Donor liquid biopsy and outcomes in kidney transplantation

Kidney transplantation is the treatment of choice for patients with kidney failure. Priority on the waiting list and optimal donor-recipient matching are guided by mathematical scores, clinical variables and macroscopic observation of the donated organ. Despite the increasing rates of successful kidney transplantation, maximizing the number of available organs while ensuring the optimum long-term performance of the transplanted kidney remains both key and challenging, and no unequivocal markers are available for clinical decision making. Moreover, the majority of studies performed thus far has focused on the risk of primary non-function and delayed graft function and subsequent survival and have mainly analysed recipients' samples. Given the increasing use of donors with expanded criteria and/or cardiac death, predicting whether grafts will provide sufficient kidney function is increasingly more challenging. Here we compile the available tools for pre-transplant kidney evaluation and summarize the latest molecular data from donors that may predict short-term (immediate or delayed graft function), medium-term (6 months) and long-term (≥12 months) kidney function. The use of liquid biopsy (urine, serum, plasma) to overcome the limitations of the pre-transplant histological evaluation is proposed. Novel molecules and approaches such as the use of urinary extracellular vesicles are also reviewed and discussed, along with directions for future research.