Circadian rhythms in solid organ transplantation

Abstract

Circadian rhythms are daily cycles in physiology that can affect medical interventions. This review considers how these rhythms may relate to solid organ transplantation. It begins by summarizing the mechanism for circadian rhythm generation known as the molecular clock, and basic research connecting the clock to biological activities germane to organ acceptance. Next follows a review of clinical evidence relating time of day to adverse transplantation outcomes. The concluding section discusses knowledge gaps and practical areas where applying circadian biology might improve transplantation success.

Keywords: chronophamacology; circadian rhythms; immunity; ischemia; molecular clock; time of day; transplantation.

Figure. 1:. The circadian system in mammals.

Panel A depicts the “oscillator” paradigm of circadian rhythm generation, in which environmental cues set the phase of an intrinsic and continuously running clock. The clock then imparts a daily structure to biological function, from behavior to biomolecules. Panel B is a schematic of the circadian clock mechanism, composed of transcription factors called “clock genes” that regulate their expression in a feedback loop that takes 24 hours to reinitialize. Panel C depicts the two circadian clock compartments at issue during transplant. The recipient’s circadian system (black) consists of the central CNS pacemaker and peripheral clocks in recipient tissues. Clocks in the donor organ (red), may be set to a different circadian clock time (out of phase) than the recipient clocks at the time of transplantation and lack autonomic innervation that helps to synchronize peripheral clocks.