High intraindividual tacrolimus variability (IPVTac) is associated with premature graft loss in larger adult populations. However, the importance of this parameter for the development of de novo donor-specific HLA antibodies (dnDSA) has not been sufficiently investigated yet. Therefore, the aim of this study was to determine the role of IPVTac in the period 6 to 12 months after transplantation (RTx) for subsequent development of dnDSA (> one year after transplantation).

Material and methods:

The inclusion criteria were: (i) absence of HLA-DSA before RTx, (ii) HLA-DSA measurements at least once a year post-transplant, (iii) at least three tacrolimus trough level measurements. The IPVTac was calculated on the basis of the coefficient of variability (= standard deviation/mean*100). HLA-DSA with a MFI > 500 (Luminex-SAB; One Lambda) were considered positive.

Results:

A total of 900 tacrolimus trough levels from 54 patients were analyzed (median measurements per patient 14.5; IQR 9.0-22.0). The median tacrolimus variability was 28% (IQR 22.0%-41.5%). The upper IPVTac quartile was defined as the cut-off value for high IPVTac. Based on this, Kaplan-Meier analysis showed a significantly increased risk for the development of dnDSA more than 12 months post-RTx in the high IPVTac group (p = 0.02). In this low immunological risk cohort, no association of IPVTac with late rejections (> 1 year after RTx) or accelerated loss of graft function (eGFR < 50% compared to baseline) within 5 years post-RTx could be observed.

Conclusions:

A high IPVTac is associated with an increased risk of subsequent dnDSA-development. Therefore, an intensified long-term immunological monitoring should be considered in patients with a high IPVTac in the period from 6 to 12 months post-RTx.