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 early conversion from a 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 for ten subjects; BOLD for eight subjects. The diffusion coefficient ADCD decreased in the CsA-treated group over time, whereas it increased in the EVE group (p = 0.046, medulla). The change in ADCD from months 4.5 to 12 significantly differed between groups in the 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 EVE-treated groups over time. Similarly, R2* values at month 12 were higher in the CsA-treated group compared to the 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.

Diffusion-Weighted Magnetic Resonance Imaging: Clinical Potential and Applications

“…Diffusion MRI, reflecting acute changes in the renal microstructure even before alterations in laboratory parameters, could become part of a multi-modality-based clinical protocol alongside clinical information, routine renal parameters, and advanced urinary injury markers and may help facilitate the appropriate therapy in at-risk patients. Mani and colleagues [ 53 ] used DWI combined with blood-oxygen-level-dependent (BOLD) MRI to non-invasively assess differences in kidney graft diffusion, perfusion, and oxygenation over time between kidney transplant recipients treated with ciclosporin or everolimus. Despite negative preliminary findings due to the limited sample size, the study findings showed an improvement in graft diffusivity over time and a tendency for ameliorated tissue oxygenation after the switch to everolimus, suggesting an impact of the immunosuppressive regimen on fMRI parameters of the kidney graft.…”