Induction and Donor Specific Antibodies in Low Immunologic Risk Kidney Transplant Recipients

Overview

Journal Kidney360

Specialty Nephrology

Date 2022 Apr 4

PMID 35372884

Authors

Natalie M Bath

Arjang Djamali

Sandesh Parajuli

Didier Mandelbrot

Glen Leverson

Luis Hidalgo

Thomas Ellis

Jillian L Descourouez

Margaret R Jorgenson

Dave Hager

Dixon B Kaufman

Robert R Redfield 3rd

Affiliations

Soon will be listed here.

Abstract

Background: Optimal induction for patients without pretransplant donor-specific antibodies (DSAs) is poorly defined. The goal of this study was to compare the incidence of DSA (dnDSA) and graft outcomes between induction therapies in patients with a negative virtual crossmatch (VXM).

Methods: A retrospective chart review was performed, identifying 782 patients with a negative VXM who underwent kidney transplantation at a single, high-volume institution between January 2013 and May 2017. Kaplan-Meier analysis was used to assess the incidence of dnDSA and allograft survival between induction therapies in this group. dnDSA is defined as the development of new post-transplant DSA, at any MFI level.

Results: Induction therapy included alemtuzumab (=87, 11%), basiliximab (=522, 67%), and anti-thymocyte globulin (ATG; =173, 22%). One-year graft survival was similar between groups (alemtuzumab, 100%; basiliximab, 98%; ATG, 99%). Incidence of acute rejection at 1 year was <2% and not different between the three groups. Alemtuzumab was associated with the highest incidence of dnDSA at 14%, compared with 5% and 8% in basiliximab and ATG groups, respectively, at 1 year (=0.009). In multivariate regression analyses, alemtuzumab retained its significant association with a dnDSA HR of 2.5 (95% CI, 1.51 to 4.25; =0.0004).

Conclusions: In summary, alemtuzumab was associated with a higher rate of dnDSA development in patients with a negative VXM; however, this finding was not associated with rejection or graft failure.

Citing Articles

Allogeneic HLA Humoral Immunogenicity and the Prediction of Donor-Specific HLA Antibody Development.

Jucaud V Antibodies (Basel). 2024; 13(3).

PMID: 39189232 PMC: 11348167. DOI: 10.3390/antib13030061.

Everolimus plus reduced calcineurin inhibitor prevents anti-HLA antibodies and humoral rejection in kidney transplant recipients: 12-month results from the ATHENA study.

Arns W, Philippe A, Ditt V, Hauser I, Thaiss F, Sommerer C Front Transplant. 2024; 2:1264903.

PMID: 38993866 PMC: 11235221. DOI: 10.3389/frtra.2023.1264903.

References

Lee P, Terasaki P, Takemoto S, Lee P, Hung C, Chen Y . All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies. Transplantation. 2002; 74(8):1192-4. DOI: 10.1097/00007890-200210270-00025. View

Parajuli S, Joachim E, Alagusundaramoorthy S, Blazel J, Aziz F, Garg N . Subclinical Antibody-mediated Rejection After Kidney Transplantation: Treatment Outcomes. Transplantation. 2018; 103(8):1722-1729. DOI: 10.1097/TP.0000000000002566. View

Goggins W, Pascual M, Powelson J, Magee C, Tolkoff-Rubin N, Farrell M . A prospective, randomized, clinical trial of intraoperative versus postoperative Thymoglobulin in adult cadaveric renal transplant recipients. Transplantation. 2003; 76(5):798-802. DOI: 10.1097/01.TP.0000081042.67285.91. View

Wiendl H, Kieseier B . Multiple sclerosis: reprogramming the immune repertoire with alemtuzumab in MS. Nat Rev Neurol. 2013; 9(3):125-6. DOI: 10.1038/nrneurol.2013.2. View

Gaber A, Knight R, Patel S, Gaber L . A review of the evidence for use of thymoglobulin induction in renal transplantation. Transplant Proc. 2010; 42(5):1395-400. DOI: 10.1016/j.transproceed.2010.04.019. View

Brennan D, Schnitzler M . Long-term results of rabbit antithymocyte globulin and basiliximab induction. N Engl J Med. 2008; 359(16):1736-8. DOI: 10.1056/NEJMc0805714. View

Worthington J, Martin S, Al-Husseini D, Dyer P, Johnson R . Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome. Transplantation. 2003; 75(7):1034-40. DOI: 10.1097/01.TP.0000055833.65192.3B. View

Parajuli S, Mandelbrot D, Muth B, Mohamed M, Garg N, Aziz F . Rituximab and Monitoring Strategies for Late Antibody-Mediated Rejection After Kidney Transplantation. Transplant Direct. 2018; 3(12):e227. PMC: 5828696. DOI: 10.1097/TXD.0000000000000746. View

Lebranchu Y, Bridoux F, Buchler M, Le Meur Y, Etienne I, Toupance O . Immunoprophylaxis with basiliximab compared with antithymocyte globulin in renal transplant patients receiving MMF-containing triple therapy. Am J Transplant. 2002; 2(1):48-56. DOI: 10.1034/j.1600-6143.2002.020109.x. View

10.

Sollinger H, Kaplan B, Pescovitz M, Philosophe B, Roza A, Brayman K . Basiliximab versus antithymocyte globulin for prevention of acute renal allograft rejection. Transplantation. 2002; 72(12):1915-9. DOI: 10.1097/00007890-200112270-00008. View

11.

Brokhof M, Sollinger H, Hager D, Muth B, Pirsch J, Fernandez L . Antithymocyte globulin is associated with a lower incidence of de novo donor-specific antibodies in moderately sensitized renal transplant recipients. Transplantation. 2014; 97(6):612-7. PMC: 4106033. DOI: 10.1097/TP.0000000000000031. View

12.

Hart A, Smith J, Skeans M, Gustafson S, Wilk A, Robinson A . OPTN/SRTR 2016 Annual Data Report: Kidney. Am J Transplant. 2018; 18 Suppl 1:18-113. PMC: 5772947. DOI: 10.1111/ajt.14557. View

13.

Knechtle S, Pirsch J, Fechner Jr J, Becker B, Friedl A, Colvin R . Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study. Am J Transplant. 2003; 3(6):722-30. DOI: 10.1034/j.1600-6143.2003.00120.x. View

14.

Brennan D, Daller J, Lake K, Cibrik D, Del Castillo D . Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med. 2006; 355(19):1967-77. DOI: 10.1056/NEJMoa060068. View

15.

Charpentier B, Rostaing L, Berthoux F, Lang P, Civati G, Touraine J . A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients. Transplantation. 2003; 75(6):844-51. DOI: 10.1097/01.TP.0000056635.59888.EF. View

16.

Djamali A, Muth B, Ellis T, Mohamed M, Fernandez L, Miller K . Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients. Kidney Int. 2013; 83(6):1185-92. PMC: 3672254. DOI: 10.1038/ki.2013.44. View

17.

Terasaki P, Ozawa M, Castro R . Four-year follow-up of a prospective trial of HLA and MICA antibodies on kidney graft survival. Am J Transplant. 2007; 7(2):408-15. DOI: 10.1111/j.1600-6143.2006.01644.x. View

18.

Wiebe C, Gibson I, Blydt-Hansen T, Karpinski M, Ho J, Storsley L . Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant. 2012; 12(5):1157-67. DOI: 10.1111/j.1600-6143.2012.04013.x. View

19.

Terasaki P . Humoral theory of transplantation. Am J Transplant. 2003; 3(6):665-73. DOI: 10.1034/j.1600-6143.2003.00135.x. View

20.

Ruck T, Bittner S, Wiendl H, Meuth S . Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond. Int J Mol Sci. 2015; 16(7):16414-39. PMC: 4519957. DOI: 10.3390/ijms160716414. View