With a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal kidney offers from older donors should be accepted. Here, we externally validate existing prediction models in a European population of older deceased donors, and subsequently developed and externally validated an adverse outcome prediction tool. Recipients of kidney grafts from deceased donors 50 years of age and older were included from the Netherlands Organ Transplant Registry (NOTR) and United States organ transplant registry from 2006-2018. The predicted adverse outcome was a composite of graft failure, death or chronic kidney disease stage 4 plus within one year after transplantation, modelled using logistic regression. Discrimination and calibration were assessed in internal, temporal and external validation. Seven existing models were validated with the same cohorts. The NOTR development cohort contained 2510 patients and 823 events. The temporal validation within NOTR had 837 patients and the external validation used 31987 patients in the United States organ transplant registry. Discrimination of our full adverse outcome model was moderate in external validation (C-statistic 0.63), though somewhat better than discrimination of the seven existing prediction models (average C-statistic 0.57). The model's calibration was highly accurate. Thus, since existing adverse outcome kidney graft survival models performed poorly in a population of older deceased donors, novel models were developed and externally validated, with maximum achievable performance in a population of older deceased kidney donors. These models could assist transplant clinicians in deciding whether to accept a kidney from an older donor.

Donor organ shortage, growing waiting lists and substantial organ discard rates are key problems in transplantation. The critical importance of organ quality in determining long-term function is becoming increasingly clear. However, organ quality is difficult to predict. The lack of good measures of organ quality is a serious challenge in terms of acceptance and allocation of an organ. The underlying review summarizes currently available methods used to assess donor organ quality such as histopathology, clinical scores and machine perfusion characteristics with special focus on molecular analyses of kidney quality. The majority of studies testing molecular markers of organ quality focused on identifying organs at risk for delayed graft function, yet without prediction of long-term graft outcome. Recently, interest has emerged in looking for molecular markers associated with biological age to predict organ quality. However, molecular gene sets have not entered the clinical routine or impacted discard rates so far. The current review critically discusses the potential reasons why clinically applicable molecular quality assessment using early kidney biopsies might not have been achieved yet. Besides a critical analysis of the inherent limitations of surrogate markers used for organ quality, i.e., delayed graft function, the intrinsic methodological limitations of studies assessing organ quality will be discussed. These comprise the multitude of unpredictable hits as well as lack of markers of nephron mass, functional reserve and regenerative capacity.

Organ shortage represents one of the major limitations to the development of kidney transplantation. To increase the donor pool and to answer the ever increasing kidney request, physicians are recurring to marginal kidneys as kidneys from older donors, from hypertensive or diabetic donors and from non-heart beating donors. These kidneys are known to have frequently a worse outcome in the recipients. To date major problem is to evaluate such kidneys in order to use or to discard them before transplantation. The use of such kidneys create other relevant question as whether to use them as single or dual transplant and to allocate them fairly according transplant programs. The pre-transplant histological evaluation, the clinical evaluation of the donor or both the criteria joined has been used and according the time each criterion prevailed over the others. Aim of this review has been to examine the advantages and the drawbacks of any criterion and how they have changed with time. To date any criterion has several limitations and several authors have argued for the development of new guidelines in the field of the kidney evaluation for transplantation. Several authors argue that the use of omic technologies should improve the organ evaluation and studies are ongoing to evaluate these technologies either in the donor urine or in the biopsies taken before transplantation.

The growing gap between inadequate supply and constantly high demand for kidney transplantation observed in the last two decades led to exploring the possibility of using organs from older donors with an increasing number of comorbidities. The main issue in this scenario is to identify transplantable organs and to allocate them to the most suitable recipients. A great number of clinical investigations proposed several acceptance/allocation criteria to reduce the discard rate of these kidneys and to improve their outcome, including histological features at the time of transplant. Despite the widespread use of several histological scoring systems, there is no consensus on their value in predicting allograft survival and there is established evidence that histological analysis is the most common reason to discard expanded criteria donor kidneys. To overcome this issue, a clinical scoring system, the Kidney Donor Profile Index (KDPI), was developed on the basis of easily accessible donor features. The KDPI score, adopted in the new US allocation procedure, has good reproducibility but presents several limitations, as suggested also in this issue of Clinical Kidney Journal. This observation should stimulate the search for novel scores combining clinical, histological and molecular features in an attempt to improve the decision process.