Introduction: Incompatible living donor kidney transplantation (ILDKT) offers a survival benefit compared to dialysis for patients with donor specific antibody (DSA) who do not have a compatible living donor. Longer-term outcomes have not been characterized in this population, but must be quantified to inform treatment selection for patients with an incompatible willing donor, and counseling for ILDKT recipients.

Method: We compared 1,406 ILDKT to 17,542 compatible LDKT (CLDKT) recipients using a 25-center cohort from the United States 1997-2016, linked to national registry data (SRTR). Participating centers classified ILDKT recipients as positive Luminex, negative flow crossmatch (PLNF, n=376); positive flow, negative cytotoxic crossmatch (PFNC, n=687); or positive cytotoxic crossmatch (PCC, n=343). We used multivariable Cox regression to quantify the risk of mortality and death-censored graft failure (DCGF), and multilevel mixed-effects linear regression to evaluate eGFR decline (CKD-EPI creatinine equation 2021) in ILDKT and CLDKT recipients.

Results: The cumulative mortality risk for CLDKT, PLNF, PFNC, and PCC was: 1.6%, 1.9%, 3.2%, and 8.2% at one year; 22.5%, 18.4%, 29.4%, and 36.1% at ten years; and 39.1%, 36.1%, 45.4% and 51.6% at fifteen-years (p<0.001) (Figure 1A). Although this translated to an equivalent mortality risk for PLNF recipients (aHR=_0.830.96_1.12, p=0.6) after adjustment, PFNC and PCC recipients had a 1.48-fold (aHR=_1.301.48_1.68, p<0.001) and 1.66-fold (aHR=_1.331.66_2.08, p<0.001) higher risk compared their CLDKT counterparts, respectively. The cumulative risk of DCGF for CLDKT, PLNF, PFNC, and PCC was: 1.9%, 2.1%, 3.4%, and 11.1% at one year; 16.8%, 20.5%, 33.1%, and 41.0% at ten years; and 25.5%, 33.1%, 45.2% and 52.5% at fifteen-years (p<0.001) (Figure 1B). After adjustment, this translated to higher DCGF across all levels of DSA strength (aHR PLNF=_1.141.41_1.73, PFNC=_1.491.71_1.95, PCC=_1.612.08_2.67; p for all≤0.001). Conversely, ILDKT and CLDKT recipients had comparable average eGFR immediately post-transplant (difference=_-4.22-1.51_1.20 mL/min/1.73m², p=0.3). However, ILDKT recipients had faster decline in eGFR per year compared to CLDKT recipients (difference in slope=_-1.06-0.76_-0.47 mL/min/1.73m² per year, p<0.001; decline over 5 years for ILDKT=_-9.01-7.55_-6.10 mL/min/1.73m² vs. CLDKT=_-4.19-3.74_-3.29 mL/min/1.73m²).

Conclusion: Patient and graft survival following ILDKT is good through fifteen years post-transplant, supporting this modality, but survival is worse compared to CLDKT recipients. ILDKT recipients bear close monitoring to maximize graft life.