Background: Under the safety-net policy, liver transplant candidates with kidney dysfunction, when offered organs from donor with a positive crossmatch (+XM), now have the option of either simultaneous liver-kidney transplantation (SLKT) or Kidney after liver transplant. The aim of this study was to assess the effect of +XM on outcomes of SLKT during the safety net policy era.  
Methods: Using the United Network for Organ Sharing database 2,832 adult SLKT recipients between August 2017 to September 2023, were divided into in two groups, +XM (N=497) and negative crossmatch (–XM) (N=2335). Post-transplant outcomes in these cohorts were analyzed using Kaplan-Meier and Cox proportional hazard models. As a subgroup analysis, liver transplant alone and SLKT were also analyzed in +XM and –XM groups.
Results: Compared with -XM, SLKT recipients with +XM had a lower percentage of males (27% vs 64%, P<0.001), fewer alcohol-related liver disease (29% vs 40%), more metabolic dysfunction-associated steatohepatitis (40% vs 29%), and a higher median model for end-stage liver disease (MELD) score (30 vs 29, P=0.018).
 
In +XM group, cold ischemia time was shorter for both donor liver (5.6 hours vs 6.0 hours, P=0.020) and donor kidney  (12 hours vs 12 hours, P=0.18). Depletional induction was used more in the +XM group (21% vs 12%, P<0.001). Post-transplant length of hospital stay was longer in the +XM group (15 days vs 13 days, P=0.016). The rate of delayed kidney-graft function was the same between the two groups (27% vs 28%, P=0.85). Serum creatinine was lower in +XM group at discharge (1.13 mg/dl vs 1.30mg/dl, P<0.001), at 6 months (1.12 mg/dl vs 1.23 mg/dl, P<0.001), and at one year (1.19 mg/dl vs 1.25 mg/dl, P<0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between +XM and –XM.
 
Among +XM, one-year patient survival and liver survival were better in SLKT than those in liver transplant alone. +XM was not associated with kidney graft survival (hazard ratio 1.07; 95% Confidence Interval 0.82-1.39, P=0.63), and in +XM cohort, liver transplant alone was associated with mortality and graft failure compared to SLKT (hazard ratio 2.88; 95% Confidence Interval 1.19-6.92, P=0.018).
Conclusions: Crossmatch positivity in a selected group of SLKT recipients was not associated with worse patient or graft outcomes and may not influence the decision to use these organs.