Randomized clinical trial of a novel donor-derived cfDNA test to detect rejection in CPV-simulated renal transplant patients.Peabody, J., et al.
International Urology & Nephrology 2020 [record in progress]
The aim of this study was to determine whether a novel donor-derived cell-free DNA (dd-cfDNA) test is able to detect rejection earlier and improve diagnostic and thepeutic accuracy in clinical performance and value (CPV)- simulated kidney transplant recipients.
Participants were randomized to either the group with access to dd-cfDNA testing or the group without access dd-cfDNA testing.
175 practicing nephrologists.
The outcomes of interest were improvements in primary diagnosis of clinically apparent rejection, subclinical rejection and/or non-rejection, improved patient outcomes (including appropriate biopsy, referral to transplant center and/or appropriate change of immunosuppressive therapy), and reduction in health-care utilization.
This industry-sponsored study investigates the clinical utility of cfDNA testing in a simulated setting with 175 nephrologists, randomising them to availability of cfDNA levels or not for a series of curated case vignettes. The investigators find that availability of cfDNA results improves clinician’s ability to distinguish rejection from other causes of graft injury, with potential to better target invasive biopsy and guide immunosuppressive management. Whilst this is a novel approach, the key issue here is the selection/creation of the simulated patient cohort. The three patient types are (1) patients with creatinine rise and acute rejection, (2) patients with subclinical rejection and stable creatinine and (3) patients with elevated creatinine and tac toxicity/renal artery stenosis. These are all scenarios in which cfDNA is known to add value, and they have deliberately avoided the more challenging false-positive cases where cfDNA could be elevated in the absence of rejection (e.g. BK nephropathy, ATN, infection). Also, there is no description as to how the cfDNA levels were determined for the simulated patients – one assumes that they use “perfect” test results, whereas in reality the test results are likely to vary and/or be indeterminate in some cases.
ClinicalTrials.gov - NCT03765203