Influence of immunosuppressive regimen on diffusivity and oxygenation of kidney transplants – analysis of functional MRI data from the randomized ZEUS trial

Abstract

The ZEUS study was a multi-center randomized controlled trial investigating the effect of an early conversion from ciclosporin-based to an everolimus-based regimen on graft function twelve months post-transplantation. In this investigator-initiated sub-study, functional magnetic resonance imaging (fMRI) of kidney grafts was prospectively performed to non-invasively assess differences in graft oxygenation, diffusion and perfusion between groups and time-points using diffusion-weighted imaging (DWI) and blood oxygen level-dependent (BOLD)-MRI. Sixteen patients underwent DWI and BOLD-MRI at months 4.5 and 12 post-transplantation on a 3 Tesla and 1.5 Tesla (n=3) MR scanner. After exclusion due to image quality, outlier values or missing data, DWI was analyzed in ten, BOLD in eight subjects. The diffusion coefficient ADCD decreased in the CsA-group over time, whereas it increased in the EVE-group (p=0.046, medulla). The change in ADCD from month 4.5 to 12 significantly differed between groups in cortex (p=0.033) and medulla (p=0.019). In BOLD, cortico-medullary transverse relaxation rate R2* increased (decreased tissue oxygen) in the CsA-treated and decreased in the EVE-treated group over time. Similarly, R2* values at month 12 were higher in the CsA- vs. EVE-treated group. There was no significant difference for the perfusion fraction FP. In conclusion, this prospective sub-study of the ZEUS trial suggests an impact of immunosuppressive regimen on fMRI parameters of the kidney graft.