*Purpose: Kidney transplant (KT) recipients with failed allografts constitute nearly 12% of the current waitlist in the US. Sensitization as a result of graft failure (GF) leads to longer wait-times and lower repeat KT rates. In addition, repeat KT in the setting of preexisting DSA may contribute to worse outcomes. This study explored factors affecting sensitization following GF.

*Methods: Inclusion criteria included 1) index KT between 7/2009 and 6/2019, 2) GF between 1/2016 and 6/2020, and 3) repeat transplant evaluation including cPRA analysis after GF. The most recent available cPRA value was used for analysis. Among those with pre-index KT cPRA of ≤ 50, analyses were done to identify risk factors for 1) increase in cPRA (delta cPRA) of ≥ 50-points, and 2) sensitization to cPRA of ≥ 98.

*Results: 55 KTs, 14% of which were simultaneous pancreas kidney transplants, met our inclusion criteria. Median (range) pre-index KT cPRA was 0 (0-100), post-GF cPRA was 85 (0-100), and time from GF to most recent cPRA was 14.5 months (1.5-50.8). Most patients were on triple immunosuppression prior to GF. Steroids were continued in 85%, calcineurin inhibitor (CNI) in 58%, and antimetabolite in 31%. Among 45 KTs with pre-transplant cPRA ≤ 50, univariate analysis showed that those with delta cPRA ≥ 50 were less likely to be SPK recipients (4% vs 32%, p=0.02), and less likely to have been continued on steroid (65% vs 100%, p=0.004), CNI ( 30% vs 86%, p<0.001), or antimetabolite after GF (17% vs 50%, p=0.03). There was no difference in age, sex, race, blood type, ESKD etiology, HLA mismatches, induction or maintenance immunosuppression, time from transplant to GF or nephrectomy rates between the two groups. Ongoing CNI use after GF was protective against delta cPRA ≥ 50 (Odds ratio (OR) 0.12, p=0.02), and benefit associated with ongoing steroid approached statistical significance (OR 0.13, p=0.07). Using delta cPRA as a continuous variable, linear regression modeling yielded similar results for ongoing CNI use (p=0.003) and ongoing steroid use (p=0.03). In another analysis evaluating sensitization to cPRA ≥ 98, ongoing CNI use was the only protective variable (OR 0.07, p=0.009).

*Conclusions: Continuing CNI and steroids are associated with significantly lower risk of sensitization after kidney allograft failure. CNIs appear to be particularly important in preventing sensitization to cPRA ≥ 98.

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