Dr Michael Goldstein
Director, Kidney and Pancreas Transplantation Mount Sinai Medical Center Medical Director New York Organ Donor Network
The maximal utilization of deceased donor kidneys along the broad spectrum of donor quality necessitates the optimization of allograft evaluation and selection. Organ preservation techniques, including pulsatile machine preservation (PMP) and perfusate quality greatly influence organ outcomes, and improvements in this science and technology offer opportunities for expanding the donor pool.
PMP has advanced primarily for kidneys and is now beginning to develop for livers. PMP has both diagnostic and therapeutic benefits for deceased donor kidneys. In New York, our use of the LifePort® Kidney Transporter (Organ Recovery Systems) has been extensive and has governed the practice of the kidney transplant teams for the last decade. The New York Organ Donor Network pumps over 700 kidneys annually on the LifePort. The information shared in this article will describe the lessons we've learned and the data we've shared by peer review.
The diagnostic lessons learned are centered around the machine-measured renal resistance (MMRR) of the donor organ. We performed a retrospective analysis to evaluate the significance of pre transplant donor and allograft parameters in identifying risk factors that can be utilized in forecasting 1-year allograft outcomes. The donor demographics, donor type and allograft parameters such as biopsy and MMRR were correlated with the 1-year graft outcome. We found an inverse relationship between MMRR and 1-year graft survival, specifically for MMRR at 3 and 5 hours between resistance cohorts. Organs with lower MMRR after 3 hours on the LifePort had better 1-year graft survival.
We further analyzed this group to better understand the relationship between pre-transplant renal histology and MMRR, which has not previously been described. Glomerulosclerosis (GS) has typically been used by transplant teams as the most important clinical parameter for organ selection. We identified a significant correlation between machine parameters and pre-transplant allograft biopsy parameters. In our analysis, tubulointerstitial scarring (TIS) was predictive of changes in MMRR, particularly with scarring of 26–50%. Our analysis revealed that machine preservation may affect the mechanical properties of the allograft. The longer the kidneys are on the LifePort, the lower the probability of high resistance related to TIS. The ordinal regression analysis did not reveal a significant association between GS and MMRR. Based on this evidence, it is more likely that TIS is the most important histologic finding to predict renal allograft failure.
The therapeutic benefits of PMP may be even more exciting. We performed an analysis on 1067 deceased donor kidneys that were transplanted between 2007 and 2009. The organs were analyzed in cohorts by the relative contribution of machine preservation time (MPT) and cold storage time (CST) to total cold ischemia time (CIT), with the incidence of delayed graft function (DGF) as the primary endpoint. Increasing the CST component of CIT increases DGF, whereas, increasing MPT is not a factor in causing DGF for SCD and ECD kidneys. The ratio of MPT to CIT is indirectly proportional to the incidence of DGF for both SCD and ECD kidneys. The greater the MPT component of CIT, the lower the incidence of DGF, indicating that there may be a protective or resuscitative effect on the organ.
The New York Organ Donor Network, as a transplant community, have learned many lessons that we use in our practice every day. PMP provides valuable MMRR information which correlates with allograft survival and, more importantly, there is new evidence that low resistance organs have improved function at 1-year, calculated by glomerular filtration rate (GFR). Our experience shows that PMP decreases the incidence of DGF for organs with prolonged CIT, as well as improving allograft survival for organs experiencing DGF. It also ameliorates the effects of prolonged CIT. These findings offer increased opportunities for inter-regional organ sharing and could lead to the improved utilization of marginal organs.