Kidney Week

Abstract: FR-PO1023

Cumulative Tacrolimus Variability and Long-Term Survival in Kidney Transplant Recipients

Session Information

• Transplantation: Clinical - Pharmacology and Nonkidney Solid Organ Transplants
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2102 Transplantation: Clinical

Authors

• Yuan, Zhongyu, University of Wisconsin-Madison Department of Population Health Sciences, Madison, Wisconsin, United States

Zhongyu Yuan, MBBS

• Parajuli, Sandesh, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States

Sandesh Parajuli, MBBS

• Jorgenson, Margaret R., UW Health, Madison, Wisconsin, United States

Margaret R. Jorgenson, PharmD

• Mandelbrot, Didier A., Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States

Didier A. Mandelbrot, MD

• Astor, Brad C., University of Wisconsin-Madison Department of Population Health Sciences, Madison, Wisconsin, United States

Brad C. Astor, PhD, MPH

Background

Intra-patient variability (IPV) has been proposed as a tool for tacrolimus (Tac) monitoring, considering its association with early outcomes after transplantation. There is scant evidence of the impact of cumulative Tac IPV beyond the first year on long-term survival in kidney transplant recipients (KTR).

Methods

We analyzed data from KTRs at our center during 2010-2019, who survived at least 1 year after transplant and received Tac and mycophenolate mofetil (with or without steroid). Annual Tac IPV beyond the 1^st year was measured by the coefficient of variation (CV) using outpatient measurements of C₀ levels. Weighted cumulative exposure models were fitted to assess the association of cumulative Tac IPV with outcomes (i.e., uncensored graft failure, death-censored graft failure (DCGF), and patient mortality). Models were adjusted for donor and recipient characteristics, events in the 1^st year (e.g., delayed graft function, rejection, cytomegalovirus, BK polyomavirus, fungal infection), and estimated glomerular filtration rate in the 1^st quarter of the 2^nd year.

Results

A total of 1996 KTRs were followed over a median of 6.6-years. One-third (33%) had a Tac CV ≥ 30% in the 2^nd year post-transplant, which decreased in the 3^rd year and maintained stable thereafter. Significant associations were observed between Tac IPV and long-term survival. The strength of associations attenuated over time, especially beyond 5 years (Figure 1). Every 10% higher CV in the past 5 years was associated with a 71% higher risk (adjusted hazard ratio [aHR]=1.71, 95%CI, 1.58-1.84) of uncensored graft failure and a 61% higher risk (aHR=1.61, 95%CI, 1.42-1.81) of patient mortality. KTRs with a CV of 30% in the past 5 years would have a 3.57-fold higher risk of DCGF compared with a CV of 10% (Table 1).

Conclusion

High cumulative Tac IPV is associated with inferior graft and patient survival. Further study is needed to determine effective strategies to reduce Tac IPV.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025z7rsxgec