Transplanting Sensitized Kidney Transplant Patients With Equivalent Outcomes Utilizing Stringent HLA Crossmatching

Exp Clin Transplant. 2017 Feb;15(1):47-55. doi: 10.6002/ect.2015.0274. Epub 2016 Jun 3.

Abstract

Objecives: Elevated panel reactive antibody levels have been traditionally associated with increased acute rejection rate and decreased long-term graft survival after kidney transplant. In this study, our objective was to determine patient and allograft outcomes in sensitized kidney transplant recipients with advanced HLA antibody detection and stringent protein sequence epitope analyses.

Materials and methods: This was a subanalysis of a prospective, risk-stratified randomized controlled trial that compared interleukin 2 receptor antagonist to rabbit antithymocyte globulin induction in 200 kidney transplant recipients, examining outcomes based on panel reactive antibody levels of < 20% (low) versus ≥ 20% (high, sensitized). The study was conducted between February 2009 and July 2011. All patients underwent solid-phase single antigen bead assays to detect HLA antibodies and stringent HLA epitope analyses with protein sequence alignment for virtual crossmatching. Delayed graft function, acute rejection rates, and graft loss were the main outcomes measured.

Results: Both the low (134 patients) and high (66 patients) panel reactive antibody level cohorts had equivalent induction and maintenance immunosuppression. Patients in the high-level group were more likely to be female (P < .001), African American (P < .001), and received a kidney from a deceased donor (P = .004). Acute rejection rates were similar between the low (rate of 8%) and high (rate of 9%) panel reactive antibody groups (P = .783). Delayed graft function, borderline rejection, graft loss, and death were not different between groups. Multivariate analyses demonstrated delayed graft function to be the strongest predictor of acute rejection (odds ratio, 5.7; P = .005); panel reactive antibody level, as a continuous variable, had no significant correlation with acute rejection (C statistic, 0.48; P = .771).

Conclusions: Appropriate biologic matching with single antigen bead assays and stringent epitope analyses provided excellent outcomes in sensitized patients regardless of the induction therapy choice.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Antilymphocyte Serum / therapeutic use
  • Area Under Curve
  • Biomarkers / blood
  • Chi-Square Distribution
  • Delayed Graft Function / etiology
  • Drug Therapy, Combination
  • Epitopes*
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival
  • HLA Antigens / immunology*
  • Histocompatibility Testing / methods*
  • Histocompatibility*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Isoantibodies / blood*
  • Kaplan-Meier Estimate
  • Kidney Transplantation* / adverse effects
  • Kidney Transplantation* / mortality
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Receptors, Interleukin-2 / antagonists & inhibitors
  • Receptors, Interleukin-2 / immunology
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Antilymphocyte Serum
  • Biomarkers
  • Epitopes
  • HLA Antigens
  • Immunosuppressive Agents
  • Isoantibodies
  • Receptors, Interleukin-2
  • thymoglobulin