A total of 229 consecutive kidney transplants that met the study criteria were identified during the 11-year period. Median follow-up was 5.1 years (range, 12.1– 132 months) as of December 2008 and all were transplanted more than 1 year before this study. TableI summarizes the transplant recipient demographic characteristics of the 2 groups. There was no difference in age, sex, body mass index (BMI), warm ischemia time (WIT), or cold ischemia time (CIT) in either deceased-donor kidney transplants or live-kidney transplants between the 2 groups. However, African American ethnicity represented an overwhelmingly higher proportion in the MM group, while white ethnicity was the majority of the M group (p < .0001). The peak PRA was significantly higher in the M group than the MM group for deceased-donor kidney transplants. These different distributions become less significant in live donor kidney transplants (TableI).
There were no differences in the graft function as measured by eGFR between the M and MM groups for both deceased-donor and live-kidney transplants (Table II). The 5-year cumulative incidence of biopsy confirmed and clinically treated acute rejection were significantly higher in the MM group than in the M group for both deceased-donor (Figure1A, 27.6% versus 9.6%, p = .003) and live-kidney transplants (Figure1B, 34 .4% versus 3.8%, p = .01). The relative risk (RR) of acute rejection was 2.94 (95% confidence interval [CI]: 1.32–6.23, p = .003) in mismatched deceased-donor kidney transplants, and 9.09 (95% CI: 1.23–64.9, p = .01) in mismatched live-kidney transplants.
The 5-year death-censored graft survival estimated by the Kaplan-Meier method was significantly higher in the M group than in the MM group for deceased-donor kidney transplants (Figure2). The estimated deceased-donor graft survivals at 1, 3, and 5-years were 100%, 89%, and 84% in the M group, and 93%, 79%, and 70% in the MM group (log-rank, p = .018). We further sub-analyzed deceased-donor graft survivals by their peak PRA levels (PRA <20% versus >20%). There was no survival difference between the M and MM groups for PRA levels less than 20% (Figure3A). The estimated graft survival at 1, 3, and 5-years were 100%, 82%, and 78% in the M group, and 94%, 81%, and 69% in the MM group (log-rank, p = .32). However, for sensitized patients with PRA levels greater than 20%, HLA-matched deceased-donor kidney transplants had a superior graft survival compared with mismatched transplants (Figure3B). The estimated graft survival at 1, 3, and 5-years were 100%, 96%, and 90% in the M group, and 88%, 75%, and 75% in the MM group (log-rank, p = .023). For live-kidney transplants, there was no statistical significance in the graft survival between the M and MM groups (Figure4). The estimated living-donor graft survival at 1, 3, and 5-years were 100%, 100%, and 89% in the M group, and 93%, 81%, and 72% in the MM group (log-rank, p = .077). The causes of graft loss are summarized in TableII. DWGF and chronic allograft nephropathy (CAN) were the main causes of graft loss. Acute rejection did not cause any graft loss in the M groups of both deceased-donor and live donor kidneys, but it was an important cause of graft loss in the MM groups, especially in the deceased-donor kidney transplants (p = .035).
The risk factors for graft loss were also examined by Cox's proportional hazard regression analysis and significant risk factors were further analyzed by a stepwise variable selection model. The risk factors included recipient age, sex, race, BMI, PRA, previous transplant, CIT, WIT, and mismatched kidneys. Mismatched kidneys and recipient age were found to be independent risk factors for graft loss in deceased-donor kidney transplants with a hazard ratio (HR) of 2.27 (95% CI: 1.009–5.09, p = .047) and 0.96 (95% CI: 0.093–0.97, p = .0001), respectively. After adjusting for acute rejection, the effect of mismatched kidneys loses statistical significance (HR: 1.84, 95% CI: 0.84–4.21, p = .142) indicating a mediating effect.