The potential role of antimetabolite in preventing allosensitization before kidney retransplantation

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Background and aims Retransplantation is becoming more common. Allosensitization represents an increasing issue, as it prolongs the time on the waiting list and worsens the outcome of a second transplant. The optimal maintenance immunosuppression (IS) after graft failure remains unclear. Methods This is a retrospective single-center study including kidney retransplant recipients (KRTRs) who underwent a retransplantation in the University Hospital of Zurich between 2012 and 2023. We analyzed which factors and especially which kind of maintenance IS after graft failure could affect allosensitization. Results In our cohort, 191/1,040 (16%) were retransplantations. Of the included KRTRs, 27/129 (20%) were living donations (LDs). The median waiting time for deceased donations (DDs) was 4 years. The burden of IS decreased from graft failure to retransplantation (triple IS 54 vs. 12%, p < 0.05), while the allosensitization increased [number of HLA-antibodies (Ab) MFI > 1,000/patient 5.8 vs. 12.45, p > 0.001]. In the univariate analysis transplant, nephrectomy was associated with a higher calculated panel reactive Ab (cPRA): 90 vs. 29 ( p < 0.0001). At retransplantation, intake of calcineurin inhibitor (CNI) was associated with lower cPRA (27% vs. 78% no CNI, p < 0.001), as was intake of antimetabolite [23% for azathioprine, 20% for mycophenolic acid (MPA), and 88% for no antimetabolite, p < 0.001] and of prednisone (PDN) (24% vs. 66% no PDN, p = 0.02). First retransplantation was also associated with a lower cPRA when compared to a second or a third retransplantation (41% vs. 78% vs. 88%, p = 0.02). In the multivariable analysis, only the intake of antimetabolite remained associated with cPRA <85% at retransplantation. Surprisingly, we could find a weak correlation between cPRA and waiting time to retransplantation ( r = 0.25, R 2 = 0.06, p = 0.01). Conclusion The intake of antimetabolite at retransplantation showed a protective effect against allosensitization. Waiting time to retransplantation had only a weak correlation with allosensitization over the whole cPRA spectrum in this Swiss cohort study.

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