Understanding and using AlloSure donor derived cell-free DNA

Abstract

Renal transplant is a lifesaving and cost-effective intervention for patients with End Stage Renal Failure. Yet it is often regarded as replacement therapy rather than a cure given the overall failure rate over time. With a shortage of organs, this global issue has been further compounded by increased incidences of obesity, hypertension and diabetes, such that the disease burden and need for transplantation continues to increase. Considering the lifetime of immunosupression in transplant patients, there will also be significant associated co-morbidities By leveraging the advances in innovation in Next Generation Sequencing, the field of transplant can now monitor patients with an optimized surveillance schedule, and change the care paradigm in the post-transplant landscape. Notably, low grade inflammation is an independent risk for mortality across different disease states. In transplantation, sub-clinical inflammation enhances acute and chronic rejection, as well as accelerates pathologies that leads to graft loss. Cell free DNA has been shown to be increased in inflammatory processes as we all as provide an independent predictor of all-cause mortality. This review considers the utility of AlloSure, a donor derived cell free DNA molecular surveillance tool, which has shown new clinical insights on how best to manage renal transplant patients, and how to improve patient outcomes.

Keywords: Donor derived cell free DNA; Kidney transplant; Subclinical inflammation.

Fig. 1

Showing the time course post-transplant of inflammation, function, and contributors of injury leading to graft failure. The progression of inflammation and injury can be quantified by AlloSure dd-cfDNA

Fig. 2

Violin plot, showing the continuum of AlloSure across the population. The negatively skewed distribution shows how the change in AlloSure in combination with the absolute number supports clinical decisions at different levels