An Update on Usage of High-Risk Donors in Liver Transplantation

The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the donor pool. Therefore, due to organ shortage, it has been substantially difficult to reduce waitlist mortality among patients awaiting LT. Thus, marginal donors such as elderly donors, steatotic donors, split liver, and donors after cardiac death (DCD), which were once not commonly used, are now considered. Furthermore, it is encouraging to see the passing of Acts, such as the HIV Organ Policy Equity (HOPE) Act, enabling further research and development in utilizing HIV grafts. Subsequently, the newer antivirals have aided in successful post-transplant period, especially for hepatitis C positive grafts. However, currently, there is no standardization, and protocols are center specific in the usage of marginal donors. Therefore, studies with longer follow ups are required to standardize its use.

Long-Term Outcomes of Kidney Transplants from Older/Marginal Donors: A Cohort Study

<b><i>Introduction:</i></b> To safely expand the donor pool, we introduced a strategy of biopsy-guided selection and allocation to single or dual transplantation of kidneys from donors &#x3e;60 years old or with hypertension, diabetes, and/or proteinuria (older/marginal donors). Here, we evaluated the long-term performance of this approach in everyday clinical practice. <b><i>Methods:</i></b> In this single-center cohort study, we compared outcomes of 98 patients who received one or two biopsy-evaluated grafts from older/marginal donors (“recipients”) and 198 patients who received nonhistologically assessed single graft from ideal donors (“reference-recipients”) from October 2004 to December 2015 at the Bergamo Transplant Center (Italy). <b><i>Results:</i></b> Older/marginal donors and their recipients were 27.9 and 19.3 years older than ideal donors and their reference-recipients, respectively. KDPI/KDRI and donor serum creatinine were higher and cold ischemia time longer in the recipient group. During a median follow-up of 51.9 (interquartile range 23.1–88.6) months, 11.2% of recipients died, 7.1% lost their graft, and 16.3% had biopsy-proven acute rejection (BPAR) versus 3.5, 7.6, and 17.7%, respectively, of reference-recipients. Overall death-censored graft failure (rate ratio 0.78 [95% CI 0.33–2.08]), 5-year death-censored graft survival (94.3% [87.8–100.0] vs. 94.2% [90.5–98.0]), BPAR incidence (rate ratio 0.87 [0.49–1.62]), and yearly measured glomerular filtration rate decline (1.18 ± 3.27 vs. 0.68 ± 2.42 mL/min/1.73 m², <i>p</i> = 0.37) were similar between recipients and reference-recipients, respectively. <b><i>Conclusions:</i></b> Biopsy-guided selection and allocation of kidneys from older/marginal donors can safely increase transplant activity in clinical practice without affecting long-term outcomes. This may help manage the growing gap between organ demand and supply without affecting long-term recipient and graft outcomes.

Histological Evaluation of Extended Criteria Donors: Donor’s Kidney Biopsy and Graft Outcome after 5 Years of Transplantation

Pre-transplant kidney biopsy is routinely used to decide whether kidneys from marginal donors should be transplanted as single or double trans-plantation. This is a 5-year extension of the follow-up of a previous study. In that study, graft outcomes were compared retrospectively between a group of 44 recipients of a single kidney graft from an extended criteria donor and a Karpinski histological score of 3 or less, and another group of 56 recipients of a single transplant with a Karpinski histological score of 4 or 5. After 5 years of transplantation, there was no difference between the two groups in terms of recipient’s serum creatinine levels (1.8 ± 0.5 vs 1.9 ± 0.6 mg/dL, P = 0.5), creatinine clearance (53 ± 23 vs 49 ± 27.0 mL/min, P = 0.6), or the rates of graft loss (41% vs 49%,P = 0.5). Therefore, the choice between single and double transplant should not be made only on the basis of histological score but should be done together with the evaluation of donor’s clinical parameters, especially the renal function.

In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve kidney preservation. This review highlights the most promising avenues of in kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.