Transition of Renal Patients Using AlloSure Into Community Kidney Care (TRACK): Protocol for Long-Term Allograft Surveillance in Renal Transplant Recipients (Preprint)

Abstract

BACKGROUND End Stage Kidney Disease (ESKD) patients require complex and expensive medical management. Kidney transplantation remains the treatment of choice for ESKD and is considered superior to all other modalities of renal replacement therapy (RRT) or dialysis. However, access to kidney transplant is limited by critical supply-demand making it extremely important to ensure longevity of transplanted kidneys. This is prevented through life-long immunosuppression, with caution not to overly suppress the immune system, resulting in toxicity and harm. Transition of care to community nephrologists after initial kidney transplantation and monitoring at a transplant center is an important process to ensure delivery of effective and patient-centric care closer to home. Once transplanted, laborious surveillance of the immune system and monitoring for potential rejection and injury is undertaken through an armamentarium of screening modalities. Post-transplant surveillance for kidney function and injury remained key to follow up care. While kidney function, quantified by estimated glomerular filtration rate (eGFR) and serum creatinine (SCr), and kidney injury, measured by proteinuria and hematuria, are standard biomarkers used to monitor injury and rejection post-transplant, they have recently been demonstrated to be inferior in performance to that of AlloSure® (CareDx, Inc. Brisbane, CA), circulating donor-derived cell-free DNA (dd-cfDNA). OBJECTIVE The outcomes and methods of monitoring renal transplant recipients (RTR) post-transplant have remained stagnant over the past 15 years. The aim of this study is to consider intensive surveillance using AlloSure® dd-cfDNA in an actively managed protocol assessing whether it increases long-term allograft survival in kidney transplant recipients compared with current standard clinical care in community nephrology. METHODS The study protocol will acquire data from a phase IV observational trial to assess a cohort of 2500 RTR patients managed using AlloSure® dd-cfDNA and patient care managers versus 1000 propensity matched historic controls using UNOS SRTR data. Data will be managed in a centralized electronic data server. RESULTS The primary outcome will be superior allograft survival, as a composite of return to dialysis, re-transplant, death due to allograft failure and death with a functional graft DWFG (infection, malignancy, and cardiovascular death). The secondary endpoints will assess improved kidney function through decline in eGFR and immune activity through development of donor specific antibody (DSA). CONCLUSIONS Based on a significant literature base, we believe implementing the surveillance of dd-cfDNA in the kidney transplant population will have a positive impact on graft survival. Through early identification of rejection and facilitating timely intervention, prolongation of allograft survival versus those not managed by dd-cfDNA surveillance protocol should be superior.