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Incidence and impact of rejection following simultaneous liver-kidney transplantation. BACKGROUND & AIMS: Due to hepatic immunoregulation, simultaneous liver-kidney recipients are presumed to be reasonably protected from kidney rejection and typically receive less immunosuppression compared to kidney transplants alone. However, data to support these conclusions and practices are sparse. METHODS: We characterized the incidence and types of rejection, graft function, and graft and patient survival in a large population of simultaneous liver-kidney recipients (n=140) with long-term follow-up at our centre (1998-2010). RESULTS: Acute cellular, antibody-mediated, and chronic kidney rejection was diagnosed in 9 (6.4%), 2 (1.4%), and 1 (0.7%) patient, respectively. Borderline acute kidney rejection was diagnosed in another 16 patients (11.4%). Acute cellular liver rejection occurred in 16 (11.4%) and chronic liver rejection in 4 (2.9%). One-, three-, and five-year patient survival was 86.4%, 78.0%, and 74.0%, respectively, and did not significantly differ by presence or absence of kidney or liver rejection. However, kidney rejection was associated with decreased renal function by lower serum GFR over time (p=0.003). CONCLUSIONS: Various forms of kidney rejection occurred in ∼20% of our simultaneous liver-kidney recipients and were associated with deterioration in graft function, indicating that the liver may not confer complete protective allo-immunity. More stringent graft monitoring and management strategies, perhaps more akin to kidney transplant alone, should be prospectively studied in simultaneous liver-kidney recipients.