Real-World Data of Tacrolimus Drug Levels in Ultra-long Kidney Transplant Survivors

Background: Maintaining tacrolimus trough drug levels of more than 5ng/ml decreases the risk of de novo donor-specific antibodies. However, for ultra-long kidney transplant survivors, the evidence of appropriate tacrolimus levels is rare. Therefore, we investigated real-world data on tacrolimus drug levels of ultra-long kidney transplant survivors in a high-volume medical center. Methods: Our center started kidney transplantation in 1990. Among 1375 patients who received kidney transplants in our center from 1990 to 2002, 606 kidney allografts survived more than 20 years. We identified 155 kidney transplant recipients who administered tacrolimus continuously from 15 to 20 years after kidney transplantation and analyzed tacrolimus drug levels and clinical outcomes. Results: The mean tacrolimus trough drug levels between 15 and 20 years after kidney transplantation was 3.94 ng/mL ± 1.52 (range 1.13 – 7.70, median 3.61). After 20 years of kidney transplantation, 11 cases of rejection and 19 cases of graft failure occurred. When analyzing three groups according to the tacrolimus drug levels (<3ng/ml, 3-5ng/ml, >5ng/ml), there were no significant differences in the incidence of rejection (10.2% in <3ng/ml group, 7.4% in 3-5ng/ml group and 2.6% in >5ng/ml group, P = 0.392) and graft failure (16.4% in <3ng/ml group, 11.8% in 3-5ng/ml group and 7.9% in <5ng/ml group, P = 0.486). However, the >5ng/ml group showed the lowest rejection and graft failure incidence without statistical significance. When analyzing two groups according to the tacrolimus drug levels (<5ng/ml group and ≥5ng/ml group), there were also no significant differences in rejection and graft failure. Conclusion: Very low and high tacrolimus drug levels did not show different graft outcomes in ultra-long kidney transplant survivors. However, it seems that tacrolimus drug levels >5ng/ml are not related to poor outcomes compared to physicians’ worries about calcineurin inhibitor toxicities. Well-designed, randomized prospective studies are necessary for more appropriate use of tacrolimus in ultra-long kidney transplant survivors.