title: Perioperative Desensitization Improves Outcomes Among Crossmatch Positive Recipients of Deceased Donor Renal Transplants.
abstract: BACKGROUND
  Graft failure due to chronic rejection is greater among renal transplant patients with donor-specific antibody (DSA) than among DSA-free patients. For patients dependent on deceased donor transplantation, preoperative desensitization to eliminate DSAs may be impractical. We speculated that perioperative desensitization might eliminate preexisting DSAs and prevent de novo DSAs and improve graft outcomes. We report that brief perioperative desensitization using either intravenous immunoglobulin (IVIG) or plasmapheresis/IVIG (PP/IVIG) treatment improves clinical outcomes among patients with positive crossmatches.
  
  
  METHODS
  Immediately following deceased donor transplantation, 235 renal recipients were assigned points for PRA and flow crossmatches (FCXM): delayed graft function (DGF) ≤ 1 point received standard therapy; 2 points received high-dose IVIG; and ≥3 points received PP/IVIG. The DSAs were serially monitored by single antigen bead luminex for 1 year. Five-year clinical outcomes were determined from the chart review.
  
  
  RESULTS
  All desensitized patients had preoperatively positive FCXM with DSA. Rejection was more common (P < .05) among desensitized than nonsensitized groups. However, overall graft survivals were similar between the groups (P = not significant) and superior to historic untreated patients (P < .05). Treatment with PP/IVIG more effectively eliminated preexisting DSAs (67% vs 33%, P < 0.05) than IVIG, but neither regimen prevented de novo formation of DSA (20%, P = not significant). Graft survival was >90% in all desensitizated patients with DSA elimination as well as PP/IVIG patients with residual DSA. In contrast, IVIG patients with persistent DSA had poorer graft survival (45%, P < .05).
  
  
  CONCLUSIONS
  Preemptive perioperative desensitization improved overall graft survival of sensitized patients compared to historic untreated patients. Plasmapheresis/IVIG had greater impact on DSA eradication and graft survival than IVIG alone.
authors.affiliation: Department of Transplant Surgery, Virginia Commonwealth University Hospitals, Richmond, VA, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Transplant Surgery, Virginia Commonwealth University Hospitals, Richmond, VA, USA Department of Internal Medicine, Virginia Commonwealth University Hospitals, Richmond, VA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: King
authors.affiliation: Department of Transplant Surgery, Virginia Commonwealth University Hospitals, Richmond, VA, USA Department of Internal Medicine, Virginia Commonwealth University Hospitals, Richmond, VA, USA.
authors.forename: Dhiren
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Transplant Surgery, Virginia Commonwealth University Hospitals, Richmond, VA, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Behnke
authors.affiliation: Department of Transplant Surgery, Virginia Commonwealth University Hospitals, Richmond, VA, USA.
authors.forename: Felecia
authors.initials: F
authors.lastname: McDougan
authors.affiliation: Department of Transplant Surgery, Virginia Commonwealth University Hospitals, Richmond, VA, USA pamela.kimball@vcuhealth.org.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Kimball
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002102:Cadaver; D015331:Cohort Studies; D051799:Delayed Graft Function; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006650:Histocompatibility Testing; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D019990:Perioperative Care / Q000379:methods*; D010956:Plasmapheresis / Q000379:methods*; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D000961:Antilymphocyte Serum; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D008776:Methylprednisolone Hemisuccinate; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: HLA antibodies; IVIG; desensitization; graft survival; renal transplant