Quantifying the Risk of Incompatible Kidney Transplantation: A Multicenter Study

Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti‐HLA donor‐specific antibody (DSA). Program‐specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15–2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71–6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28–3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98–7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal‐quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19‐, 1.33‐ and 1.73‐fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22‐, 4.09‐ and 10.72‐fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life‐saving treatment in jeopardy of regulatory intervention.

[1]  D. Gjertson,et al.  Kidney paired donation in the presence of donor-specific antibodies. , 2013, Kidney international.

[2]  T. Ellis.  Interpretation of HLA single antigen bead assays. , 2013, Transplantation reviews.

[3]  D. Segev,et al.  Rates of False Flagging Due to Statistical Artifact in CMS Evaluations of Transplant Programs: Results of a Stochastic Simulation , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[4]  P S Heeger,et al.  Comprehensive Assessment and Standardization of Solid Phase Multiplex‐Bead Arrays for the Detection of Antibodies to HLA , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[5]  H. Al Mana,et al.  Outcome of desensitization in human leukocyte antigen- and ABO-incompatible living donor kidney transplantation: a single-center experience in more than 100 patients. , 2013, Transplantation proceedings.

[6]  A. Webster,et al.  Consensus Guidelines on the Testing and Clinical Management Issues Associated With HLA and Non-HLA Antibodies in Transplantation , 2013, Transplantation.

[7]  M. Stegall,et al.  Five‐Year Outcomes in Living Donor Kidney Transplants With a Positive Crossmatch , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[8]  M. Zeier,et al.  Living donor kidney transplantation in patients with donor-specific HLA antibodies enabled by anti-CD20 therapy and peritransplant apheresis. , 2013, Atherosclerosis. Supplements.

[9]  C. Sommerer,et al.  Living donor kidney transplantation in crossmatch‐positive patients enabled by peritransplant immunoadsorption and anti‐CD20 therapy , 2012, Transplant international : official journal of the European Society for Organ Transplantation.

[10]  A. Zachary,et al.  HLA antibody detection and characterization by solid phase immunoassays: methods and pitfalls. , 2012, Methods in molecular biology.

[11]  R. Higgins,et al.  Human Leukocyte Antigen Antibody-Incompatible Renal Transplantation: Excellent Medium-Term Outcomes With Negative Cytotoxic Crossmatch , 2011, Transplantation.

[12]  T. Pruett,et al.  Revisiting Traditional Risk Factors for Rejection and Graft Loss After Kidney Transplantation , 2011, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  L. Kucirka,et al.  Incompatible live-donor kidney transplantation in the United States: results of a national survey. , 2011, Clinical journal of the American Society of Nephrology : CJASN.

[14]  R. Montgomery,et al.  Using donor exchange paradigms with desensitization to enhance transplant rates among highly sensitized patients , 2011, Current opinion in organ transplantation.

[15]  L. Kucirka,et al.  Desensitization in HLA-incompatible kidney recipients and survival. , 2011, The New England journal of medicine.

[16]  M. Mihatsch,et al.  Efficacy of Induction Therapy with ATG and Intravenous Immunoglobulins in Patients with Low‐Level Donor‐Specific HLA‐Antibodies , 2010, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[17]  Walter K. Kremers,et al.  Baseline Donor‐Specific Antibody Levels and Outcomes in Positive Crossmatch Kidney Transplantation , 2010, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[18]  E. Thervet,et al.  Outcome of Subclinical Antibody‐Mediated Rejection in Kidney Transplant Recipients with Preformed Donor‐Specific Antibodies , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[19]  A. Zachary,et al.  Naturally occurring interference in Luminex assays for HLA-specific antibodies: characteristics and resolution. , 2009, Human immunology.

[20]  S. Jacobs,et al.  Positive Cross‐Match Living Donor Kidney Transplantation: Longer‐Term Outcomes , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[21]  C. Hughes,et al.  Excellent Renal Allograft Survival in Donor-Specific Antibody Positive Transplant Patients—Role of Intravenous Immunoglobulin and Rabbit Antithymocyte Globulin , 2009, Transplantation.

[22]  E. Benedetti,et al.  Living Donor Kidney Transplantation Across Positive Crossmatch: The University of Illinois at Chicago Experience , 2009, Transplantation.

[23]  M. Stegall,et al.  Alloantibody Levels and Acute Humoral Rejection Early After Positive Crossmatch Kidney Transplantation , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[24]  S. Jordan,et al.  Rituximab and intravenous immune globulin for desensitization during renal transplantation. , 2008, The New England journal of medicine.

[25]  C. Magee,et al.  Renal Transplantation in Patients With Positive Lymphocytotoxicity Crossmatches: One Center’s Experience , 2008, Transplantation.

[26]  A. Wiseman,et al.  Detection of donor-specific antibodies using HLA-coated microspheres: another tool for kidney transplant risk stratification. , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[27]  M. Stegall,et al.  A Comparison of Plasmapheresis Versus High‐Dose IVIG Desensitization in Renal Allograft Recipients with High Levels of Donor Specific Alloantibody , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[28]  D. Dykstra,et al.  Transplant data: sources, collection and research considerations, 2004 , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[29]  J. Bromberg,et al.  Intravenous immunoglobulin induction treatment in flow cytometry cross-match-positive kidney transplant recipients. , 2005, Human immunology.

[30]  J. Bromberg,et al.  Intravenous immunoglobulin and thymoglobulin facilitate kidney transplantation in complement-dependent cytotoxicity B-cell and flow cytometry T- or B-cell crossmatch-positive patients , 2003, Transplantation.

[31]  T. Larson,et al.  Overcoming a Positive Crossmatch in Living‐Donor Kidney Transplantation , 2003, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[32]  J. Bariéty,et al.  Desensitization and Subsequent Kidney Transplantation of Patients Using Intravenous Immunoglobulins (IVIg) , 2002, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[33]  M. Fernandez-Vina,et al.  A HIGH PANEL-REACTIVE ANTIBODY RESCUE PROTOCOL FOR CROSS-MATCH-POSITIVE LIVE DONOR KIDNEY TRANSPLANTS1 , 2000, Transplantation.

[34]  R. Montgomery,et al.  PLASMAPHERESIS AND INTRAVENOUS IMMUNE GLOBULIN PROVIDES EFFECTIVE RESCUE THERAPY FOR REFRACTORY HUMORAL REJECTION AND ALLOWS KIDNEYS TO BE SUCCESSFULLY TRANSPLANTED INTO CROSS-MATCH-POSITIVE RECIPIENTS , 2000, Transplantation.

[35]  P. Padfield,et al.  Renal , 1999, Diabetic medicine : a journal of the British Diabetic Association.

[36]  A. Zachary,et al.  VARIATIONS OF THE LYMPHOCYTOTOXICITY TEST AN EVALUATION OF SENSITIVITY AND SPECIFICITY , 1995, Transplantation.

[37]  L. Czer,et al.  Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. , 1994, Transplantation.