Does HLA matching matter in the modern era of renal transplantation?

Abstract

Children with end-stage kidney disease should be offered the best chance for future survival which ideally would be a well-matched pre-emptive kidney transplant. Paediatric and adult practice varies around the world depending on geography, transplant allocation schemes and different emphases on living (versus deceased) donor renal transplantation. Internationally, paediatric patients often have priority in allocation schemes and younger donors are preferentially allocated to paediatric recipients. HLA matching can be difficult and may result in longer waiting times. Additionally, with improved surgical techniques and modern immunosuppressive regimens, how important is the contribution of HLA matching to graft longevity? In this review, we discuss the relative importance of HLA matching compared with donor quality; and long-term patient outcomes including re-transplantation rates. We share empirical evidence that will be useful for clinicians and families to make decisions about best donor options. We discuss why living donation still provides the best allograft survival outcomes and what to do in the scenario of a highly mismatched living donor.

Keywords: Deceased donors; Human leukocyte antigens; Kidney transplantation; Living donors; Matching; Mismatching.

Fig. 1

Comparison of donor age and HLA MM. Analysis was performed by Foster et al. using USRD [14]. Each curve shows the adjusted estimated graft survival for a white 14-year-old recipient transplanted in 1999–2004 from a DD with a different age and HLA MM combination. Also shown are the adjusted HRs from a model comparing graft survival for each combination compared to the reference 4–6 HLA MM donor of < 35 years of age. For donors < 35 years, 0–1 HLA MM had statistically significant improved allograft survival. Donors > 45 years had worse allograft survival though in the well-matched (0–1 MM) group, graft survival outcomes were similar. Therefore, both allograft quality and HLA matching are important for determining survival outcomes though there is a larger effect of donor quality in the earlier post-transplant years (5–10 years)

Fig. 2

KM analysis of CTS data by Opelz et al. [17]. Poorly matched (4–6 MM) LD had worse allograft survival compared with a very well-matched (0–1 MM) DD. Likewise, transplants from a 1–3 MM LD had similar outcomes to the very well-matched (0–1 MM) DD group. These results and data from other studies support entering high HLA MM (4–6 MM) LD into kidney paired exchange schemes