Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation

Jennifer D Motter; Kyle R Jackson; Jane J Long; Madeleine M Waldram; Babak J Orandi; Robert A Montgomery; Mark D Stegall; Stanley C Jordan; Enrico Benedetti; Ty B Dunn; Lloyd E Ratner; Sandip Kapur; Ronald P Pelletier; John P Roberts; Marc L Melcher; Pooja Singh; Debra L Sudan; Marc P Posner; Jose M El-Amm; Ron Shapiro; Matthew Cooper; Jennifer E Verbesey; George S Lipkowitz; Michael A Rees; Christopher L Marsh; Bashir R Sankari; David A Gerber; Jason R Wellen; Adel Bozorgzadeh; A Osama Gaber; Eliot C Heher; Francis L Weng; Arjang Djamali; J Harold Helderman; Beatrice P Concepcion; Kenneth L Brayman; Jose Oberholzer; Tomasz Kozlowski; Karina Covarrubias; Allan B Massie; Dorry L Segev; Jacqueline M Garonzik-Wang

doi:10.1111/ajt.16471

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation

Am J Transplant. 2021 Apr;21(4):1612-1621. doi: 10.1111/ajt.16471. Epub 2021 Feb 27.

Authors

Jennifer D Motter¹, Kyle R Jackson¹, Jane J Long², Madeleine M Waldram¹, Babak J Orandi³, Robert A Montgomery⁴, Mark D Stegall², Stanley C Jordan⁵, Enrico Benedetti⁶, Ty B Dunn⁷, Lloyd E Ratner⁸, Sandip Kapur⁹, Ronald P Pelletier¹⁰, John P Roberts¹¹, Marc L Melcher¹², Pooja Singh¹³, Debra L Sudan¹⁴, Marc P Posner¹⁵, Jose M El-Amm¹⁶, Ron Shapiro¹⁷, Matthew Cooper¹⁸, Jennifer E Verbesey¹⁸, George S Lipkowitz¹⁹, Michael A Rees²⁰, Christopher L Marsh²¹, Bashir R Sankari²², David A Gerber²³, Jason R Wellen²⁴, Adel Bozorgzadeh²⁵, A Osama Gaber²⁶, Eliot C Heher²⁷, Francis L Weng²⁸, Arjang Djamali²⁹, J Harold Helderman³⁰, Beatrice P Concepcion³⁰, Kenneth L Brayman³¹, Jose Oberholzer³¹, Tomasz Kozlowski³², Karina Covarrubias³³, Allan B Massie¹, Dorry L Segev^{1

34

35}, Jacqueline M Garonzik-Wang¹

Affiliations

¹ Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.
³ Department of Surgery, University of Alabama, Birmingham, Alabama, USA.
⁴ New York University Langone Medical Center, The NYU Transplant Institute, New York, New York, USA.
⁵ Department of Medicine, Cedars-Sinai Comprehensive Transplant Center, Los Angeles, California, USA.
⁶ Department of Surgery, University of Illinois-Chicago, Chicago, Illinois, USA.
⁷ Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁸ Department of Surgery, Columbia University Medical Center, New York, New York, USA.
⁹ Department of Surgery, New York Presbyterian/Weill Cornell Medical Center, New York, New York, USA.
¹⁰ Department of Surgery, Robert Wood Johnson University Hospital, New Brunswick, New Jersey, USA.
¹¹ Department of Surgery, University of California-San Francisco, San Francisco, California, USA.
¹² Department of Surgery, Stanford University, Palo Alto, California, USA.
¹³ Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
¹⁴ Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
¹⁵ Department of Surgery, Virginia Commonwealth University, Richmond, Virginia, USA.
¹⁶ Integris Baptist Medical Center, Transplant Division, Oklahoma City, Oklahoma, USA.
¹⁷ Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, New York, USA.
¹⁸ Medstar Georgetown Transplant Institute, Washington, District of Columbia, USA.
¹⁹ Department of Surgery, Baystate Medical Center, Springfield, Massachusetts, USA.
²⁰ Department of Urology, University of Toledo Medical Center, Toledo, Ohio, USA.
²¹ Department of Surgery, Scripps Clinic and Green Hospital, La Jolla, California, USA.
²² Department of Urology, Cleveland Clinic, Cleveland, Ohio, USA.
²³ Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
²⁴ Department of Surgery, Barnes-Jewish Hospital, St. Louis, Missouri, USA.
²⁵ Department of Surgery, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts, USA.
²⁶ Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA.
²⁷ Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
²⁸ Renal and Pancreas Transplant Division, Saint Barnabas Medical Center, Livingston, New Jersey, USA.
²⁹ Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
³⁰ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³¹ Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.
³² Department of Surgery, University of Florida, Gainesville, Florida, USA.
³³ Department of Surgery, University of California San Diego, San Diego, California, USA.
³⁴ Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.
³⁵ Scientific Registry of Transplant Recipients, Minneapolis, Minnesota, USA.

Abstract

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = _1.03 1.68_2.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = _1.45 2.09_3.02 ; PFNC = _1.67 2.40_3.46 ; PCC = _1.48 2.24_3.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = _1.34 1.62_1.95 ) than CLDKT (aHR = _1.96 2.29_2.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Keywords: clinical research/practice; delayed graft function (DGF); desensitization; graft survival; histocompatibility; kidney transplantation/nephrology; patient survival; rejection: acute.

Publication types

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

MeSH terms

Delayed Graft Function / etiology
Graft Rejection / etiology
Graft Survival
Humans
Kidney Transplantation* / adverse effects
Living Donors
Retrospective Studies
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding