclusions: Live-donor transplantation after desensitization provided a significant survival benefit for patients with HLA sensitization, as compared with waiting for a compatible organ. By 8 years, this survival advantage more than doubled. These data provide evidence that desensitization protocols may help overcome incompatibility barriers in live-donor renal transplantation. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Charles T. Bauer Foundation.).

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Desensitization, Immunologic / methods*
  • Female
  • Histocompatibility Testing
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney Failure, Chronic / surgery*
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / mortality
  • Living Donors
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Plasmapheresis* / adverse effects
  • Renal Dialysis
  • Tacrolimus / therapeutic use
  • Transplantation Conditioning / methods
  • Transplantation Immunology

Substances

  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus