Long‐term effects of average calcineurin inhibitor trough levels (over time) on renal function in a prospectively followed cohort of 150 kidney transplant recipients

Abstract

Abstract More favorable clinical outcomes with medium‐term follow‐up have been reported among kidney transplant recipients receiving maintenance therapy consisting of “reduced‐tacrolimus (TAC) dosing,” mycophenolate mofetil (MMF), and low‐dose corticosteroids. However, it is not clear whether long‐term maintenance therapy with reduced‐calcineurin inhibitor (CNI) dosing still leads to reduced renal function. A prospectively followed cohort of 150 kidney transplant recipients randomized to receive TAC/sirolimus (SRL) versus TAC/MMF versus cyclosporine microemulsion (CSA)/SRL, plus low‐dose maintenance corticosteroids, now has 20 years of post‐transplant follow‐up. Average CNI trough levels over time among patients who were still alive with functioning grafts at 60, 120, and 180 months post‐transplant were determined and ranked from smallest‐to‐largest for both TAC and CSA. Stepwise linear regression was used to determine whether these ranked average trough levels were associated with the patient's estimated glomerular filtration rate (eGFR) at those times, particularly after controlling for other significant multivariable predictors. Experiencing biopsy‐proven acute rejection (BPAR) and older donor age were the two most significant multivariable predictors of poorer eGFR at 60, 120, and 180 months post‐transplant (p 0.70). Long‐term maintenance therapy with reduced‐CNI dosing does not appear to cause reduced renal function.