Very early acute rejection in an Australian and New Zealand kidney transplant population

Abstract

Background:Acute rejection is an important complication of kidney transplantation. Very early acute rejection (VEAR) is defined in this project as rejection during the first week post-transplant. This may have implications for transplant outcomes independent of those attributed to acute rejection (rejection within three months of transplantation). The worldwide trend observed since the end of the 20 th century in which graft survival rates have stagnated despite continued amelioration of acute rejection may be in part explained by VEAR. Aims:The aims of this project are: 1. To document the demographics of an Australian and New Zealand population receiving a kidney-alone transplant between 2004 and 2014 in terms of donor, recipient, and transplant process factors 2. To describe the epidemiology of acute rejection in this cohort 3. To describe characteristics of VEAR 4. To identify potential predictors of VEAR 5. To study the associations between VEAR and patient and graft survivals 6. To relate findings of the above to discordant trends between graft rejection and survival rates Materials and methods:This registry-based, retrospective observational cohort study included all adult recipients of kidneyalone grafts transplanted between 1 January 2004 and 31 December 2014 in Australia and New ii Zealand. VEAR was the primary outcome. Patient death, overall graft loss, and death-censored graft loss (DCGL) were secondary outcomes. Results:8405 kidney grafts were transplanted into 8260 recipients and followed for a median of 4.2 years.Many changes in practice occurred over the study period. Increasingly poorer quality donors were utilised as evidenced by a cohort that was progressively older (mean age 45.1±15.4 years in 2004 v 48.2±16.3 years in 2014; P<0.001), more likely to be affected by hypertension (18 v 21%; P<0.001), and with a higher kidney donor risk index for deceased donors (median 1.20 [0.87-1.53] v 1.29 [1.03-1.66]; P<0.01). Recipients were medically and immunologically more challenging with an increase in mean age (47±12.6 years in 2004 v 51±13.5 years in 2014; P<0.001), a greater burden of comorbidities, and a higher number of human leucocyte antigen (HLA) mismatches (proportion of grafts with five or six mismatches 29% v 37%; P<0.001). The overall rejection rate decreased from 30% in 2004 to 19% in 2014 (P<0.001) with a corresponding fall in VEAR from 8 to 6% (P<0.001). In contrast, there was no significant change in death-censored graft survival (DCGS) for either living (one-year survival 98.2 v 99.1%; P=0.80) or deceased (one-year survival 96.6 v 98.5%; P=0.56) donor grafts. Further investigation of the relationship between VEAR and the discordant rejection-survival paradigm was restricted due to limited information available in the registries. VEAR occurred in 183 of 3025 living donor grafts (6%) and 353 of 5380 deceased donor grafts (7%).Grafts complicated by VEAR were more likely than those without to be a repeat transplant, to have a higher or broader range of peak panel reactive antibody (PRA) and ...