Greater Impact of Living Donation Than HLA Mismatching in Short-Term Renal Allograft Survival

Overview

Journal Cureus

Specialty Biomedical Engineering

Date 2023 Feb 3

PMID 36733571

Authors

Barbara Ribeiro

Pedro Reis Pereira

Joao Oliveira

Manuela Almeida

La Salete Martins

Jorge Malheiro

Affiliations

Soon will be listed here.

Abstract

Introduction: Living donor kidney transplantation (LDKT) is accepted as first-line treatment for patients with end-stage kidney disease with advantages over deceased donor kidney transplantation (DDKT). Still, how the known detrimental effect of HLA mismatch (MM) may hamper these advantages remains unsettled. We sought to determine the effect of the degree of HLA MM, separately in deceased and living donor renal allograft outcomes.

Methods: We evaluated all adults submitted to LDKT and DDKT at our center between 2006 and 2018. Their HLA MM was classified according to the British Society of Transplantation system in low mismatch (LM) (level 1-2) and high mismatch (HM) (level 3-4). Acute rejection (AR) and global or censored graft survival were the outcomes of interest. Recipients were followed up from transplant until death, graft failure or the end of 2020. Results: One thousand sixty-eight kidney transplant recipients were analyzed, 815 (76%) received a DDKT whereas 253 (24%) received an LDKT. From those submitted to DDKT, 95 (12%) had an LM and 720 (88%) had an HM, whereas in LDKT 32 (13%) had an LM and 221 (87%) had an HM. The AR at one year was 9% in the full cohort. Significant risk factors for AR were HM DDKT (OR:2.3, P=0.047) or HM LDKT (OR:5.6, P=0.003) (LM DDKT as reference), calculated panel-reactive antibody (cPRA) ≥5% (OR:1.9, P=0.040) and delayed graft function (DGF), (OR:3.2, P<0.001). Censored graft survival (CGS) at five years was 96% in the full cohort. Independent predictors for censored graft failure (CGF) were HM LDKT (HR:0.2, P=0.046) (LM DDKT as reference), AR (HR:2.7, P=0.008) and DGF (HR:2.2, P=0.017). Global graft survival (GGS) at five years was 91% in the full cohort. Independent predictors for global graft failure (GGF) were HM LDKT (HR:0.2, P=0.042) (LM DDKT as reference), recipient age (HR:1.8, P<0.001) and DGF (HR:1.8, P=0.006). No AR, CGF or GGF episodes were observed in the LM LDKT group.

Conclusions: In our cohort, the level of HLA MM increased the risk of AR independently of donor type. Considering short graft survival, our results support the advantage of living donor vs deceased donor even with an increased HLA MM. However, its effect on long-term graft survival remains to be settled, emphasizing the need for further studies on this matter.

References

Williams R, Opelz G, Weil E, McGarvey C, Chakkera H . The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide. Transplant Direct. 2017; 3(5):e152. PMC: 5441983. DOI: 10.1097/TXD.0000000000000664. View

Papalois V, Moss A, Gillingham K, Sutherland D, Matas A, Humar A . Pre-emptive transplants for patients with renal failure: an argument against waiting until dialysis. Transplantation. 2000; 70(4):625-31. DOI: 10.1097/00007890-200008270-00016. View

Castro A, Malheiro J, Tafulo S, Dias L, Martins L, Fonseca I . Role of de novo donor-specific anti-HLA antibodies in kidney graft failure: A case-control study. HLA. 2017; 90(5):267-275. DOI: 10.1111/tan.13111. View

Meier-Kriesche H, Scornik J, Susskind B, Rehman S, Schold J . A lifetime versus a graft life approach redefines the importance of HLA matching in kidney transplant patients. Transplantation. 2009; 88(1):23-9. DOI: 10.1097/TP.0b013e3181a9ec89. View

Casey M, Wen X, Rehman S, Santos A, Andreoni K . Rethinking the advantage of zero-HLA mismatches in unrelated living donor kidney transplantation: implications on kidney paired donation. Transpl Int. 2014; 28(4):401-9. DOI: 10.1111/tri.12495. View

Hou S . Expanding the kidney donor pool: ethical and medical considerations. Kidney Int. 2000; 58(4):1820-36. DOI: 10.1046/j.1523-1755.2000.00345.x. View

Orandi B, Garonzik-Wang J, Massie A, Zachary A, Montgomery J, Van Arendonk K . Quantifying the risk of incompatible kidney transplantation: a multicenter study. Am J Transplant. 2014; 14(7):1573-80. DOI: 10.1111/ajt.12786. View

Meier-Kriesche H, Port F, Ojo A, Rudich S, Hanson J, Cibrik D . Effect of waiting time on renal transplant outcome. Kidney Int. 2000; 58(3):1311-7. DOI: 10.1046/j.1523-1755.2000.00287.x. View

Basu A, Prieto M, Kosberg C, Mai M, Khamash H, Jadlowiec C . Ten Years of Kidney Paired Donation at Mayo Clinic: The Benefits of Incorporating ABO/HLA Compatible Pairs. Transplantation. 2019; 104(6):1229-1238. PMC: 7359217. DOI: 10.1097/TP.0000000000002947. View

10.

Leeaphorn N, Pena J, Thamcharoen N, Khankin E, Pavlakis M, Cardarelli F . HLA-DQ Mismatching and Kidney Transplant Outcomes. Clin J Am Soc Nephrol. 2018; 13(5):763-771. PMC: 5968890. DOI: 10.2215/CJN.10860917. View

11.

Gentry S, Segev D, Simmerling M, Montgomery R . Expanding kidney paired donation through participation by compatible pairs. Am J Transplant. 2007; 7(10):2361-70. DOI: 10.1111/j.1600-6143.2007.01935.x. View

12.

Opelz G . Impact of HLA compatibility on survival of kidney transplants from unrelated live donors. Transplantation. 1997; 64(10):1473-5. DOI: 10.1097/00007890-199711270-00017. View

13.

Simforoosh N, Shemshaki H, Nadjafi-Semnani M, Sotoudeh M . Living related and living unrelated kidney transplantations: A systematic review and meta-analysis. World J Transplant. 2017; 7(2):152-160. PMC: 5409915. DOI: 10.5500/wjt.v7.i2.152. View

14.

Davis C, Delmonico F . Living-donor kidney transplantation: a review of the current practices for the live donor. J Am Soc Nephrol. 2005; 16(7):2098-110. DOI: 10.1681/ASN.2004100824. View

15.

Williams R, Opelz G, McGarvey C, Weil E, Chakkera H . The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors. Transplantation. 2016; 100(5):1094-102. PMC: 8086563. DOI: 10.1097/TP.0000000000001115. View

16.

Tafulo S, Malheiro J, Dias L, Lobato L, Ramalhete L, Martinho A . Improving HLA matching in living donor kidney transplantation using kidney paired exchange program. Transpl Immunol. 2020; 62:101317. DOI: 10.1016/j.trim.2020.101317. View

17.

Opelz G, Dohler B, Middleton D, Susal C . HLA Matching in Pediatric Kidney Transplantation: HLA Poorly Matched Living Donor Transplants Versus HLA Well-Matched Deceased Donor Transplants. Transplantation. 2017; 101(11):2789-2792. DOI: 10.1097/TP.0000000000001811. View

18.

Marlais M, Hudson A, Pankhurst L, Fuggle S, Marks S . Living Donation Has a Greater Impact on Renal Allograft Survival Than HLA Matching in Pediatric Renal Transplant Recipients. Transplantation. 2016; 100(12):2717-2722. DOI: 10.1097/TP.0000000000001159. View

19.

Gjertson D, Cecka J . Living unrelated donor kidney transplantation. Kidney Int. 2000; 58(2):491-9. DOI: 10.1046/j.1523-1755.2000.00195.x. View

20.

Lim W, Chadban S, Clayton P, Budgeon C, Murray K, Campbell S . Human leukocyte antigen mismatches associated with increased risk of rejection, graft failure, and death independent of initial immunosuppression in renal transplant recipients. Clin Transplant. 2012; 26(4):E428-37. DOI: 10.1111/j.1399-0012.2012.01654.x. View