This study shows that a pre-implantation kidney biopsy performed during organ procurement, before the aortic cross-clamping significantly reduced mortality and graft loss when compared to ex-situ kidney biopsy.
The Italian allocation policy provides to perform a pre-implantation biopsy to accept or decline ECD kidneys for transplantation and whether to decide if SKT or DKT should be performed.4 In other countries, performing pre-implantation biopsy is still debated and controversial. For example, the United Network of Organ Sharing (UNOS) Kidney Transplantation Committee has recently approved a new allocation policy which is based on the KDPI and not on the histological features.9 Even for this context, where the allocation policy does not include a pre-transplant biopsy performed routinely, some authors suggests that for hight KDPI values (even for KDPI close to 100), a pre-transplant kidney biopsy could be important to support the suitability of the graft and the allocation to SKT or DKT.[20, 21] Donors included in this study had a very high median KDPI (95%) and, despite this, we maintained the survival of the graft and the patient comparable to the transplant performed with donors with standard criteria.
One of the main concerns of allocation systems using pre-implantation kidney biopsy, is that the histological examination is time consuming and may increase CIT. Usually, the biopsy is performed at the end of procurement, on surgical back table. From 2012 we have started to perform kidney biopsies as one of the first procedures during multiorgan procurement, sending them immediately to the pathologist while the recovery is still ongoing. Our hypothesis was that this may have led to an improved outcome due to a decrease of CIT. In our study, the median CIT was lower in transplants with ISKB than those with ESKB. Since the cascade of events leading to kidney injury is initiated by cold ischemia, it is reasonable to think that the longer is the duration of cold ischemia, the higher is its harmful impact  and it is plausible that a prolonged CIT may have a negative impact on graft survival: the injuries consequent to the cold storage can lead to kidney damage and to the activation of the immune response, both of which may affect the outcome after transplantation. In literature, there is no consensus on the precise relationship of CIT with the transplantation outcomes. The injuries consequent to the cold storage can lead to kidney damage and to the activation of the immune response, both of which affect the outcome after transplantation. Debout et al. reported that even short differences in CIT may influence both graft and patient survival. A recent Dutch study reported that a higher CIT is associated with an increased risk of graft failure. Our study confirms these hypotheses, since overall and graft survival was significantly higher in patients with ISKB compared to those with ESKB.
Our study has some limitations. First, performing the ISKB is less useful when kidney biopsies are not performed routinely to allocate grafts. In certain contexts, furthermore, this method is not applicable because of a different organization and the time required for the pathological examination. In our Region, the allocation of the biopsy involves a complex organization as all biopsies are centralized in our center and the availability of experienced pathologist 24 hours a day is necessary. This does not change our standard of practice where the same specialist has to be available also to analyse the liver biopsy.[25, 26] We have selected only donors within our Region whose donation centers were at most 150 km far from the pathological anatomy center, thus not representing a bias when CIT was measured. This technique becomes more difficult to apply in contexts where the allocation is on larger territory. The allocation system in Italy provides national distribution only for special programs (pediatric list, emergencies, hyperimmune patients), while in other cases, also for organs from marginal donors, the allocation is regional.
Secondly, there could be the risk of not having a diagnostic biopsy when performing the ISKB. However, in our series, only in 4 cases we needed to repeat the kidney biopsies on back table as we did not have enough tissue for the sampling analysis. More importantly, no kidneys were lost for a surgical damage. The same surgical team performed the sampling of liver and kidneys. This allowed for more experienced surgeons and contributed to have few complications. Nevertheless, ISKB must be performed with care and attention in order to avoid any possible parenchymal bleeding or hematoma.
Furthermore, being a retrospective study, the two populations were different, despite the propensity score analysis should help to limit this gap. A randomized study would be ideal at this point, but our positive results do not allow us to go back from such an effective strategy. This procedure is easily executable in centres where the same surgical team provides liver and kidneys also during multiorgan procurement and could be easily widespread.
Finally, it should be mentioned that all patients underwent to ESKB were enrolled in the period 2008–2011 while those underwent ISKB in the period 2012–2017. Consequently, we were not able to adjust our estimates for the year of enrolment in the study population.
Performing pre-implantation kidney biopsy during the recovery, prior to the aortic cross-clamping, may be a strategy to reduce cold ischemia time and improve transplant outcomes.