As early as 1980, studies have documented that the quality of organs from deceased donors in kidney transplantation represents one of the crucial factors affecting graft survival (15). Subsequently, there have been numerous research papers evaluating various potential donor risk factors for graft loss in transplantation highlighting the importance of the organ characteristics independent of the transplant recipient. Studies have addressed donor disease history, anatomical characteristics of transplanted organs, donor and recipient matching and donor demographic characteristics (3). The ECD designation has served major importance to the transplant community by labeling those deceased donor kidneys with a high relative risk for graft loss, as well as shortening waiting times for patients consented to receive these organs. Perhaps even more important, the ECD policy was considered to lower discard rates of those organs with a perceived higher risk of graft loss (2). The ECD label included those organs which had an associated relative risk greater than 1.7 from the model generated by the Scientific Transplant Registry for the outcome of overall graft loss (2). This model incorporated donor age, donor history of hypertension, donor serum creatinine and donor cause of death (in particular cerebrovascular death), but did not include a histologic indicator of the structural integrity of the ECD kidney. However, following the pioneeristic experience with emergency autopsies of senile donor kidneys reported by Ende and Zukoski more than 40 years ago (16), several studies evaluated the reasonable concept that preimplantation biopsy of kidneys from older or ECD potential donors can help identify usable kidneys (6). Preliminary uncontrolled studies suggested that kidneys from donors more than 60 but less than 75 years old could be considered for a single transplant if the average rate of glomerulosclerosis is less than 15%, or for a dual transplant if it is more than 15% but less than 50% (17). By this approach, 1-year graft survival ranged from 90% to 95% in recipients of single or dual transplants, respectively. In another series of 26 patients, kidneys were selected and allocated to single or dual transplant on the basis of a scoring system including donor age, serum creatinine, kidney weight and degree of glomerulosclerosis. For each considered parameter, the score was 0 or 1 according to values below or above a predefined cut-off level (65 years for age, 1.8 mg/dL for serum creatinine, 30% for the degree of glomerulosclerosis and 300 g for the weight of both kidneys). A sum of 1 or less resulted in a single kidney transplantation, a sum of 2 in a dual kidney transplantation and a sum of more than 2 in refusal of the organ. At 1 year, single as compared to dual transplant recipients had a similar graft survival (92%), but a worst graft function (18).
Unfortunately, the above studies applied different criteria for selection and allocation of ECD kidneys on the basis of the histology changes, which made interpretation of outcome data difficult and controversial. Some studies considered only, or mainly, the severity of the glomerular changes (17,18), others identified the vascular pathology as the strongest predictor of recipient graft function (19). Moreover, some studies found that renal pathology findings predict graft outcome regardless of donor kidney function (20), while others found that ECD designate provides a description of kidney quality that may obviate biopsy (7). Even more important, the consistency of the histology findings was most likely affected by the different modalities adopted for tissue sampling. To this respect, frozen as compared to permanent sections may save time, but have limitations (20), while needle core biopsy, as opposed to wedge biopsy, may have advantages (21). Indeed, the full cortical thickness, including arteries near the corticomedullary junction, can be sampled by needle core biopsies (Figure 1). By contrast, wedge biopsies often lack these vessels and frequently yield samples in which the superficial cortex is overrepresented. This may result in an overestimate of the overall histology score since, in older people, glomerular and tubulointerstitial scarring tend to localize in the superficial cortex. Thus, histologic evaluations on core biopsies should markedly reduce variability in prognosticating outcomes for recipients of ECD kidneys (21). By this technique (Figure 1), the average number of glomeruli retrieved from each kidney may range from 40 (22) to 80 (23), a sample that is considered more than adequate for a definite histologic diagnosis (20). Notwithstanding, histology score and subsequent graft outcomes are independent of the number of glomeruli retrieved with the biopsy sampling (Perico N., Bergamo, June 2006, personal communication).