Impact of Donor-Specific Antibodies in (Highly-) Immunized Living Donor Kidney Transplant Recipients

NCT ID: NCT05431712

Last Updated: 2024-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

252 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-01-01

Study Completion Date

2019-12-31

Brief Summary

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Kidney transplantation is the preferred treatment for end-stage renal disease. Alongside limited availability of donors, rejection and premature graft loss are main barriers to kidney transplantation. Donor-specific antibodies pre-transplantation may arise due to to prior solid organ transplantation, pregnancy or blood transfusions. Their presence is considered a risk of graft failure. The impact of DSA is differently reported in literature, also according to the technique by which DSA have been measured. Techniques such as the complement-dependent cytotoxicity crossmatch, the immunofluorescence crossmatch and the Luminex Single Antigen Bead have different sensitivities for detecting DSA.

Historically, our kidney transplant program has been advocating living donor transplantation and as a result the majority of transplantations are with a living donor. In this context and in the absence of a compatible living donor, pretransplant DSA have not been considered an absolute contra-indication for transplantation. The aim of the current study is to determine the effect of DSAs on rejection and death-censored graft survival in living donor kidney transplantation.

Participants are adults who underwent a living donor kidney transplantation between 2010 and 2019 in the presence of DSA. Control subjects are both immunized and non-immunized kidney transplant recipients in the same period.

This is a retrospective, case control study. Death-censored graft survival is analyzed for all patients and compared by presence of DSA and other predicting variables, such as immunization level, age, sex and HLA mismatches. Furthermore, biopsy proven rejection, patient survival, kidney function, length of hospital stay and proteinuria are analyzed.

Also, a predefined subgroup analysis is performed in the DSA positive patients. These are compared according to amount, strength and HLA-class of DSAs.

Detailed Description

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Conditions

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Renal Failure

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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DSA+

Patients with pre-transplantation detected donor-specific antibodies, with Luminex Single Antigen Bead analysis.

No interventions assigned to this group

PRA+

Immunized controls without DSAs pre-transplantation, with equal peak PRA levels and donor/recipient age as the DSA+ group.

No interventions assigned to this group

PRA-

Non-immunized controls without DSAs pre-transplantation, with a peak PRA of less than 6%, with equal donor/recipient age as the DSA+ group.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Pre-transplantation donor-specific antibodies in Luminex Single Antigen Bead analysis.
* Age 18 years or older

Exclusion Criteria

* Desensitization treatment for a current or historic positive CDC-crossamtch
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Erasmus Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Annelies de Weerd, MD, PhD

MD, PhD, Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

References

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Chung BH, Choi BS, Oh EJ, Park CW, Kim JI, Moon IS, Kim YS, Yang CW. Clinical impact of the baseline donor-specific anti-human leukocyte antigen antibody measured by Luminex single antigen assay in living donor kidney transplant recipients after desensitization therapy. Transpl Int. 2014 Jan;27(1):49-59. doi: 10.1111/tri.12199. Epub 2013 Oct 25.

Reference Type BACKGROUND
PMID: 24118413 (View on PubMed)

Betjes MGH, Sablik KS, Otten HG, Roelen DL, Claas FH, de Weerd A. Pretransplant Donor-Specific Anti-HLA Antibodies and the Risk for Rejection-Related Graft Failure of Kidney Allografts. J Transplant. 2020 Jan 29;2020:5694670. doi: 10.1155/2020/5694670. eCollection 2020.

Reference Type BACKGROUND
PMID: 32099669 (View on PubMed)

Kamburova EG, Wisse BW, Joosten I, Allebes WA, van der Meer A, Hilbrands LB, Baas MC, Spierings E, Hack CE, van Reekum FE, van Zuilen AD, Verhaar MC, Bots ML, Drop ACAD, Plaisier L, Seelen MAJ, Sanders JSF, Hepkema BG, Lambeck AJA, Bungener LB, Roozendaal C, Tilanus MGJ, Voorter CE, Wieten L, van Duijnhoven EM, Gelens M, Christiaans MHL, van Ittersum FJ, Nurmohamed SA, Lardy NM, Swelsen W, van der Pant KA, van der Weerd NC, Ten Berge IJM, Bemelman FJ, Hoitsma A, van der Boog PJM, de Fijter JW, Betjes MGH, Heidt S, Roelen DL, Claas FH, Otten HG. Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant. Am J Transplant. 2018 Sep;18(9):2274-2284. doi: 10.1111/ajt.14709. Epub 2018 Apr 16.

Reference Type BACKGROUND
PMID: 29464832 (View on PubMed)

Ziemann M, Altermann W, Angert K, Arns W, Bachmann A, Bakchoul T, Banas B, von Borstel A, Budde K, Ditt V, Einecke G, Eisenberger U, Feldkamp T, Gorg S, Guthoff M, Habicht A, Hallensleben M, Heinemann FM, Hessler N, Hugo C, Kaufmann M, Kauke T, Koch M, Konig IR, Kurschat C, Lehmann C, Marget M, Muhlfeld A, Nitschke M, Pego da Silva L, Quick C, Rahmel A, Rath T, Reinke P, Renders L, Sommer F, Spriewald B, Staeck O, Stippel D, Susal C, Thiele B, Zecher D, Lachmann N. Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation: A Multicenter Study. Clin J Am Soc Nephrol. 2019 Jul 5;14(7):1056-1066. doi: 10.2215/CJN.13401118. Epub 2019 Jun 18.

Reference Type BACKGROUND
PMID: 31213508 (View on PubMed)

Orandi BJ, Garonzik-Wang JM, Massie AB, Zachary AA, Montgomery JR, Van Arendonk KJ, Stegall MD, Jordan SC, Oberholzer J, Dunn TB, Ratner LE, Kapur S, Pelletier RP, Roberts JP, Melcher ML, Singh P, Sudan DL, Posner MP, El-Amm JM, Shapiro R, Cooper M, Lipkowitz GS, Rees MA, Marsh CL, Sankari BR, Gerber DA, Nelson PW, Wellen J, Bozorgzadeh A, Gaber AO, Montgomery RA, Segev DL. Quantifying the risk of incompatible kidney transplantation: a multicenter study. Am J Transplant. 2014 Jul;14(7):1573-80. doi: 10.1111/ajt.12786. Epub 2014 Jun 9.

Reference Type BACKGROUND
PMID: 24913913 (View on PubMed)

Orandi BJ, Luo X, Massie AB, Garonzik-Wang JM, Lonze BE, Ahmed R, Van Arendonk KJ, Stegall MD, Jordan SC, Oberholzer J, Dunn TB, Ratner LE, Kapur S, Pelletier RP, Roberts JP, Melcher ML, Singh P, Sudan DL, Posner MP, El-Amm JM, Shapiro R, Cooper M, Lipkowitz GS, Rees MA, Marsh CL, Sankari BR, Gerber DA, Nelson PW, Wellen J, Bozorgzadeh A, Gaber AO, Montgomery RA, Segev DL. Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors. N Engl J Med. 2016 Mar 10;374(10):940-50. doi: 10.1056/NEJMoa1508380.

Reference Type BACKGROUND
PMID: 26962729 (View on PubMed)

Jordan SC, Lorant T, Choi J, Kjellman C, Winstedt L, Bengtsson M, Zhang X, Eich T, Toyoda M, Eriksson BM, Ge S, Peng A, Jarnum S, Wood KJ, Lundgren T, Wennberg L, Backman L, Larsson E, Villicana R, Kahwaji J, Louie S, Kang A, Haas M, Nast C, Vo A, Tufveson G. IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation. N Engl J Med. 2017 Aug 3;377(5):442-453. doi: 10.1056/NEJMoa1612567.

Reference Type BACKGROUND
PMID: 28767349 (View on PubMed)

Other Identifiers

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MEC-2021-0357

Identifier Type: -

Identifier Source: org_study_id

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