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

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 < 000001 and 0.000003 for older donor age at 60 and 120 months; p = 0.00008 and <0.000001 for previous BPAR at 60 and 120 months). Assignment to CSA also implied a significantly poorer eGFR (but with less magnitudes of effect) in multivariable analysis at 60 and 120 months (p = 0.01 and 0.002). Higher ranked average CNI trough levels had no association with eGFR at any timepoint in either univariable or multivariable analysis (p > 0.70). Long‐term maintenance therapy with reduced‐CNI dosing does not appear to cause reduced renal function.